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Kusunose M, Mifune Y, Inui A, Yamaura K, Furukawa T, Kato T, Kuroda R. Preoperative Increases in T2-Weighted Fat-Suppressed Magnetic Resonance Imaging Signal Intensities Associated With Advanced Tissue Degeneration and Mitochondrial Dysfunction in Rotator Cuff Tears. Arthroscopy 2025; 41:1705-1716. [PMID: 39214430 DOI: 10.1016/j.arthro.2024.08.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 08/08/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024]
Abstract
PURPOSE To investigate the relationship between magnetic resonance imaging (MRI) signal intensities and mitochondrial function in patients undergoing arthroscopic rotator cuff repair, assessed through histological and genetic profiling of tendon tissue. METHODS This study, conducted between April 2022 and January 2023, included 20 patients undergoing rotator cuff repair for atraumatic/degenerative tears. Rotator cuff tendon edge samples were obtained during arthroscopic rotator cuff repair. Patients were classified based on signal intensity from preoperative T2-weighted fat suppressed MRI. Specifically, they were categorized as having either high or low signal intensity at the rotator cuff tendon edge, with the deltoid muscle serving as a reference. Comparative analyses specifically compared the histological features and genetic profiles of the tendon tissue at the rotator cuff tendon edge. Histological evaluation of harvested tendon specimens during arthroscopic rotator cuff repair employed the modified Bonar score. Real-time polymerase chain reaction was used to assess expression of various mitochondrial and apoptosis-related genes. The mitochondrial morphology of the rotator cuff torn site was examined using electron microscopy. RESULTS The higher signal intensity group showed significantly higher modified Bonar scores (P = .0068), decreased mitochondrial gene expression, increased TdT-mediated dUTP-biotin nick end labeling-positive cells (P = .032), lower superoxide dismutase activity (P = .011), reduced ATP5A (P = .031), and increased cleaved caspase-9 activity (P = .026) compared with the lower signal intensity group. Electron microscopy revealed fewer mitochondrial cristae in the higher signal intensity group. CONCLUSIONS Our results suggest correlations between high MRI signal intensities and the presence of degeneration, mitochondrial dysfunction, and increased apoptosis in rotator cuff tissues. This underscores the utility of MRI signal intensity as an indicator of tissue condition. CLINICAL RELEVANCE This work builds on the premise that elevated preoperative MRI signal intensities may indicate higher rates of postoperative rotator cuff re-tears, substantiating these findings from a mitochondrial function perspective.
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Affiliation(s)
- Masaya Kusunose
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yutaka Mifune
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
| | - Atsuyuki Inui
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kohei Yamaura
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takahiro Furukawa
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tatsuo Kato
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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Luo G, Li J, Chen S, Yuan Z, Sun Z, Lou T, Chen Z, Liu H, Zhou C, Fan C, Ruan H. Polylactic acid electrospun membranes coated with chiral hierarchical-structured hydroxyapatite nanoplates promote tendon healing based on a macrophage-homeostatic modulation strategy. Bioact Mater 2025; 47:460-480. [PMID: 40034408 PMCID: PMC11872693 DOI: 10.1016/j.bioactmat.2025.01.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/30/2024] [Accepted: 01/21/2025] [Indexed: 03/05/2025] Open
Abstract
Tendon injury is a common and challenging problem in the motor system that lacks an effective treatment, affecting daily activities and lowering the quality of life. Limited tendon regenerative capability and immune microenvironment dyshomeostasis are considered the leading causes hindering tendon repair. The chirality of biomaterials was proved to dictate immune microenvironment and dramatically affect tissue repair. Herein, chiral hierarchical structure hydroxylapatite (CHAP) nanoplates are innovatively synthesized for immunomodulatory purposes and further coated onto polylactic acid electrospinning membranes to achieve long-term release for tendon regeneration adaption. Notably, levorotatory-chiral HAP (L-CHAP) nanoplates rather than dextral-chiral or racemic-chiral exhibit good biocompatibility and bioactivity. In vitro experiments demonstrate that L-CHAP induces macrophage M2 polarization by enhancing macrophage efferocytosis, which alleviates inflammatory damage to tendon stem cells (TDSCs) through downregulated IL-17-NF-κB signaling. Meanwhile, L-CHAP-mediated macrophage efferocytosis also promotes TDSCs proliferation and tenogenic differentiation. By establishing a rat model of Achilles tendon injury, L-CHAP was demonstrated to comprehensively promoting tendon repair by enhancing macrophage efferocytosis and M2 polarization in vivo, finally leading to improvement of tendon ultrastructural and mechanical properties and motor function. This novel strategy highlights the role of L-CHAP in tendon repair and thus provides a promising therapeutic strategy for tendon injury.
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Affiliation(s)
- Gang Luo
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Juehong Li
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Shuai Chen
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Zhengqiang Yuan
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Ziyang Sun
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Tengfei Lou
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Zhenyu Chen
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Hang Liu
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Chao Zhou
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Cunyi Fan
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
| | - Hongjiang Ruan
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, PR China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Building 3, Langu Science and Technology Park, Lane 70, Haiji 6th Road, Shanghai, PR China
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Planckaert G, Burssens A, Stappers F, Coudenys J, Demolder S, Kaya I, Van der Linden M, Gonçalves A, Lemeire K, Pavie B, Van Ovost E, Burssens P, Vanhaecke A, Van Dorpe J, Pringels L, Wezenbeek E, Snedeker J, De Bock K, Bonar F, Cook J, Victor J, Elewaut D, Gracey E. AI-driven histologic analysis of human Achilles tendinopathy provides a roadmap to unravel pathogenesis. Ann Rheum Dis 2025; 84:866-876. [PMID: 39922782 DOI: 10.1016/j.ard.2025.01.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 11/20/2024] [Accepted: 11/25/2024] [Indexed: 02/10/2025]
Abstract
OBJECTIVES Achilles tendinopathy is a common source of pain and dysfunction, yet its pathogenesis remains poorly understood. Research on human tendons is hampered by lack of standardisation in tissue sample validation, making interpretation of results challenging. We sought to develop an automated and operator-independent approach to histologically score human tendons. METHODS We assembled a cohort of 15 tendinopathic and 10 normal control Achilles tendon samples. We stained longitudinal sections with haematoxylin and eosin and Alcian blue and developed a low temperature epitope-retrieval protocol for immunostaining of blood vessels. Histologic sections were scored by pathologists using the current gold standard Bonar score. Whole sections were then analysed with open-source software (QuPath). Histologic features were automatically quantified across the entire section and summarised in the BonAIr score. Tissue from the same patients was subsequently analysed by quantitative polymerase chain reaction and flow cytometry to validate elements of the BonAIr score. RESULTS We observed increased cell roundness, collagen disarrangement, ground substance, and vascularity in tendinopathy using both the Bonar and BonAIr scores. Increased cellularity was only detected by the BonAIr score. Cellular and transcriptomic analyses corroborated tendinopathic shifts in all elements of the BonAIr score and further identified elevated THY1/CD90 expression in tendinopathy. CD90+ cells were found to localise to areas of low collagen alignment. These results align with the concept of stromal cell dysregulation in tendinopathy. CONCLUSIONS Automated analysis of whole tendon sections refines conventional histopathologic scoring and predicts cellular and molecular changes found in tendinopathy. The BonAIr score should be further developed for standardised assessment of tendons samples across other anatomical locations and different research centres.
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Affiliation(s)
- Guillaume Planckaert
- Unit for Molecular Immunology and Inflammation, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium; Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Orthopaedics and Traumatology, Ghent University Hospital, Ghent, Belgium
| | - Arne Burssens
- Unit for Molecular Immunology and Inflammation, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium; Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Orthopaedics and Traumatology, Ghent University Hospital, Ghent, Belgium
| | - Flore Stappers
- Unit for Molecular Immunology and Inflammation, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium; Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Julie Coudenys
- Unit for Molecular Immunology and Inflammation, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium; Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Sofía Demolder
- Unit for Molecular Immunology and Inflammation, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium; Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Irem Kaya
- Department of Pathology, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Malaïka Van der Linden
- Department of Pathology, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Amanda Gonçalves
- Bioimaging Core, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium
| | - Kelly Lemeire
- Bioimaging Core, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium
| | - Benjamin Pavie
- Bioimaging Core, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium
| | - Edwin Van Ovost
- Department of Orthopaedics and Traumatology, General Hospital (AZ) Sint-Lucas, Ghent, Belgium
| | - Peter Burssens
- Department of Orthopaedics and Traumatology, General Hospital (AZ) Jan-Palfijn, Ghent, Belgium
| | - Amber Vanhaecke
- Department of Pathology, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Jo Van Dorpe
- Department of Pathology, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Lauren Pringels
- Department of Rehabilitation Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Evi Wezenbeek
- Movement Antwerp (MOVANT) Research Group, Department of Rehabilitation Sciences and Physiotherapy (REVAKI), University of Antwerp, Wilrijk, Belgium
| | - Jess Snedeker
- Department of Health Sciences and Technology, Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland
| | - Katrien De Bock
- Department of Health Sciences and Technology, Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland
| | - Fiona Bonar
- Douglass Hanly Moir Pathology, Macquarie Park, Sydney, NSW, Australia
| | - Jill Cook
- Sport and Exercise Medicine Research Centre, La Trobe University, Melbourne, Victoria, Australia
| | - Jan Victor
- Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Orthopaedics and Traumatology, Ghent University Hospital, Ghent, Belgium
| | - Dirk Elewaut
- Unit for Molecular Immunology and Inflammation, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium; Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.
| | - Eric Gracey
- Unit for Molecular Immunology and Inflammation, Center for Inflammation Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium; Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
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Yamada Y, Torii A, Uruga Y, Sato Y, Matsubara Y, Matsumoto M, Nakamura M, Sato K, Miyamoto T. Platelet like cells differentiated from human adipose derived mesenchymal stem cells promote healing of tendinopathy in rats. Sci Rep 2025; 15:15015. [PMID: 40301586 PMCID: PMC12041348 DOI: 10.1038/s41598-025-99657-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 04/22/2025] [Indexed: 05/01/2025] Open
Abstract
Tendon and ligament disorders, such as tendinopathy, cause pain and limit levels of activities of daily living. Thus, devising methods to heal them is crucial. Although treatment with autologous platelet rich plasma (PRP) is reportedly useful against tendon injury, PRP requires blood sampling and its quality varies. Here we show that platelet-like cells (ASCL-PLCs) derived from a heterologous human adipose-derived mesenchymal stem cell line (ASCL) promote significant tendon repair in a collagenase-induced injury model in rat Achilles tendons. Single administration of human ASCL-PLCs to rat Achilles tendon after 2 weeks of collagenase treatment significantly increased tendon strength and improved semi-quantitative histological evaluation scores in 4 weeks relative to PBS-treated controls. Moreover, xeno-graft reactions were not evident in ASCL-PLC-administered rats. In vitro, ASCL-PLC treatment significantly upregulated Col1a1, Lox and Mkx gene expression in NIH3T3 fibroblasts and activated ERK signaling. Overall, ASCL-PLCs could serve as a useful tool to repair injured tendons and treat tendinopathy. This approach eliminates the need for blood sampling, ensures consistent quality, supports xeno-transplantation, and increases injured tendon strength.
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Affiliation(s)
- Yuichi Yamada
- Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
- Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Akiko Torii
- Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yukako Uruga
- Clinical and Translational Research Center, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yuiko Sato
- Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yumiko Matsubara
- Clinical and Translational Research Center, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Morio Matsumoto
- Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Masaya Nakamura
- Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Kazuki Sato
- Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Takeshi Miyamoto
- Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
- Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
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Morawski M, Krasnodębski M, Rochoń J, Kubiszewski H, Staszewski M, Kuncewicz M, Krawczyk P, Rykowski P, Bołtuć A, Lewandowski Z, Figiel W, Krawczyk M, Grąt M. Transversalis fascia collagen content and the risk of surgical complications: results of a prospective study. Langenbecks Arch Surg 2025; 410:130. [PMID: 40240627 PMCID: PMC12003564 DOI: 10.1007/s00423-025-03706-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2025] [Accepted: 04/09/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND Collagen is the major protein of the extracellular matrix that provides mechanical strength to the tissues. The relationship between the development of complications and the quality and quantity of collagen fibres has not been investigated in the literature, yet. METHODS This was a prospective study of 392 patients who underwent subcostal laparotomy for confirmed or suspected gastrointestinal malignancy. Prior to abdominal closure a sample of transversalis fascia was collected. The area covered by collagen (ACC) was measured as the mean area covered by Picosirius stained fibres in three areas of the fascia. The primary endpoint of the study was the occurrence of complications, graded according to the Clavien-Dindo over a 90-day follow-up period. RESULTS 392 patients were included in the study. A transversalis fascia sample was obtained in 354 patients (90.3%) and image assessment yielded a group of 259 specimens that were included in the analysis (66.1%). Predicting the development of complications of at least CD III based on ACC was associated with an AUC of 0.606 (p = 0.027) and an optimal threshold of 0.771. There were significantly fewer complications of at least CD III in the group of patients with ACC ≥ 0.771 (6/125) than in the group below the threshold (25/134) (p < 0.01). CONCLUSIONS Collagen content may serve as an adjunct predictor of surgical risk, although its clinical utility requires further validation. There is a need for further studies on the causal nature of this relationship and modifiable risk factors related to body collagen quality.
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Affiliation(s)
- Marcin Morawski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland.
| | - Maciej Krasnodębski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Jakub Rochoń
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Hubert Kubiszewski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Mikołaj Staszewski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Mikołaj Kuncewicz
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Piotr Krawczyk
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Paweł Rykowski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Adam Bołtuć
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Zbigniew Lewandowski
- Department of Epidemiology and Biostatistics, Medical University of Warsaw, Warsaw, Poland
| | - Wojciech Figiel
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Marek Krawczyk
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Michał Grąt
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
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Kilinc BE, Bilgin E, Eren O, Oc Y, Yilmaz B. The role of sagittal axis in biceps tenodesis for superior capsular reconstruction in massive irreparable rotator cuff tears. BMC Musculoskelet Disord 2025; 26:361. [PMID: 40229790 PMCID: PMC11995516 DOI: 10.1186/s12891-025-08615-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 04/03/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND This study aims to compare histopathological results following a 6-week postoperative follow-up of biceps tenodesis (BT) at 1/3 median, 1/3 posterior, and 1/3 anterior locations to the rotator cuff footprint (RCF) in cases of massive irreparable rotator cuff tears (MIRCT). MATERIALS AND METHODS Thirty rabbits were assigned to three groups. BT for superior capsular reconstruction (SCR) was performed on rabbits 1-10 at the 1/3 median part of the RCF along the sagittal axis using a transosseous reinforced suture with the modified Mason-Allen technique, maintaining consistent pressure in the groove (Group 1). In rabbits 11-20 (Group 2), tenodesis was performed 1/3 posterior to the RCF, while rabbits 21-30 (Group 3) underwent tenodesis 1/3 anterior to the RCF. Following the 6-week follow-up, the shoulders were excised en bloc, and histopathological evaluation was conducted using a modified Bonar's scale. Results were statistically compared among the groups. RESULTS The level of cell morphology was significantly lower in Group 2 compared to the other groups (p < 0.05). The extracellular matrix level was also significantly lower in Group 2 compared to the others (p < 0.05). There were no statistically significant differences in collagen levels across Groups 1, 2, and 3 (p > 0.05), nor in cellularity levels among the groups (p > 0.05). General score evaluation levels were significantly lower in Group 2 than in the other groups (p < 0.05). DICSUSSION BT performed on the 1/3 posterior part of the RCF demonstrated greater success compared to procedures conducted at the 1/3 median and 1/3 anterior locations for MIRCT.
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Affiliation(s)
- Bekir Eray Kilinc
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, D100 Uzeri Hastane Sok. No:1/8 34752 Icerenkoy Atasehir, Istanbul, Turkey.
| | - Emre Bilgin
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, D100 Uzeri Hastane Sok. No:1/8 34752 Icerenkoy Atasehir, Istanbul, Turkey
| | - Olcay Eren
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, D100 Uzeri Hastane Sok. No:1/8 34752 Icerenkoy Atasehir, Istanbul, Turkey
| | - Yunus Oc
- Department of Orthopedics, BHT Clinic Thema Hospital, Istanbul, Turkey
| | - Baris Yilmaz
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, D100 Uzeri Hastane Sok. No:1/8 34752 Icerenkoy Atasehir, Istanbul, Turkey
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Yoon JP, Park SJ, Kim DH, Choi YS, Lee HJ, Kim JY, Chung SW. Anti-Leukotriene Receptor Blockers Improve Tendon-Bone Interface Healing in a Rat Model of Acute Rotator Cuff Tear. Orthopedics 2025; 48:e105-e112. [PMID: 40052921 DOI: 10.3928/01477447-20250218-01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/15/2025]
Abstract
BACKGROUND Excessive expression of proinflammatory cytokines after rotator cuff (RC) surgery impairs the quality of tendon-bone interface (TBI) healing. There is evidence that the asthma drug montelukast (MS) inhibits the expression of proinflammatory cytokines. This study was conducted to verify the effect of MS administration on TBI healing after RC repair. MATERIALS AND METHODS Thirteen rats in the MS group were intraperitoneally administered 10 mg/kg of the drug daily for 2 weeks after RC surgery, and 13 rats in the control group were administered only 0.9% saline. The healing effect of the TBI was assessed through histologic and biomechanical analysis 4 weeks after tendon repair. RESULTS In the MS group, the expression of interleukin-1 beta (IL-1β; P<.01) and interleukin 6 (IL-6; P<.01) was significantly reduced compared with the control group. In the evaluation of supraspinatus fatty infiltration, the MS group showed significant inhibition of fatty infiltration compared with the control group (P<.001). Histologic analysis showed that the MS group had significant improvements in collagen density (P=.035) and alignment (P=.011). Biomechanical analysis after systemic administration of MS showed an increase in the cross-sectional area (P<.001) and elongation (P<.01) of the TBI. CONCLUSION The use of MS improved tendon elasticity through suppressing fatty infiltration and improving TBI collagen density and arrangement. The mechanism is down-regulation of IL-1β and IL-6. These results strongly support the use of MS as an anti-inflammatory agent that does not impair tendon healing. [Orthopedics. 2025;48(2):e105-e112.].
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Bühler D, Hilpert M, Barbero A, Müller AM, Müller SA, Martin I, Pelttari K. Occurrence of cellular senescence in chronic human shoulder tendinopathies and its attenuation ex vivo by inhibition of Enhancer of Zeste 2. Bone Joint Res 2025; 14:143-154. [PMID: 39996291 PMCID: PMC11851219 DOI: 10.1302/2046-3758.142.bjr-2023-0378.r2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/26/2025] Open
Abstract
Aims Our aim was to investigate occurrence of senescent cells directly in tendon tissue biopsies from patients with chronic shoulder tendinopathies, and to correlate senescence with Enhancer of zeste 2 (EZH2) expression, the functional subunit of the epigenetic master regulator polycomb repressive complex. Methods Human proximal long head of biceps tendons from patients with different chronic shoulder pathologies (n = 22), and controls from patients with humerus fracture (n = 6) and pathology (n = 4), were histologically scored for degeneration and analyzed for gene and protein expression of tendon specific factors, senescence markers, and EZH2. Tissues were further exposed to senotherapeutic compounds and the USA Food and Drugs Administration-approved selective EZH2 inhibitor EPZ-6438 and their senescence-associated secretory phenotype (SASP) assessed. Results Expression of senescence markers (CDKN2A/p16, CDKN2D/p19) and EZH2 was significantly higher in tendinopathies compared to fracture or healthy tissue controls and positively correlated with the degree of tissue degeneration. Immunofluorescent stainings demonstrated colocalization of p16 and p19 with EZH2 in tenocytes. Treatment of tendon biopsies with EPZ-6438 reduced secretion of a panel of SASP factors, including interleukin-6 (IL6), IL8, matrix metalloproteinase-3 (MMP3) or GRO1, similarly to the senotherapeutic compound AG490. Conclusion We demonstrate that senescence traits accumulate in pathological tendon tissues and positively correlate with tissue degeneration. Increased expression of CDKN2A/p16 and CDKN2D/p19 coincides with EZH2 expression, while its inhibition decreased the secretion of SASP factors, indicating a possible regulatory role of EZH2 in tenocyte senescence in tendinopathies. Reduction of cellular senescence, e.g. with EPZ-6438, opens ways to new potential therapeutic approaches for enhancing regeneration in chronic tendinopathies.
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Affiliation(s)
- Dominik Bühler
- Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
- Department of Orthopaedics and Traumatology, Basel, Switzerland
| | - Morgane Hilpert
- Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Andrea Barbero
- Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Andreas M. Müller
- Department of Orthopaedics and Traumatology, Basel, Switzerland
- Department of Surgery, University Hospital Basel, Basel, Switzerland
| | - Sebastian A. Müller
- Department of Orthopedic Surgery and Traumatology, Kantonsspital Baselland, Bruderholz, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Ivan Martin
- Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
- Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland
| | - Karoliina Pelttari
- Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
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9
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Yurteri A, Mercan N, Çelik ZE, Yaykaşlı H, Yıldırım A. Does quercetin affect tendon healing? An experimental study in a rat model of Achilles tendon injury. Front Med (Lausanne) 2025; 12:1522517. [PMID: 39975674 PMCID: PMC11835819 DOI: 10.3389/fmed.2025.1522517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 01/24/2025] [Indexed: 02/21/2025] Open
Abstract
Purpose The objective of this study was to investigate the impact of quercetin, a potent antioxidant, on tendon healing utilizing a rat Achilles tendon injury model. Materials and methods The study involved 32 male Wistar-Albino rats, randomly split into experimental (quercetin) and control groups, each with 16 rats. A bilateral Achilles tenotomy model was applied, with the experimental group receiving quercetin and the control group receiving corn oil via oral gavage from surgery until sacrifice. One Achilles tendon per rat underwent histopathological and immunohistochemical evaluations, while the other underwent biomechanical analysis. Results Tendons were evaluated histopathologically in terms of tenocyte, ground substance, collagen, and vascularity, and quercetin was observed to significantly increase tendon healing in the experimental group (p-values = 0.0232, 0.0128, 0.0272, 0.0307, respectively). In the immunohistochemical analysis, type I collagen, type III collagen, alpha smooth muscle actin (SMA), and Galectin-3 were evaluated, and it was observed that quercetin increased tendon healing (p-values = 0.0166, 0.0036, 0.0323, 0.0295, respectively). In the biomechanical analysis, the rupture strength was evaluated with six parameters (failure load, maximum energy, displacement, stiffness, ultimate stress, and strain), and it was observed that quercetin significantly increased the rupture strength (p-values = 0.032, 0.014, 0.026, 0.025, 0.045, 0.012, respectively). Conclusion Quercetin significantly enhanced tendon healing both biomechanically and immunohistochemically. However, further clinical studies are needed to understand its effects on human tendon healing, as this is the first study of its kind.
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Affiliation(s)
- Ahmet Yurteri
- Department of Orthopedics and Traumatology, Konya City Hospital, Konya, Türkiye
| | - Numan Mercan
- Department of Orthopedics and Traumatology, Kahramanmaraş Necip Fazıl City Hospital, Kahramanmaraş, Türkiye
| | | | - Hakan Yaykaşlı
- Department of Electronics, Kahramanmaraş İstiklal University, Kahramanmaraş, Türkiye
| | - Ahmet Yıldırım
- Department of Orthopedics and Traumatology, Konya City Hospital, Konya, Türkiye
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10
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Yoon JP, Park SJ, Kim DH, Choi YS, Lee HJ, Park EJJ, Cho CH, Chung SW. Ezetimibe/Atorvastatin, a Treatment for Hyperlipidemia, Inhibits Supraspinatus Fatty Infiltration and Improves Bone-Tendon Interface Healing in a Rotator Cuff Tear Rat Model. Am J Sports Med 2025; 53:80-89. [PMID: 39741475 DOI: 10.1177/03635465241299408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
BACKGROUND Multiple factors, such as muscle fatty infiltration (FI), tendon collagen content, and collagen arrangement, determine bone-tendon interface (BTI) healing after rotator cuff (RC) repair. PURPOSE To evaluate the effects of systemic administration of ezetimibe-atorvastatin (EZE/ATZ) combination on muscle FI and tendon collagen density and arrangement in an RC repair rat model. STUDY DESIGN Controlled laboratory study. METHODS A total of 26 male Sprague-Dawley rats were randomly divided equally into control and EZE/ATZ groups and subjected to RC tendon repair surgery. Postoperatively, the EZE/ATZ group rats received a combination of EZE (10 mg/kg/d) and ATZ (20 mg/kg/d) for 4 weeks, after which they were sacrificed. Oil Red O staining was used to assess FI in the supraspinatus muscle. The expression of biomarkers related to muscle atrophy and FI was measured using quantitative real-time polymerase chain reaction. For the qualitative and quantitative analysis of FI-related biomarkers, immunohistochemical staining was performed. Biomechanical and histological analyses were performed to evaluate the quality of BTI healing after RC repair. RESULTS The EZE/ATZ group showed significantly lower FI compared with the control group (P < .001) and significantly downregulated expression of gene markers related to muscle atrophy and FI. On histological analysis, the EZE/ATZ group exhibited increased collagen type I contents, consistent collagen arrangement (P = .005), and significantly higher collagen density (P = .003) compared with the control group. Biomechanical analysis of the BTI healing revealed that the EZE/ATZ group had significantly increased ultimate strength (P = .006) compared with the control group. CONCLUSION Systemic EZE/ATZ administration suppressed supraspinatus FI by downregulating muscle atrophy-related and FI-related genes after RC repair. Additionally, EZE/ATZ use improved collagen biosynthesis, density, and arrangement at the BTI and significantly increased tensile strength. CLINICAL RELEVANCE The results of the current study strongly advocate the use of EZE/ATZ to improve shoulder function and tendon healing after RC repair.
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Affiliation(s)
- Jong Pil Yoon
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Sung-Jin Park
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Dong-Hyun Kim
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Yoon Seong Choi
- Department of Carbon Hybrid Fiber Science, Kyungpook National University, Daegu, Republic of Korea
| | - Hyun Joo Lee
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Eugene Jae Jin Park
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Chul-Hyun Cho
- Department of Orthopedic Surgery, Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Seok Won Chung
- Department of Orthopaedic Surgery, Konkuk University Medical Center, Seoul, Republic of Korea
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11
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Zhang X, Li M, Mao X, Yao Z, Zhu W, Yuan Z, Gao X, Pan S, Zhang Y, Zhao J, Mao H. Small Intestinal Submucosa Hydrogel Loaded With Gastrodin for the Repair of Achilles Tendinopathy. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2401886. [PMID: 39185812 DOI: 10.1002/smll.202401886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 08/05/2024] [Indexed: 08/27/2024]
Abstract
Achilles tendinopathy (AT) is an injury caused by overuse of the Achilles tendon or sudden force on the Achilles tendon, with a considerable inflammatory infiltrate. As Achilles tendinopathy progresses, inflammation and inflammatory factors affect the remodeling of the extracellular matrix (ECM) of the tendon. Gastrodin(Gas), the main active ingredient of Astrodia has anti-inflammatory, antioxidant, and anti-apoptotic properties. The small intestinal submucosa (SIS) is a naturally decellularized extracellular matrix(dECM)material and has a high content of growth factors as well as good biocompatibility. However, the reparative effects of SIS and Gas on Achilles tendinopathy and their underlying mechanisms remain unknown. Here, it is found that SIS hydrogel loaded with gastrodin restored the mechanical strength of the Achilles tendon, facilitated ECM remodeling, and restored ordered collagen arrangement by promoting the translocation of protein synthesis. It also decreases the expression of inflammatory factors and reduces the infiltration of inflammatory cells by inhibiting the NF-κB signaling pathway. It is believed that through further research, Gas + SIS may be used in the future for the treatment of Achilles tendinopathy and other Achilles tendon injury disorders.
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Affiliation(s)
- Xiqian Zhang
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, P. R. China
| | - Mei Li
- Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, P. R. China
| | - Xufeng Mao
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, P. R. China
| | - Zheyu Yao
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, P. R. China
| | - Weilai Zhu
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, 315211, P. R. China
| | - Zheyang Yuan
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, P. R. China
| | - Xiang Gao
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, P. R. China
| | - Senghao Pan
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, 315211, P. R. China
| | - Yijun Zhang
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, 315211, P. R. China
| | - Jiyuan Zhao
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, 315211, P. R. China
| | - Haijiao Mao
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, P. R. China
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12
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Jaworski Ł, Zabrzyński J, Millett PJ, Rupp MC, Familiari F, Huri G, Erdmann J, Błachowski M, Pękala P, Gagat M. Correlation between the Long Head of the Biceps Microscopic Degeneration and Extent of Apoptotic Process. J Clin Med 2024; 13:4520. [PMID: 39124786 PMCID: PMC11313670 DOI: 10.3390/jcm13154520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024] Open
Abstract
Objectives: The purpose of this study was to determine the correlation between microscopic degeneration in the long head of the biceps tendon (LHBT) and the apoptotic process. Methods: This study included 26 consecutive patients who had undergone arthroscopic biceps tenodesis or tenotomy for symptomatic LHBT with or without concomitant rotator cuff tears (RCTs). Histological examination of the specimens under a light microscope was conducted after staining with hematoxylin, eosin, and the Alcian blue. Histopathological changes were assessed using the original Bonar score and the modified Bonar score and then correlated with the expression of the subsequent apoptosis markers: activated caspase-3 (casp3), tumor protein p53 (p53), and B-cell lymphoma 2 (BCL-2). Results: The mean original Bonar score was 8.65 (range 5-11), while the modified Bonar score was 7.61. There was no correlation between the original Bonar score and the age of the patients, but a positive correlation was found between the modified Bonar score and the age of the patients (p = 0.0022). There was no correlation between the age of patients and the expression indexes of BCL-2 and casp3. However, the expression of the p53 index showed a positive correlation with patient aging (p = 0.0441). Furthermore, there was no correlation observed between the expression of apoptotic indexes and both the original and modified Bonar scale. Conclusions: In LHB tendinopathy, the expression of apoptosis does not seem to directly correlate with the extent of degeneration, particularly in the late stages of tendinopathy. However, the transformations observed in collagen and ground substance were significantly associated with age, as well as tendinous tissue degeneration quantified according to modified Bonar score. The age of patients was also linked with the expression of the p53 index, as an increased apoptosis in the studied population.
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Affiliation(s)
- Łukasz Jaworski
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, Poland; (Ł.J.); (J.Z.); (M.B.)
| | - Jan Zabrzyński
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, Poland; (Ł.J.); (J.Z.); (M.B.)
| | - Peter J. Millett
- Steadman Philippon Research Institute, The Steadman Clinic, Vail, CO 81657, USA;
| | - Marco-Christopher Rupp
- Department of Sports Orthopaedics, Technical University of Munich, 80333 Munich, Germany;
| | - Filippo Familiari
- Department of Orthopaedic and Trauma Surgery, “Mater Domini” University Hospital, “Magna Græcia” University, 88100 Catanzaro, Italy;
| | - Gazi Huri
- Department of Orthopaedics and Traumatology, Hacettepe Universitesi, Ankara 06800, Turkey;
| | - Jakub Erdmann
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, Poland; (Ł.J.); (J.Z.); (M.B.)
| | - Michał Błachowski
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, Poland; (Ł.J.); (J.Z.); (M.B.)
| | - Przemysław Pękala
- International Evidence-Based Anatomy Working Group, Department of Anatomy, Jagiellonian University Medical College, 31-008 Krakow, Poland;
| | - Maciej Gagat
- Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland;
- Collegium Medicum, Mazovian Academy in Płock, 09-402 Płock, Poland
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13
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Yoon JP, Park SJ, Kim DH, Lee HJ, Park EJJ, Shim BJ, Chung SH, Kim JS, Chung SW. Tranexamic Acid Can Reduce Early Tendon Adhesions After Rotator Cuff Repair and Is Not Detrimental to Tendon-Bone Healing: A Comparative Animal Model Study. Arthroscopy 2024; 40:2174-2183. [PMID: 38311267 DOI: 10.1016/j.arthro.2024.01.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 01/09/2024] [Accepted: 01/12/2024] [Indexed: 02/10/2024]
Abstract
PURPOSE To determine the effects of topical tranexamic acid (TXA) administration on tendon adhesions, shoulder range of motion (ROM), and tendon healing in an acute rotator cuff repair rat model. METHODS A total of 20 Sprague Dawley rats were used. Tendon adhesion, ROM, and biomechanical and histological analysis of tendon-bone healing was conducted at 3 and 6 weeks after surgery. The rats underwent rotator cuff repair surgery on both shoulders and were administered TXA via subacromial injections. The tendon adhesion was evaluated macroscopically and histologically. Biomechanical tendon healing was measured using a universal testing machine, and histological analysis was quantified by H&E, Masson's trichrome, and picrosirius red staining. RESULTS At 3 weeks after surgery, the adhesion score was significantly lower in the TXA group (2.10 ± 0.32) than in the control group (2.70 ± 0.48) (P = .005), but there was no significant difference between the 2 groups at 6 weeks. Regarding ROM, compared with the control group, the TXA group showed significantly higher external rotation (36.35° ± 4.52° vs 28.42° ± 4.66°, P < .001) and internal rotation (45.35° ± 9.36° vs 38.94° ± 5.23°, P = .013) 3 weeks after surgery. However, at 6 weeks, there were no significant differences in external and internal rotation between the 2 groups. In the biomechanical analysis, no significant differences in gross examination (3 weeks, P = .175, 6 weeks, P = .295), load to failure (3 weeks, P = .117, 6 weeks, P = .295), or ultimate stress (3 weeks, P = .602, 6 weeks, P = .917) were noted between the 2 groups 3 and 6 weeks after surgery. In the histological analysis of tendon healing, no significant differences in the total score (3 weeks, P = .323, 6 weeks, P = .572) were found between the 2 groups 3 and 6 weeks after surgery. CONCLUSIONS Topical TXA administration showed a beneficial effect in reducing tendon adhesions and improving ROM 3 weeks postoperatively and had no effect at 6 weeks. This suggests that additional intervention with TXA may be useful in achieving long-term improvement in shoulder stiffness. Additionally, TXA may increase tissue ground substance accumulation in the late postoperative period but does not adversely affect tendon-bone interface healing. CLINICAL RELEVANCE The use of TXA after rotator cuff repair has no effect on tendon-bone interface healing in clinical practice and can improve shoulder stiffness in the early postoperative period. Additional research on the long-term effects is needed.
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Affiliation(s)
- Jong Pil Yoon
- Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Sung-Jin Park
- Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea.
| | - Dong-Hyun Kim
- Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Hyun Joo Lee
- Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Eugene Jae Jin Park
- Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Bum-Jin Shim
- Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Seung Ho Chung
- Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Jun Sung Kim
- Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Seok Won Chung
- Department of Orthopaedic Surgery, Konkuk University Medical Center, Seoul, Republic of Korea
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Zhang X, Li K, Wang C, Rao Y, Tuan RS, Wang DM, Ker DFE. Facile and rapid fabrication of a novel 3D-printable, visible light-crosslinkable and bioactive polythiourethane for large-to-massive rotator cuff tendon repair. Bioact Mater 2024; 37:439-458. [PMID: 38698918 PMCID: PMC11063952 DOI: 10.1016/j.bioactmat.2024.03.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 03/29/2024] [Accepted: 03/29/2024] [Indexed: 05/05/2024] Open
Abstract
Facile and rapid 3D fabrication of strong, bioactive materials can address challenges that impede repair of large-to-massive rotator cuff tears including personalized grafts, limited mechanical support, and inadequate tissue regeneration. Herein, we developed a facile and rapid methodology that generates visible light-crosslinkable polythiourethane (PHT) pre-polymer resin (∼30 min at room temperature), yielding 3D-printable scaffolds with tendon-like mechanical attributes capable of delivering tenogenic bioactive factors. Ex vivo characterization confirmed successful fabrication, robust human supraspinatus tendon (SST)-like tensile properties (strength: 23 MPa, modulus: 459 MPa, at least 10,000 physiological loading cycles without failure), excellent suture retention (8.62-fold lower than acellular dermal matrix (ADM)-based clinical graft), slow degradation, and controlled release of fibroblast growth factor-2 (FGF-2) and transforming growth factor-β3 (TGF-β3). In vitro studies showed cytocompatibility and growth factor-mediated tenogenic-like differentiation of mesenchymal stem cells. In vivo studies demonstrated biocompatibility (3-week mouse subcutaneous implantation) and ability of growth factor-containing scaffolds to notably regenerate at least 1-cm of tendon with native-like biomechanical attributes as uninjured shoulder (8-week, large-to-massive 1-cm gap rabbit rotator cuff injury). This study demonstrates use of a 3D-printable, strong, and bioactive material to provide mechanical support and pro-regenerative cues for challenging injuries such as large-to-massive rotator cuff tears.
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Affiliation(s)
- Xu Zhang
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, Hong Kong
| | - Ke Li
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, Hong Kong
| | - Chenyang Wang
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
| | - Ying Rao
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
| | - Rocky S. Tuan
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, Hong Kong
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
| | - Dan Michelle Wang
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, Hong Kong
- Ministry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
| | - Dai Fei Elmer Ker
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, Hong Kong
- Ministry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, Hong Kong
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15
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Kent RN, Jewett ME, Buck TP, Said M, Hold LA, Crawford EA, Killian ML, Abraham AC, Huang AH, Baker BM. Engineered Microenvironmental Cues from Fiber-Reinforced Hydrogel Composites Drive Tenogenesis and Aligned Collagen Deposition. Adv Healthc Mater 2024; 13:e2400529. [PMID: 38441411 PMCID: PMC11281874 DOI: 10.1002/adhm.202400529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Indexed: 03/25/2024]
Abstract
Effective tendon regeneration following injury is contingent on appropriate differentiation of recruited cells and deposition of mature, aligned, collagenous extracellular matrix that can withstand the extreme mechanical demands placed on the tissue. As such, myriad biomaterial approaches have been explored to provide biochemical and physical cues that encourage tenogenesis and template aligned matrix deposition in lieu of dysfunctional scar tissue formation. Fiber-reinforced hydrogels present an ideal biomaterial system toward this end given their transdermal injectability, tunable stiffness over a range amenable to tenogenic differentiation of progenitors, and capacity for modular inclusion of biochemical cues. Here, tunable and modular, fiber-reinforced, synthetic hydrogels are employed to elucidate salient microenvironmental determinants of tenogenesis and aligned collagen deposition by tendon progenitor cells. Transforming growth factor β3 drives a cell fate switch toward pro-regenerative or pro-fibrotic phenotypes, which can be biased toward the former by culture in softer microenvironments or inhibition of the RhoA/ROCK activity. Furthermore, studies demonstrate that topographical anisotropy in fiber-reinforced hydrogels critically mediates the alignment of de novo collagen fibrils, reflecting native tendon architecture. These findings inform the design of cell-free, injectable, synthetic hydrogels for tendon tissue regeneration and, likely, that of a range of load-bearing connective tissues.
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Affiliation(s)
- Robert N. Kent
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109
| | - Maggie E. Jewett
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109
| | - Trevor P. Buck
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109
| | - Mohamed Said
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109
| | - LeeAnn A. Hold
- Department of Orthopedic Surgery, University of Michigan, Ann Arbor, MI 48109
| | - Eileen A. Crawford
- Department of Orthopedic Surgery, University of Michigan, Ann Arbor, MI 48109
| | - Megan L. Killian
- Department of Orthopedic Surgery, University of Michigan, Ann Arbor, MI 48109
| | - Adam C. Abraham
- Department of Orthopedic Surgery, University of Michigan, Ann Arbor, MI 48109
| | - Alice H. Huang
- Department of Orthopedic Surgery, Columbia University, New York, NY 10027
| | - Brendon M. Baker
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109
- Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109
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Yeo YH, Jo SK, Kim MH, Lee SJ, Han SY, Park MH, Kim DY, Kim DY, Yoo IH, Kang C, Song JH, Park WH. Fabrication of atelocollagen-coated bioabsorbable suture and the evaluation of its regenerative efficacy in Achilles tendon healing using a rat experimental model. Int J Biol Macromol 2024; 271:132564. [PMID: 38782324 DOI: 10.1016/j.ijbiomac.2024.132564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/18/2024] [Accepted: 05/20/2024] [Indexed: 05/25/2024]
Abstract
Recently, the incidence of Achilles tendon ruptures (ATRs) has become more common, and repair surgery using a bioabsorbable suture is generally preferred, particularly in the case of healthy patients. Sutures composed of poly(lactic-co-glycolic acid) (PLGA) are commonly used in ATR surgeries. Nevertheless, owing to the inherent limitations of PLGA, novel bioabsorbable sutures that can accelerate Achilles tendon healing are sought. Recently, several studies have demonstrated the beneficial effects of atelocollagen on tendon healing. In this study, poly(3,4-dihydroxy-L-phenylalanine) (pDOPA), a hydrophilic biomimetic material, was used to modify the hydrophobic surface of a PLGA suture (Vicryl, VC) for the stable coating of atelocollagen on its surface. The main objective was to fabricate an atelocollagen-coated VC suture and evaluate its performance in the healing of Achilles tendon using a rat model of open repair for ATR. Structural analyses of the surface-modified suture indicated that the collagen was successfully coated on the VC/pDOPA suture. Postoperative in vivo biomechanical analysis, histological evaluation, ultrastructural/morphological analyses, and western blotting confirmed that the tendons in the VC/pDOPA/Col group exhibit superior healing than those in the VC and VC/pDOPA groups after 1 and 6 weeks following the surgery. The this study suggests that atelocollagen-coated PLGA/pDOPA sutures are preferable for future medical applications, especially in the repair of ATR.
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Affiliation(s)
- Yong Ho Yeo
- Department of Organic Materials Engineering, Chungnam National University, Daejeon, Republic of Korea
| | - Seong Kyeong Jo
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
| | - Min Hee Kim
- Department of Textile Engineering, Kyungpook National University, Republic of Korea
| | - Su Jeong Lee
- R&D planning team, Organoid Sciences Co., Ltd., 331, Pangyo-ro, Bundang-gu, Seongnam-si, Republic of Korea
| | - Seung Yun Han
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Mun Hyang Park
- Department of Pathology, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Dae Young Kim
- Department of Pathology, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Dae Yeung Kim
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
| | - In Ha Yoo
- Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chan Kang
- Department of Orthopedic Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Jae Hwang Song
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea.
| | - Won Ho Park
- Department of Organic Materials Engineering, Chungnam National University, Daejeon, Republic of Korea.
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17
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Bilgin E, Kilinc BE, Arican CD, Yilmaz B. Investigation of the pressure value while performing biceps tenodesis for superior capsuler reconstruction. J Orthop Surg Res 2024; 19:222. [PMID: 38576016 PMCID: PMC10993498 DOI: 10.1186/s13018-024-04692-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 03/19/2024] [Indexed: 04/06/2024] Open
Abstract
BACKGROUND To compare the histopathological results of biceps tenodesis (BT) performed with normal, low, and high pressures for superior capsule reconstruction (SCR) in rabbits with massive rotator cuff tears. MATERIALS AND METHODS Thirty rabbits were divided into three groups. Rabbits 1-10 underwent SCR with BT at the same pressure (Group 1), value measured in the groove; 50% lower (Group 2); 50% higher (Group 3). After the 4-week follow-up, shoulder were en-bloc excised and histopathological evaluation was performed with modified Bonar's scale. Results were compared between the groups, statistically. RESULTS Extracellular matrix were significantly lower in group 2 compared to the other groups (p < 0.05). Cellularity levels were significantly lower in group 2 compared to the other groups (p < 0.05). Group 2 had no difference between the sides (p > 0.05). Group 2 had lower vascularity levels compared to the other groups (p = 0.01). DICSUSSION When the biceps tendon was in the bicipital groove and in a more mobile state with lower pressure exposure. BT performed with a tension that creates less pressure than the biceps in the groove is more successful in SCR.
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Affiliation(s)
- Emre Bilgin
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, D100 Uzeri Hastane Sok. No:1/8 34752 Icerenkoy Atasehir, Istanbul, Turkey
| | - Bekir Eray Kilinc
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, D100 Uzeri Hastane Sok. No:1/8 34752 Icerenkoy Atasehir, Istanbul, Turkey.
| | - Cigdem Dicle Arican
- Department of Pathology, Health Sciences University, Prof. Dr. Ilhan Varank Training and Research Hospital, Istanbul, Turkey
| | - Baris Yilmaz
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, D100 Uzeri Hastane Sok. No:1/8 34752 Icerenkoy Atasehir, Istanbul, Turkey
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18
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Liu M, Zheng Q, Zheng Y, Yao Y, Wang R, Ta D, Jiang L. Combined Assessment of 2-D Ultrasound and Real-Time Shear Wave Elastography of Low-Intensity Pulsed Ultrasound Therapy Efficacy in Rabbits with Achilles Tendinopathy. ULTRASOUND IN MEDICINE & BIOLOGY 2024; 50:407-413. [PMID: 38129224 DOI: 10.1016/j.ultrasmedbio.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 11/13/2023] [Accepted: 12/01/2023] [Indexed: 12/23/2023]
Abstract
OBJECTIVE Low-intensity pulsed ultrasound (LIPUS) has been gradually used to treat Achilles tendinopathy. However, there are limited non-invasive and efficient instruments for monitoring LIPUS efficacy in Achilles tendinopathy. The purpose of this study was to assess the therapeutic effectiveness of LIPUS after Achilles tendinopathy by 2-D ultrasound and real-time shear wave elastography (SWE). METHODS Ninety New Zealand white rabbits were divided into control, sham and LIPUS groups after tendinopathy modeling. On days 1, 4, 7, 14 and 28, the Achilles tendon thickness and SWE Young's modulus on the long axis were measured. The tissues of the Achilles tendon were then evaluated histologically. RESULTS The mean SWE values increased while the average thickness and histologic scores decreased, especially in the LIPUS group (9.5% and 80.7% on day 28, respectively). The SWE values in the LIPUS group were significantly lower than those in the control group on day 1 (121.0 kPa vs. 177.6 kPa) and peaked on day 7 (173.7 kPa, p < 0.001). By day 28, the SWE value had approached that of the control (191.2 kPa vs. 192.4 kPa), and had been significantly higher than that in the sham group since day 7. SWE values and histologic scores were correlated (r = -0.792, p < 0.01). The average thickness decreased in the three groups but did not differ significantly. CONCLUSION Two-dimensional ultrasound is beneficial to the diagnosis of Achilles tendinopathy. SWE could quantify changes in Achilles tendon stiffness non-invasively during LIPUS treatment, enabling the study of early Achilles tendon healing after LIPUS treatment.
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Affiliation(s)
- Mengyao Liu
- Department of Ultrasound, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qian Zheng
- Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, China
| | - Yiwen Zheng
- Department of Ultrasound, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yijing Yao
- Department of Ultrasound, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rui Wang
- Department of Ultrasound, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dean Ta
- Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, China; Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Lixin Jiang
- Department of Ultrasound, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Zabrzyńska M, Pasiński M, Gagat M, Kułakowski M, Woźniak Ł, Elster K, Antosik P, Zabrzyński J. The Association between the Extent of the Osteoarthritic Meniscus Degeneration and Cigarette Smoking-A Pilot Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:323. [PMID: 38399610 PMCID: PMC10890507 DOI: 10.3390/medicina60020323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 01/29/2024] [Accepted: 02/01/2024] [Indexed: 02/25/2024]
Abstract
Background and Objectives: The negative effects of smoking on the musculoskeletal system were presented by many authors, although the relationship between smoking and osteoarthritis remains unclear. The aim of this paper was to investigate the negative effects of smoking on meniscal tissue in osteoarthritic knees by microscopic examination, by adapting the Bonar scoring system and its modifications. Materials and Methods: The study involved 34 patients with varus knees, from whom 65 samples of knee menisci were obtained. The mean age in the studied group was 65.385 years. The smoking status of the patients concluded that there were 13 smokers and 21 nonsmokers. Results: Among smokers, the mean classical Bonar score was 8.42 and the mean modified Bonar score was 6.65, while nonsmokers were characterized by scores of 8.51 and 7.35, respectively. There was a statistically significant negative correlation between the number of cigarettes and the collagen in the medial meniscus (p = 0.0197). Moreover, in the medial meniscus, the modified Bonar score correlated negatively with the number of cigarettes (p = 0.0180). Similarly, such a correlation was observed between the number of cigarettes and the modified Bonar score in the lateral meniscus (p = 0.04571). Furthermore, no correlation was identified between the number of cigarettes and the classical Bonar score in the lateral meniscus. There was a statistically significant difference in the collagen variable value between the smokers and nonsmokers groups (p = 0.04525). Conclusions: The microscopic investigation showed no differences in the menisci of smokers and nonsmokers, except for the collagen, which was more organized in smokers. Moreover, the modified Bonar score was correlated negatively with the number of cigarettes, which supports the role of neovascularization in meniscus pathology under the influence of tobacco smoking.
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Affiliation(s)
- Maria Zabrzyńska
- Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland
| | - Maciej Pasiński
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland; (M.P.); (J.Z.)
| | - Maciej Gagat
- Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland;
- Faculty of Medicine, Collegium Medicum, Mazovian Academy in Płock, 09-402 Płock, Poland
| | - Michał Kułakowski
- Independent Public Healthcare Center in Rypin, 87-500 Rypin, Poland; (M.K.); (K.E.)
| | - Łukasz Woźniak
- Department of Orthopaedics and Traumatology, University of Medical Sciences, 61-701 Poznan, Poland
| | - Karol Elster
- Independent Public Healthcare Center in Rypin, 87-500 Rypin, Poland; (M.K.); (K.E.)
| | - Paulina Antosik
- Department of Clinical Pathology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland;
| | - Jan Zabrzyński
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland; (M.P.); (J.Z.)
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20
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Uehara H, Itoigawa Y, Wada T, Morikawa D, Koga A, Maruyama Y, Ishijima M. Shear wave elastography correlates to degeneration and stiffness of the long head of the biceps tendon in patients undergoing tenodesis with arthroscopic shoulder surgery. J Shoulder Elbow Surg 2024; 33:e31-e41. [PMID: 37327988 DOI: 10.1016/j.jse.2023.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 04/11/2023] [Accepted: 05/06/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Tendinopathy of the long head of the biceps (LHB) tendon causes degeneration and changes its stiffness. However, a reliable means of diagnosis has not been established. Shear wave elastography (SWE) provides quantitative tissue elasticity measurements. In this study, the relationship of preoperative SWE values with biomechanically measured stiffness and degeneration of the LHB tendon tissue was investigated. METHODS LHB tendons were obtained from 18 patients who underwent arthroscopic tenodesis. SWE values were measured preoperatively at 2 sites, proximal to and within the bicipital groove of the LHB tendon. The LHB tendons were detached immediately proximal to the fixed sites and at their superior labrum insertion. Tissue degeneration was histologically quantified using the modified Bonar score. Tendon stiffness was determined using a tensile testing machine. RESULTS The SWE values of the LHB tendon were 502.1 ± 113.6 kPa proximal to the groove and 439.4 ± 123.3 kPa within the groove. The stiffness was 39.3 ± 19.2 N/mm. The SWE values displayed a moderate positive correlation with the stiffness proximal to the groove (r = 0.80) and within it (r = 0.72). The SWE value of the LHB tendon within the groove showed a moderate negative correlation with the modified Bonar score (r = -0.74). CONCLUSIONS These findings suggest that preoperative SWE values of the LHB tendon correlate moderately positively with stiffness and moderately negatively with tissue degeneration. Therefore, SWE may predict LHB tendon tissue degeneration and changes in stiffness caused by tendinopathy.
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Affiliation(s)
- Hirohisa Uehara
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan; Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yoshiaki Itoigawa
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan; Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan.
| | - Tomoki Wada
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Daichi Morikawa
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Akihisa Koga
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Yuichiro Maruyama
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Muneaki Ishijima
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan
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21
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Wang S, Yao Z, Chen L, Li J, Chen S, Fan C. Preclinical assessment of IL-1β primed human umbilical cord mesenchymal stem cells for tendon functional repair through TGF-β/IL-10 signaling. Heliyon 2023; 9:e21411. [PMID: 37954299 PMCID: PMC10638607 DOI: 10.1016/j.heliyon.2023.e21411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 10/19/2023] [Accepted: 10/20/2023] [Indexed: 11/14/2023] Open
Abstract
Background Inadequate repair capacity and disturbed immune compartments are the main pathological causes of tendinopathy. Transplantation of mesenchymal stem cells (MSCs) become an effective clinic option to alleviate tendinopathy. Interleukin-1β (IL-1β) could confer on MSCs enhanced immunoregulatory capability to remodel the repair microenvironment favoring tissue repair. Therefore, IL-1β activated UC-MSCs (1βUC-MSCs) may exert favorable efficacy in promoting tendon repair in a preclinical tendinopathy rat model. Methods Tendon-derived stem cells (TDSCs) were isolated and characterized. In vitro, the levels of immunoregulatory-related cytokines such as IL-1β, IL-6, IL-10, and TGF-β secreted by 1βUC-MSCs and unprimed UC-MSCs was measured. And tendon-specific markers expressed by TDSCs cultured with primed cultured medium (CM) or unprimed CM were detected. In vivo, Achilles tendinopathy was induced by 30 μL collagenase I injection in Sprague Dawley rats. One week later, the rats were randomly injected with UC-MSCs primed with IL-1β (106 cells per tendon), UC-MSCs, or PBS. After rats were sacrificed, histological evaluation, electron microscopy, biomechanical tests, gait performance were conducted to evaluate the structural and functional recovery of Achilles tendons. The inflammation and metabolic state of the extracellular matrix, and the potential mechanism were assessed by immunohistochemical staining and Western blot. Results UC-MSCs were activated by IL-1β to secrete higher levels of IL-10 and TGF-β while the secretion levels of IL-6 and IL-1β were not changed significantly, promoting a higher expression level of COL I and TNMD in TDSCs under proinflammatory environment. In vivo, the transplanted 1βUC-MSCs could survive up to 5 weeks after injection with tenogenic differentiation and improved tendon healing histologically semi-quantified by modified Bonar scores. This structural regeneration was further confirmed by observation of ultrastructural morphology, and led to good functional recovery including improved biomechanical properties and gait performance. During this process, the inflammatory response and metabolism of the extracellular matrix was improved through TGF-β/IL-10 pathway. Conclusion This study demonstrated that the transplantation of UC-MSCs activated by IL-1β exhibited satisfactory ability for promoting tendon functional repair in a tendinopathy rat model. During this process, the balance of inflammatory response and extracellular matrix metabolism was remodeled, and the TGF-β/Smad2/3 and IL-10 signaling pathways were activated simultaneously. We cautiously conclude that the IL-1β primed UC-MSCs could be a promising strategy for enhancing the ability of MSCs to treat tendinopathy.
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Affiliation(s)
- Shikun Wang
- Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
| | - Zhixiao Yao
- Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
| | - Lei Chen
- Department of Orthopedics, Tongji Hospital, School of Medicine Tongji University, Shanghai, China
| | - Juehong Li
- Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
| | - Shuai Chen
- Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
| | - Cunyi Fan
- Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
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22
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Öztürk TM, Özyazgan İ, Sezer G, Yalçın B, Göç R, Ülger M, Özocak H, Yakan B. Investigation of the effects of umbilical cord-derived mesenchymal stem cells and curcumin on Achilles tendon healing - can they act synergistically? ULUS TRAVMA ACIL CER 2023; 29:1218-1227. [PMID: 37889023 PMCID: PMC10771245 DOI: 10.14744/tjtes.2023.04203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 06/26/2023] [Accepted: 09/29/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND It is known that curcumin and umbilical cord-derived mesenchymal stem cells (UC-MSCs) positively affect experi-mental tendon injury healing. This study investigated individual effects and potential synergistic effects of using curcumin and UC-MSCs alone and together. METHODS Eighty female Wistar albino rats were randomly divided into five groups: Control, curcumin, sesame oil, MSCs, and Curcumin+MSCs groups. In all rats, punch tendon defect was created in both right and left Achilles tendons. While no additional treatment was applied to the control group, curcumin, sesame oil used as a solvent for curcumin, MSCs, and MSCs and curcumin com-bination were applied locally to the injury site, respectively, in the other groups. Curcumin was solved in sesame oil before application. In each group, half of the animals were euthanized in the post-operative 2nd week while the other half were euthanized in the post-operative 4th week. The right Achilles was used for biomechanical testing, while the left Achilles was used for histological evaluation and immunohistochemical analysis of type I, Type III collagen, and tenomodulin. RESULTS Histologically, significant improvement was observed in the curcumin, MSCs, and Curcumin+ MSCs groups compared to the control Group in the 2nd week. In the 2nd and 4th weeks, Type III collagen was significantly increased in the curcumin group com-pared to the control group. In week 4, tenomodulin increased significantly in the curcumin and MSCs groups compared to the control group. Tendon tensile strength increased significantly in MSCs and Curcumin+MSCs groups compared to the control group in the 4th week. No superiority was observed between the treatment groups regarding their positive effects on recovery. CONCLUSION Locally used curcumin and UC-MSCs showed positive effects that were not superior to each other in the healing of injury caused by a punch in the Achilles tendons of rats. However, synergistic effects on healing were not observed when they were applied together.
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Affiliation(s)
| | - İrfan Özyazgan
- Department of Plastic Reconstructive and Aesthetic Surgery, Erciyes University, Faculty of Medicine, Kayseri-Türkiye
| | - Gülay Sezer
- Department of Pharmacology, Erciyes University, Faculty of Medicine, Kayseri-Türkiye
| | - Betül Yalçın
- Department of Histology and Embryology, Adıyaman University, Faculty of Medicine, Adıyaman-Türkiye
| | - Rümeysa Göç
- Department of Histology and Embryology, Cumhuriyet University, Faculty of Medicine, Sivas-Türkiye
| | - Menekşe Ülger
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, Kayseri-Türkiye
| | | | - Birkan Yakan
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, Kayseri-Türkiye
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Aagaard KE, Lunsjö K, Adolfsson L, Frobell R, Björnsson Hallgren H. Factors associated with healing failure after early repair of acute, trauma-related rotator cuff tears. J Shoulder Elbow Surg 2023; 32:2074-2081. [PMID: 37178969 DOI: 10.1016/j.jse.2023.03.027] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/08/2023] [Accepted: 03/22/2023] [Indexed: 05/15/2023]
Abstract
BACKGROUND Healing failure after rotator cuff repair is a challenging problem. Acute, trauma-related tears are considered a separate entity and are often treated surgically. The aim of this study was to identify factors associated with healing failure in previously asymptomatic patients with trauma-related rotator cuff tears treated with early arthroscopic repair. METHODS This study included 62 consecutively recruited patients (23% women; median age, 61 years; age range, 42-75 years) with acute symptoms in a previously asymptomatic shoulder and a magnetic resonance imaging-verified full-thickness rotator cuff tear after shoulder trauma. All patients were offered, and underwent, early arthroscopic repair, during which a biopsy specimen was harvested from the supraspinatus tendon and analyzed for signs of degeneration. Of the patients, 57 (92%) completed 1-year follow-up and underwent assessment of repair integrity on magnetic resonance images according to the Sugaya classification. Risk factors for healing failure were investigated using a causal-relation diagram where age, body mass index, tendon degeneration (Bonar score), diabetes mellitus, fatty infiltration (FI), sex, smoking, tear location regarding integrity of the rotator cable, and tear size (number of ruptured tendons and tendon retraction) were included and analyzed. RESULTS Healing failure at 1 year was identified in 37% of patients (n = 21). A high degree of FI of the supraspinatus muscle (P = .01), a tear location including disruption of rotator cable integrity (P = .01), and old age (P = .03) were associated with healing failure. Tendon degeneration as determined by histopathology was not associated with healing failure at 1-year follow-up (P = .63). CONCLUSION Older age, increased FI of the supraspinatus muscle, and a tear including disruption of the rotator cable increased the risk of healing failure after early arthroscopic repair in patients with trauma-related full-thickness rotator cuff tears.
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Affiliation(s)
- Knut E Aagaard
- Department of Orthopaedics, Helsingborg Hospital, Helsingborg, Sweden; Department of Clinical Sciences Lund/Clinical Sciences Helsingborg, Lund University, Lund, Sweden
| | - Karl Lunsjö
- Department of Orthopaedics, Helsingborg Hospital, Helsingborg, Sweden; Department of Clinical Sciences Lund/Clinical Sciences Helsingborg, Lund University, Lund, Sweden
| | - Lars Adolfsson
- Department of Orthopaedics in Linköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Richard Frobell
- Department of Clinical Sciences Lund/Clinical Sciences Helsingborg, Lund University, Lund, Sweden
| | - Hanna Björnsson Hallgren
- Department of Orthopaedics in Linköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
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Jo SK, Yoo IH, Park HY, Kang C, Han SY, Moon JH, Park WH, Yeo YH, Jun S, Yi YS, Lee SJ, Tae JY, Song JH. An Atelocollagen Injection Enhances the Healing of Nonoperatively Treated Achilles Tendon Tears: An Experimental Study in Rats. Orthop J Sports Med 2023; 11:23259671231200933. [PMID: 37868218 PMCID: PMC10586006 DOI: 10.1177/23259671231200933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 05/19/2023] [Indexed: 10/24/2023] Open
Abstract
Background There is growing interest in nonoperative treatment for the management of Achilles tendon ruptures (ATRs). However, nonoperative treatment is limited by the risk of tendon reruptures and low satisfaction rates. Recently, atelocollagen injections have been reported to have beneficial effects on tendon healing. Purpose To evaluate the beneficial effects of injected atelocollagen on Achilles tendon healing and investigate the mechanism of atelocollagen on tendon healing. Study Design Controlled laboratory study. Methods Percutaneous tenotomy of the right Achilles tendon in 66 rats was performed. The animals were equally divided into the noninjection group (NG) and the collagen injection group (CG). At 1, 3, and 6 weeks, the Achilles functional index, cross-sectional area, load to failure, stiffness, stress, and the modified Bonar score were assessed. Transmission electron microscopy, western blotting, and immunohistochemistry were also performed. Results The Achilles functional index (-6.8 vs -43.0, respectively; P = .040), load to failure (42.1 vs 27.0 N, respectively; P = .049), and stiffness (18.8 vs 10.3 N/mm, respectively; P = .049) were higher in the CG than those in the NG at 3 weeks. There were no significant differences in histological scores between the 2 groups. Transmission electron microscopy analysis showed that the mean diameter of collagen fibrils in the CG was greater than that in the NG at 3 weeks (117.2 vs 72.6 nm, respectively; P < .001) and 6 weeks (202.1 vs 144.0 nm, respectively; P < .001). Western blot analysis showed that the expression of collagen type I in the CG was higher than that in the NG at 1 week (P = .005) and 6 weeks (P = .001). Conclusion An atelocollagen injection had beneficial effects on the healing of nonoperatively treated Achilles tendon injuries. The Achilles tendon of CG rats exhibited better functional, biomechanical, and morphological outcomes compared with NG rats. The molecular data indicated that the mechanism of atelocollagen injections may be associated with an increased amount of collagen type I. Clinical Relevance An atelocollagen injection might be a good adjuvant option for the nonoperative treatment of ATRs.
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Affiliation(s)
- Seong Kyeong Jo
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
| | - In Ha Yoo
- Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyeon Yeong Park
- Department of Occupational Therapy, College of Medical Science, Konyang University, Daejeon, Republic of Korea
| | - Chan Kang
- Department of Orthopedic Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Seung Yun Han
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Ji Hyun Moon
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Won Ho Park
- Department of Organic Materials Engineering, Chungnam National University, Daejeon, Republic of Korea
| | - Yong Ho Yeo
- Department of Organic Materials Engineering, Chungnam National University, Daejeon, Republic of Korea
| | - Sangmi Jun
- Center for Research Equipment, Korea Basic Science Institute, Daejeon, Republic of Korea
| | - Yoon-Sun Yi
- Center for Research Equipment, Korea Basic Science Institute, Daejeon, Republic of Korea
| | - Su Jeong Lee
- Department of Microbiology, School of Medicine, CHA University, Seongnam, Republic of Korea
| | - Jung Yeon Tae
- Department of Medicine, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Jae Hwang Song
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
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Credille KT, Wang ZRC, Horner NS, Regan DP, Gadomski BC, Easley JT, Garrigues GE, Yanke AB. Biphasic Interpositional Allograft for Rotator Cuff Repair Augmentation Is Safe in an Ovine Model. Arthroscopy 2023; 39:1983-1997. [PMID: 37001743 DOI: 10.1016/j.arthro.2023.03.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 03/04/2023] [Accepted: 03/09/2023] [Indexed: 04/20/2023]
Abstract
PURPOSE To perform a preclinical histologic assessment of a biphasic acellular interpositional cancellous allograft in an ovine model of rotator cuff repair (RCR) designed to better understand its safety profile and effects on tendon healing after RCR. METHODS Thirty skeletally mature sheep with clinically normal shoulders with an artificially created degenerative infraspinatus tendon tear were randomized to control and treatment groups. Animals were euthanized at 3 weeks, 6 weeks, and 12 weeks. After gross dissection, rotator cuff specimens were fixed with formalin and polymerized for sectioning and staining. Blinded histologic scores evaluated inflammatory cell infiltrates, signs of degradation, particulate debris, collagen arrangement, neovascularization, and enthesis qualitative measures. RESULTS There were no treatment specimens that exhibited histologic signs of a significant infection, inflammatory infiltrate, or foreign body reaction such as granuloma or fibrous capsule formation. Histologic scores in all categories were not significantly different at all time points, including the primary end point mean cumulative inflammatory score (control: 3.66 ± 1.21 vs treated: 4.33 ± 1.51, P = .42), when comparing the treatment and control RCR groups. In general, the degree of tendon healing and host tissue response was essentially equivalent between the 2 groups with observation of low overall levels of inflammation and progressive improvements in collagen organization, reduced tenocyte activity, and fibrocartilaginous enthesis reformation. CONCLUSIONS This histologic study demonstrated the use of a biphasic interpositional allograft for RCR augmentation in an ovine model does not generate an inflammatory response or foreign body reaction. Use of the biphasic interpositional allograft resulted in a histological profile that was essentially equivalent to that of a standard RCR at 3-, 6-, and 12-week postoperative timepoints. These findings suggest that a biphasic interpositional allograft is safe for further clinical investigation in humans before broader clinical application. CLINICAL RELEVANCE Patch augmentation of RCR is a popular technique that has shown clinical success in improving the likelihood of a successful repair in patients at elevated risk for retear. Newer augmentation technologies are being developed to address the biology at the interface between the bone and soft tissue where failure typically occurs.
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Affiliation(s)
- Kevin T Credille
- Midwest Orthopedics at Rush University Medical Center, Chicago, Illinois
| | - Zachary R C Wang
- Midwest Orthopedics at Rush University Medical Center, Chicago, Illinois
| | - Nolan S Horner
- Midwest Orthopedics at Rush University Medical Center, Chicago, Illinois
| | - Daniel P Regan
- Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, U.S.A
| | - Benjamin C Gadomski
- Orthopaedic Bioengineering Research Laboratory, Department of Mechanical Engineering, Colorado State University, Fort Collins, Colorado, U.S.A
| | - Jeremiah T Easley
- Preclinical Surgical Research Laboratory, Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, U.S.A
| | - Grant E Garrigues
- Midwest Orthopedics at Rush University Medical Center, Chicago, Illinois
| | - Adam B Yanke
- Midwest Orthopedics at Rush University Medical Center, Chicago, Illinois.
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26
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Chuang HC, Hong CK, Hsu KL, Kuan FC, Chen Y, Yen JZ, Chiang CH, Chang HM, Su WR. Association of Coracoacromial Ligament Degeneration With Rotator Cuff Tear Patterns and Retear Rate. Orthop J Sports Med 2023; 11:23259671231175873. [PMID: 37347016 PMCID: PMC10280534 DOI: 10.1177/23259671231175873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 02/26/2023] [Indexed: 06/23/2023] Open
Abstract
Background Coracoacromial ligament (CAL) degeneration is thought to be a factor in external impingement in bursal-sided rotator cuff tears, but CAL release is associated with adverse effects. Purpose To investigate the association between CAL degeneration and the patterns of massive rotator cuff tears using multiple modalities and to assess the effect of CAL degeneration on supraspinatus tendon retear rates. Study Design Cohort study; Level of evidence, 2. Methods The authors prospectively recruited 44 patients who had undergone arthroscopic rotator cuff repair without acromioplasty or CAL release. Preoperative radiographs and magnetic resonance imaging (MRI) scans were reviewed to determine acromial morphology and CAL thickness, respectively. Rotator cuff tears were categorized as isolated supraspinatus or massive (involvement of ≥2 tendons), with massive tears categorized using the Collin classification. Acromial degeneration was analyzed using the Copeland-Levy classification. The CAL was biopsied intraoperatively and histologically analyzed using the Bonar score. At 6-month follow-up, the integrity of the repaired supraspinatus tendon was analyzed on MRI using the Sugaya classification. Finally, the associations among CAL degeneration, rotator cuff tear pattern, and arthroscopic grading were investigated. Results Patients with Collin type B rotator cuff tear had significantly higher CAL Bonar scores than those with Collin type A or isolated supraspinatus tears (10.0 vs 6.8 and 3.4; P = .03 and P < .001, respectively). Patients with a degenerative acromial undersurface of Copeland-Levy stage 2 or 3 had CALs with significantly higher Bonar scores than those with an intact acromial undersurface (8.4 and 8.2 vs 3.5; P = .034 and P = .027, respectively). The CAL Bonar scores of patients with different stages of the 6-month postoperative Sugaya classification were comparable (6.5, 7.2, 8.0, and 7.8 for stages 1, 2, 3, and 4, respectively; P = .751). Conclusion CAL degeneration was more severe in anterosuperior-type massive rotator cuff tears. Interestingly, even without acromioplasty, the severity of CAL degeneration did not affect the retear rate of the supraspinatus tendon.
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Affiliation(s)
- Hao-Chun Chuang
- Department of Orthopaedic Surgery,
National Cheng Kung University Hospital, College of Medicine, National Cheng Kung
University, Tainan
| | - Chih-Kai Hong
- Department of Orthopaedic Surgery,
National Cheng Kung University Hospital, College of Medicine, National Cheng Kung
University, Tainan
| | - Kai-Lan Hsu
- Department of Orthopaedic Surgery,
National Cheng Kung University Hospital, College of Medicine, National Cheng Kung
University, Tainan
- Department of Biomedical Engineering,
National Cheng Kung University, Tainan
| | - Fa-Chuan Kuan
- Department of Orthopaedic Surgery,
National Cheng Kung University Hospital, College of Medicine, National Cheng Kung
University, Tainan
- Department of Biomedical Engineering,
National Cheng Kung University, Tainan
| | - Yueh Chen
- Department of Orthopaedic Surgery, Sin
Lau Christian Hospital, Tainan
- Institute of Allied Health Sciences,
College of Medicine, National Cheng Kung University, Tainan
| | - Joe-Zhi Yen
- Department of Orthopaedic Surgery,
National Cheng Kung University Hospital, College of Medicine, National Cheng Kung
University, Tainan
| | - Chen-Hao Chiang
- Department of Biomedical Engineering,
National Cheng Kung University, Tainan
- Department of Orthopaedics, Ditmanson
Medical Foundation Chia-Yi Christian Hospital, Chiayi
| | - Hao-Ming Chang
- Tainan Municipal Hospital (managed by
Show Chwan Medical Care Corporation), Tainan
| | - Wei-Ren Su
- Department of Orthopaedic Surgery,
National Cheng Kung University Hospital, College of Medicine, National Cheng Kung
University, Tainan
- Medical Device R&D Core Laboratory,
National Cheng Kung University Hospital, Tainan
- Musculoskeletal Research Center,
Innovation Headquarter, National Cheng Kung University, Tainan
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27
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Johnson JW, von Stade D, Gadomski B, Easley J, Nelson B, Bisazza K, Regan D, Troyer K, Zhou T, McGilvray K. Modified Alendronate Mitigates Mechanical Degradation of the Rotator Cuff in an Osteoporotic Ovine Model. Am J Sports Med 2022; 50:3649-3659. [PMID: 36259712 DOI: 10.1177/03635465221125175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Osteoporosis is an independent risk factor for failure after arthroscopic rotator cuff repair. Since rerupture rates after rotator cuff repair are associated with decreased bone mineral density and bone microarchitecture, adaptations of biomechanical properties of the rotator cuff enthesis in patients with osteoporosis remain unclear. Additionally, the effects of osteogenic therapy carrier drugs used for the treatment of osteoporosis on rotator cuff structure and properties have not been previously documented. PURPOSE To investigate the changes to soft tissue biomechanics and insertional structure secondary to osteoporosis with and without an osteogenic therapy carrier (ie, modified alendronate). STUDY DESIGN Controlled laboratory study. METHODS Biomechanical, histopathological, and microcomputed tomography analyses were performed on 20 shoulders obtained from 10 osteoporotic sheep randomly allocated to modified bisphosphonate (ie, alendronate) or control (ie, osteoporotic without treatment) groups; 6 shoulders from healthy sheep were utilized for comparison purposes. RESULTS Tendons from the control group exhibited a 57% decrease in undeformed Young modulus as compared with the healthy group (P = .010). Tendons from the modified bisphosphonate treatment group exhibited a 229% increase in initial Young modulus as compared with the control group (P = .010). Marked changes within the tendon insertional organization were noted in both the control and the modified bisphosphonate treatment group samples as evidenced by increased interdigitation of the bone-mineralized fibrocartilaginous junction. The control samples exhibited a markedly paucicellular insertion, whereas the modified bisphosphonate treated tendons exhibited a hypercellular insertional region as compared with the healthy group. Both groups exhibited significantly (P < .01) decreased bone quality underlying the infraspinatus insertion, as evidenced by all microcomputed tomography outcome parameters. CONCLUSION This work illuminates changes to rotator cuff tendon secondary to osteoporosis. Specifically, it revealed decreased tendon modulus and altered insertional structure in the osteoporotic samples. Secondarily, these data revealed increases in tendon modulus accompanied by increased cellularity within the tendon insertion region after systemic modified bisphosphonate injections. CLINICAL RELEVANCE Bisphosphonate treatment may have a positive effect on the healing of the enthesis after rotator cuff repair.
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Affiliation(s)
- James W Johnson
- Orthopaedic Bioengineering Research Laboratory, Colorado State University, Fort Collins, Colorado, USA
| | - Devin von Stade
- Orthopaedic Bioengineering Research Laboratory, Colorado State University, Fort Collins, Colorado, USA
| | - Ben Gadomski
- Orthopaedic Bioengineering Research Laboratory, Colorado State University, Fort Collins, Colorado, USA
| | - Jeremiah Easley
- Preclinical Surgical Research Laboratory, Colorado State University, Fort Collins, Colorado, USA
| | - Brad Nelson
- Preclinical Surgical Research Laboratory, Colorado State University, Fort Collins, Colorado, USA
| | - Katie Bisazza
- Preclinical Surgical Research Laboratory, Colorado State University, Fort Collins, Colorado, USA
| | - Daniel Regan
- Flint Animal Cancer Center and Department of Microbiology, Immunology, & Pathology, Colorado State University, Fort Collins, Colorado, USA
| | - Kevin Troyer
- Orthopaedic Bioengineering Research Laboratory, Colorado State University, Fort Collins, Colorado, USA
| | - Tianjian Zhou
- Department of Statistics, Colorado State University, Fort Collins, Colorado, USA
| | - Kirk McGilvray
- Orthopaedic Bioengineering Research Laboratory, Colorado State University, Fort Collins, Colorado, USA
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Wang S, Yao Z, Zhang X, Li J, Huang C, Ouyang Y, Qian Y, Fan C. Energy-Supporting Enzyme-Mimic Nanoscaffold Facilitates Tendon Regeneration Based on a Mitochondrial Protection and Microenvironment Remodeling Strategy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2202542. [PMID: 36000796 PMCID: PMC9631092 DOI: 10.1002/advs.202202542] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 06/15/2022] [Indexed: 05/15/2023]
Abstract
Tendon injury is a tricky and prevalent motor system disease, leading to compromised daily activity and disability. Insufficient regenerative capability and dysregulation of immune microenvironment are the leading causes of functional loss. First, this work identifies persistent oxidative stress and mitochondrial impairment in the regional tendon tissues postinjury. Therefore, a smart scaffold incorporating the enzyme mimicry nanoparticle-ceria nanozyme (CeNPs) into the nanofiber bundle scaffold (NBS@CeO) with porous, anisotropic, and enhanced mechanical properties is designed to innovatively explore a targeted energy-supporting repair strategy by rescuing mitochondrial function and remodeling the microenvironment favoring endogenous regeneration. The integrated CeNPs scavenge excessive reactive oxygen species (ROS), stabilize the mitochondria membrane potential (ΔΨm), and ATP synthesis of tendon-derived stem cells (TDSCs) under oxidative stress. In a rat Achilles tendon defect model, NBS@CeO reduces oxidative damage and accelerates structural regeneration of collagen fibers, manifesting as recovering mechanical properties and motor function. Furthermore, NBS@CeO mediates the rebalance of endogenous regenerative signaling and dysregulated immune microenvironment by alleviating senescence and apoptosis of TDSCs, downregulating the secretion of senescence-associated secretory phenotype (SASP), and inducing macrophage M2 polarization. This innovative strategy highlights the role of NBS@CeO in tendon repair and thus provides a potential therapeutic approach for promoting tendon regeneration.
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Affiliation(s)
- Shikun Wang
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue RegenerationShanghai200233China
- Youth Science and Technology Innovation StudioShanghai Jiao Tong University School of MedicineShanghai200233China
| | - Zhixiao Yao
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue RegenerationShanghai200233China
- Youth Science and Technology Innovation StudioShanghai Jiao Tong University School of MedicineShanghai200233China
| | - Xinyu Zhang
- Engineering Research Center of Technical TextilesMinistry of EducationCollege of TextilesDonghua UniversityShanghai201620China
| | - Juehong Li
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue RegenerationShanghai200233China
- Youth Science and Technology Innovation StudioShanghai Jiao Tong University School of MedicineShanghai200233China
| | - Chen Huang
- Engineering Research Center of Technical TextilesMinistry of EducationCollege of TextilesDonghua UniversityShanghai201620China
| | - Yuanming Ouyang
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue RegenerationShanghai200233China
- Youth Science and Technology Innovation StudioShanghai Jiao Tong University School of MedicineShanghai200233China
| | - Yun Qian
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue RegenerationShanghai200233China
- Youth Science and Technology Innovation StudioShanghai Jiao Tong University School of MedicineShanghai200233China
| | - Cunyi Fan
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue RegenerationShanghai200233China
- Youth Science and Technology Innovation StudioShanghai Jiao Tong University School of MedicineShanghai200233China
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29
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Feasibility of Neovessel Embolization in a Large Animal Model of Tendinopathy: Safety and Efficacy of Various Embolization Agents. J Pers Med 2022; 12:jpm12091530. [PMID: 36143314 PMCID: PMC9501590 DOI: 10.3390/jpm12091530] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/12/2022] [Accepted: 09/15/2022] [Indexed: 11/17/2022] Open
Abstract
Targeting neovessels in chronic tendinopathies has emerged as a new therapeutic approach and several embolization agents have been reported. The aim of this study was to investigate the feasibility of embolization with different agents in a porcine model of patellar tendinopathy and evaluate their safety and efficacy. Eight 3-month-old male piglets underwent percutaneous injection of collagenase type I to induce patellar tendinopathies (n = 16 tendons). They were divided into four groups (2 piglets, 4 tendons/group): the control group, 50–100 µm microspheres group, 100–300 µm microspheres group, and the Imipenem/Cilastatin (IMP/CS) group. Angiography and embolization were performed for each patellar tendon on day 7 (D7). The neovessels were evaluated visually with an angiography on day 14. The pathological analysis assessed the efficacy (Bonar score, number of neovessels/mm2) and safety (off-target persistent cutaneous ischemic modifications and presence of off-target embolization agents). The technical success was 92%, with a failed embolization for one tendon due to an arterial dissection. Neoangiogenesis was significantly less important in the embolized groups compared to the control group angiographies (p = 0.04) but not with respect to histology (Bonar score p = 0.15, neovessels p = 0.07). Off-target cutaneous embolization was more frequently depicted in the histology of the 50–100 µm microspheres group (p = 0.02). Embolization of this animal model with induced patellar tendinopathy was technically feasible with different agents and allowed assessing the safety and efficacy of neovessel destruction. Particles smaller than 100 µm seemed to be associated with more complications.
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30
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Park JH, Chung SG, Jun JY, Lee JJ, Lee K. Quantitative analysis of tendon histopathology using digital pathology in rat models with Achilles tendon injury. Connect Tissue Res 2022; 63:463-474. [PMID: 34974783 DOI: 10.1080/03008207.2021.2011251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Although digital image analysis methods that quantify histopathologic features have emerged, no validated quantitative methods are available to evaluate tendon injury. This study aimed to propose and validate a quantitative analysis method to identify the histopathologic features of tendon injuries. The histopathologic features of two Achilles tendon injury models (a partial full-thickness defect model and a collagenase injection model) using Sprague-Dawley rats were evaluated by semiquantitative grading and a quantitative analysis method using a digital pathology software at weeks 1 and 4 after tendon injury (six tendons per group at each time point). The outcome variables between tendon injury models and between time points were compared, and the correlation between semiquantitative scores and the results of the quantitative analysis was investigated. The proposed analysis method quantified the severity of the histopathological features after tendon injury. Quantitative analysis differentiated the cell morphology between tendon injury models and time points better than semiquantitative scoring. The results from quantitative measurements correlated significantly with the semiquantitative scores. The proposed quantitative method can be effective in evaluating the histopathology of tendon injuries.
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Affiliation(s)
- Jae Hyeon Park
- Department of Rehabilitation Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do, Republic of Korea
| | - Sun G Chung
- Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul, Republic of Korea.,Institute of Aging, Seoul National University, Seoul, Republic of Korea
| | - Ji-Young Jun
- Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jin-Ju Lee
- Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kyoungbun Lee
- Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea
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31
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Liu Y, Deng XH, Carballo CB, Cong T, Piacentini A, Jordan Hall A, Ying L, Rodeo SA. Evaluating the role of subacromial impingement in rotator cuff tendinopathy: development and analysis of a novel rat model. J Shoulder Elbow Surg 2022; 31:1898-1908. [PMID: 35430367 DOI: 10.1016/j.jse.2022.02.041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 02/16/2022] [Accepted: 02/24/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Subacromial impingement of the rotator cuff caused by variations in acromial anatomy or altered glenohumeral kinematics leads to inflammation and degeneration of the rotator cuff, ultimately contributing to the development of tendinopathy. However, the underlying cellular and molecular changes in the impinged tendon remain poorly understood. Because the rat is an accepted model for rotator cuff studies, we have developed a rat model to study rotator cuff tendinopathy. METHODS Forty-four adult male Sprague-Dawley rats were allocated to one of 4 study groups: intact control group (group 1, n = 11); bilateral subacromial surgical clip placement to induce supraspinatus impingement for 2 weeks (group 2, n = 11), 4 weeks (group 3, n = 11), and 8 weeks (group 4, n = 11). Bilateral shoulder specimens were harvested for biomechanical testing, histology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS Radiography confirmed that all microvascular clips remained in stable position in the subacromial space. Gross inspection of supraspinatus tendon specimens in the impingement groups revealed changes in tendon morphology at the enthesis and midsubstance. Biomechanical evaluation demonstrated decreased supraspinatus tendon failure force and tissue stiffness at all time points compared with control tendons. Semiquantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 8 weeks. qRT-PCR analysis of impinged tendon specimens demonstrated upregulation of gene expression for Col3 and Mmp14 in the impingement groups compared with control groups. In muscle samples, significant upregulation was seen in the expression of genes that are commonly associated with muscle atrophy (MuRF1 and Ube2b) and fatty infiltration (Fabp4, Pparg2, and Klf15). CONCLUSION This new rat subacromial impingement model creates cellular and molecular changes consistent with the development of rotator cuff tendinopathy. The results of this study may serve as a baseline for future investigation.
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Affiliation(s)
- Yulei Liu
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA; Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Xiang-Hua Deng
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA
| | - Camila B Carballo
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA
| | - Ting Cong
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA
| | - Alexander Piacentini
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA
| | - Arielle Jordan Hall
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA
| | - Liang Ying
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA
| | - Scott A Rodeo
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA.
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32
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Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model. Int J Mol Sci 2022; 23:ijms23158170. [PMID: 35897746 PMCID: PMC9332732 DOI: 10.3390/ijms23158170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 07/22/2022] [Accepted: 07/22/2022] [Indexed: 02/01/2023] Open
Abstract
Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.
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Song JH, Kang C, Han SY, Park WH, Kim MH, Moon JH, Tae JY, Park HY, Yoo IH, Park JH, Yeo YH, Kim DY. Comparative analysis of Achilles tendon healing outcomes after open tenotomy versus percutaneous tenotomy: An experimental study in rats. J Orthop Res 2022; 40:1446-1456. [PMID: 34370341 DOI: 10.1002/jor.25159] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 06/25/2021] [Accepted: 07/30/2021] [Indexed: 02/04/2023]
Abstract
There is growing interest in conservative treatment of Achilles tendon rupture. However, the majority of experimental studies of Achilles tendon have been performed by open tenotomy. More appropriate model of conservative treatment of Achilles tendon rupture is required. We performed an experimental study to evaluate whether outcomes differ between open tenotomy and percutaneous tenotomy of the Achilles tendon in rats. The Achilles tendons of 48 rats were transected. The animals were divided into two groups according to surgical technique: open tenotomy or microscopy-assisted percutaneous tenotomy. After 1, 2, and 4 weeks, functional, biomechanical, and histological analyses were performed. Western blot was performed for quantitative molecular analysis at 1 week. The Achilles functional index was superior in the percutaneous tenotomy group, compared with the open tenotomy group, at 1 week. The cross-sectional area was significantly larger in the percutaneous tenotomy group than in the open tenotomy group at 4 weeks. Relative to the native tendons, load to failure and stiffness yielded comparable results at 2 weeks in the percutaneous tenotomy group and at 4 weeks in the open tenotomy group. The histological score was significantly better in the percutaneous tenotomy group than in the open tenotomy group at 1 week. At 1 week, interleukin-1β expression in the open tenotomy group was higher than in the percutaneous tenotomy group. In summary, Achilles tendon healing was substantially affected by the tenotomy method. We presume that our percutaneous tenotomy method might constitute a useful experimental animal model for conservative treatment of Achilles tendon rupture.
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Affiliation(s)
- Jae H Song
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
| | - Chan Kang
- Department of Orthopedic Surgery, Regional Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Seung Y Han
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Won H Park
- Department of Advanced Organic Materials and Textile Engineering System, Chungnam National University, Daejeon, Republic of Korea
| | - Min H Kim
- Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University, Indianapolis, Indiana, USA
| | - Ji H Moon
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Jung Y Tae
- Department of Medicine, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Hyeon Y Park
- Department of Occupational Therapy, Konyang University, Daejeon, Republic of Korea
| | - In H Yoo
- Department of Occupational Therapy, Konyang University, Daejeon, Republic of Korea
| | - Jong H Park
- Department of Biomedical Material, College of Medical Engineering, Konyang University, Daejeon, Republic of Korea
| | - Yong H Yeo
- Department of Advanced Organic Materials and Textile Engineering System, Chungnam National University, Daejeon, Republic of Korea
| | - Dae Y Kim
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
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Uehara H, Itoigawa Y, Wada T, Morikawa D, Koga A, Nojiri H, Kawasaki T, Maruyama Y, Ishijima M. Relationship of superoxide dismutase to rotator cuff injury/tear in a rat model. J Orthop Res 2022; 40:1006-1015. [PMID: 34185341 DOI: 10.1002/jor.25141] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 05/04/2021] [Accepted: 06/25/2021] [Indexed: 02/04/2023]
Abstract
Rotator cuff degeneration is one of the several factors that lead to rotator cuff tears. Oxidative stress and superoxide dismutase have been reported to be related to rotator cuff degeneration; however, the precise mechanism still remains unclear. In this study, we investigated the relationship of oxidative stress and superoxide dismutase to the degeneration of the rotator cuff using rat models. Eighty-four rats were used to create a collagenase-induced rotator cuff injury model (injury model) and a rotator cuff tear model (tear model). The controls were administered saline and had only a deltoid incision, respectively. We evaluated degeneration morphology of the rotator cuff using a degeneration score; dihydroethidium fluorescence intensity, which detects oxidative stress; gene expression; and superoxide dismutase activity. The rotator cuffs in the injury and tear models significantly increased degeneration scores and dihydroethidium fluorescence intensity. On the other hand, gene expression of superoxide dismutase isoform, superoxide dismutase 1, and superoxide dismutase activity were significantly decreased in the injury model but showed no significant difference in the tear model. These findings suggested that superoxide dismutase might not be associated with rotator cuff degeneration after tear but may be involved in degenerative rotator cuff without tear. However, we found that rotator cuff degeneration involves oxidative stress both with and without tear. Based on these findings, it is presumed that different treatments may be appropriate, depending on the state of rotator cuff degeneration, because the mechanisms of the degeneration may be different.
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Affiliation(s)
- Hirohisa Uehara
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan.,Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yoshiaki Itoigawa
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Tomoki Wada
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Daichi Morikawa
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Akihisa Koga
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Hidetoshi Nojiri
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Takayuki Kawasaki
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yuichiro Maruyama
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Muneaki Ishijima
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan
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Advances in Microscopic Studies of Tendinopathy: Literature Review and Current Trends, with Special Reference to Neovascularization Process. J Clin Med 2022; 11:jcm11061572. [PMID: 35329898 PMCID: PMC8949578 DOI: 10.3390/jcm11061572] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/10/2022] [Accepted: 03/11/2022] [Indexed: 01/05/2023] Open
Abstract
Tendinopathy is a process of chaotic extracellular matrix remodeling followed by increased secretion of enzymes and mediators of inflammation. The histopathological assessment of tendinous tissue is crucial to formulate the diagnosis and establish the severity of tendon degeneration. Nevertheless, the microscopic analysis of tendinous tissue features is often challenging. In this review, we aimed to compare the most popular scales used in tendon pathology assessment and reevaluate the role of the neovascularization process. The following scores were evaluated: the Bonar score, the Movin score, the Astrom and Rausing Score, and the Soslowsky score. Moreover, the role of neovascularization in tendon degeneration was reassessed. The Bonar system is the most commonly used in tendon pathology. According to the literature, hematoxylin and eosin with additional Alcian Blue staining seems to provide satisfactory results. Furthermore, two observers experienced in musculoskeletal pathology are sufficient for tendinopathy microscopic evaluation. The control, due to similar and typical alterations in tendinous tissue, is not necessary. Neovascularization plays an ambiguous role in tendon disorders. The neovascularization process is crucial in the tendon healing process. On the other hand, it is also an important component of the degeneration of tendinous tissue when the regeneration is incomplete and insufficient. The microscopic analysis of tendinous tissue features is often challenging. The assessment of tendinous tissue using the Bonar system is the most universal. The neovascularization variable in tendinopathy scoring systems should be reconsidered due to discrepancies in studies.
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de Freitas Dutra Júnior E, Hidd SMCM, Amaral MM, Filho ALMM, Assis L, Ferreira RS, Barraviera B, Martignago CCS, Figueredo-Silva J, de Oliveira RA, Tim CR. Treatment of partial injury of the calcaneus tendon with heterologous fibrin biopolymer and/or photobiomodulation in rats. Lasers Med Sci 2022; 37:971-981. [PMID: 34041619 DOI: 10.1007/s10103-021-03341-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 05/09/2021] [Indexed: 10/21/2022]
Abstract
The present study aimed to evaluate the new heterologous fibrin biopolymer associated, or not, with photobiomodulation therapy for application in tendon injuries, considered a serious and common orthopedic problem. Thus, 84 Rattus norvegicus had partial transection of the calcaneus tendon (PTCT) and were randomly divided into: control (CG); heterologous fibrin biopolymer (HFB); photobiomodulation (PBM); heterologous fibrin biopolymer + photobiomodulation (HFB + PBM). The animals received HFB immediately after PTCT, while PBM (660 nm, 40 mW, 0.23 J) started 24 h post injury and followed every 24 h for 7, 14, and 21 days. The results of the edema volume showed that after 24 h of PTCT, there was no statistical difference among the groups. After 7, 14, and 21 days, it was observed that the treatment groups were effective in reducing edema when compared to the control. The HFB had the highest edema volume reduction after 21 days of treatment. The treatment groups did not induce tissue necrosis or infections on the histopathological analysis. Tenocyte proliferation, granulation tissue, and collagen formation were observed in the PTCT area in the HFB and HFB + PBM groups, which culminated a better repair process when compared to the CG in the 3 experimental periods. Interestingly, the PBM group revealed, in histological analysis, major tendon injury after 7 days; however, in the periods of 14 and 21 days, the PBM had a better repair process compared to the CG. In the quantification of collagen, there was no statistical difference between the groups in the 3 experimental periods. The findings suggest that the HFB and PBM treatments, isolated or associated, were effective in reducing the volume of the edema, stimulating the repair process. However, the use of HFB alone was more effective in promoting the tendon repair process. Thus, the present study consolidates previous studies of tendon repair with this new HFB. Future clinical trials will be needed to validate this proposal.
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Affiliation(s)
- Enéas de Freitas Dutra Júnior
- Department of Biomedical Engineering, Instituto Científico E Tecnológico, University Brazil, Carolina FonsecaSão Paulo, 235, Brazil
| | | | - Marcello Magri Amaral
- Department of Biomedical Engineering, Instituto Científico E Tecnológico, University Brazil, Carolina FonsecaSão Paulo, 235, Brazil
| | | | - Livia Assis
- Department of Biomedical Engineering, Instituto Científico E Tecnológico, University Brazil, Carolina FonsecaSão Paulo, 235, Brazil
| | - Rui Seabra Ferreira
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, São Paulo, Brazil
| | - Benedito Barraviera
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, São Paulo, Brazil
| | | | | | - Rauirys Alencar de Oliveira
- Department of Health Sciences, Piauí State University (UESPI), Teresina, PI, Brazil
- Department of Physiotherapy, Faculdade Uninovafapi, Teresina, PI, Brazil
| | - Carla Roberta Tim
- Department of Biomedical Engineering, Instituto Científico E Tecnológico, University Brazil, Carolina FonsecaSão Paulo, 235, Brazil.
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Histopathology of long head of biceps tendon removed during tenodesis demonstrates degenerative histopathology and not inflammatory changes. BMC Musculoskelet Disord 2022; 23:185. [PMID: 35219297 PMCID: PMC8882305 DOI: 10.1186/s12891-022-05124-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 02/14/2022] [Indexed: 11/17/2022] Open
Abstract
Background The aim of this study is to describe and quantitatively analyze the histopathology of proximal long head biceps (LHB) tendinopathy in patients who have undergone LHB tenodesis. The hypothesis is that severe histopathologic changes of the LHB tendon (LHBT) will most likely be reflected with improved postoperative clinical outcomes. Methods The study included patients with isolated LHB tendinopathy or LHB tendinopathy associated with concomitant shoulder pathologies. All had failed conservative treatment (12 months) and had a positive pain response (> 50% reduction) pre-operatively after LHB tendon injection with local anesthetic. All underwent biceps tenodesis procedure between 2008 and 2014. Tendon specimens were collected and histologically analyzed with the semi-quantitative Bonar scoring system. Minimum follow-up time was 1 year. A subset of patients was retrospectively reviewed postoperatively and evaluated employing visual analogue score (VAS), short form survey (SF-12), American Shoulder and Elbow Surgeon (ASES) score, Disability of Arm, Shoulder and Hand (DASH) score, and Oxford Shoulder Score (OSS) and postoperative return to work status. Results Forty-five biceps tendon specimens were obtained from 44 patients (mean age 50 ± 9.6 years). Histopathological analyses demonstrated advanced degenerative changes with myxoid degeneration and marked collagen disorganization. Minimal inflammation was identified. There were no regional differences in histopathological changes. Clinical outcomes did not correlate significantly with severity of histopathologic changes. Conclusions This study confirms that LHBT specimens in patients undergoing tenodesis demonstrate with the use of the Bonar score histopathologic changes of chronic degeneration and not inflammation. The correct histopathologic terminology for this process is LHB tendinosis. The histopathological changes appear uniform throughout the entire length of the LHBT which may inform the nature of the procedure performed.
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No differences in histopathological degenerative changes found in acute, trauma-related rotator cuff tears compared with chronic, nontraumatic tears. Knee Surg Sports Traumatol Arthrosc 2022; 30:2521-2527. [PMID: 35133449 PMCID: PMC9206597 DOI: 10.1007/s00167-022-06884-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 01/12/2022] [Indexed: 10/25/2022]
Abstract
PURPOSE Acute trauma-related rotator cuff tears are believed to have better healing potential than chronic tears due to less degenerative changes of the tendons. However, the histopathological condition of tendons from trauma-related tears is not well investigated. The purpose of this study was to explore specific histopathological features in tendons from acute trauma-related full-thickness rotator cuff tears and to compare them to findings in tendons from nontraumatic, chronic tears. METHODS In a prospective cohort study, 62 previously asymptomatic patients [14 women, median age 61 years (range 42-75)] with trauma-related full-thickness rotator cuff tears were consecutively included. Arthroscopic repair was performed within 30 (median, IQR 25-37) days after the injury. During surgery, tissue biopsies were harvested from the supraspinatus tendons in 53 (86%) of the patients. In addition, similar biopsies were harvested from 10 patients undergoing surgery for chronic tears without history of trauma. All tissue samples were examined by a well-experienced pathologist under light microscope. Tendon degeneration was determined using the Bonar score whereas immunostaining was used for proliferation (Ki67), inflammation (CD45), apoptosis (p53) and haemosiderin staining to study traces of bleeding. RESULTS The median (IQR) Bonar score for the acute trauma-related biopsies was 10.5 (7.5-14.5) compared to 11 (5-12.8) for the control group with no statistically significant difference between the groups. No statistically significant between-group difference was found for the inflammatory index whereas tendons from patients with trauma-related full-thickness rotator cuff tears had statistically significantly higher apoptosis [3.1 (0.5-8.9) vs. 0.1 (0-1.5), p = 0.003] and proliferation [4.0 (1.8-6.9) vs. 0.4 (0-2.0), p = 0.001) indices than those undergoing surgery for chronic tears. Positive haemosiderin staining was found in 34% of tissue samples from patients with trauma-related tears compared to 10% in the control group (n.s). CONCLUSION This study suggests that there is no difference with regard to degenerative changes between supraspinatus tendons harvested from patients with acute, trauma-related rotator cuff tears and patients with nontraumatic, chronic tears. LEVEL OF EVIDENCE II.
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Ghelfi J, Bacle M, Stephanov O, de Forges H, Soulairol I, Roger P, Ferretti GR, Beregi JP, Frandon J. Collagenase-Induced Patellar Tendinopathy with Neovascularization: First Results towards a Piglet Model of Musculoskeletal Embolization. Biomedicines 2021; 10:biomedicines10010002. [PMID: 35052682 PMCID: PMC8773136 DOI: 10.3390/biomedicines10010002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 11/16/2022] Open
Abstract
Background: Therapeutic strategies targeting neovessels responsible for musculoskeletal chronic pain have emerged, including neovessels embolization. Our study aimed to develop a large animal model of patellar tendinopathy with neovascularization. Methods: Nine 3-month-old male piglets (18 patellar tendons) received percutaneous injections of increasing doses of collagenase (0 to 50 mg) at day 0 (D0). Tendinopathy was evaluated by ultrasound (D7 and D14). Neovascularization was evaluated visually and on angiographies. Bonar score was used for histological analysis (D14). Correlations were evaluated using Spearman’s rank (Rs) test. Results: Research protocol was well tolerated. All tendons were enlarged with a median increase of 31.58% [25–40.28] at D7 (p = 0.244) at D7 and 57.52% [48.41–91.45] at D14 (p = 0.065). Tendons with collagenase injection had more hypoechoic changes, with one tendon rupture (p = 0.012). Neovascularization was reported above 5 mg collagenase (p < 0.01) at D7 and D14 with dose-related neovessels induction (Rs = 0.8, p < 0.001). The Bonar score increased above 5 mg collagenase, correlated with the dose (Rs = 0.666, p = 0.003). Conclusions: The study shows the feasibility, safety and reproducibility of this new large animal model of patellar tendinopathy with neovascularization after collagenase injection. It will allow studying new treatments on direct embolization of neovessels by endovascular approach.
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Affiliation(s)
- Julien Ghelfi
- Service de Radiologie Diagnostique et Interventionnelle, CHU Grenoble Alpes, 38043 Grenoble, France; (J.G.); (G.R.F.)
- Department of Medical Imaging, Nîmes University Hospital, University of Montpellier, Medical Imaging Group Nîmes, 30000 Nimes, France; (H.d.F.); (J.-P.B.)
| | - Marylène Bacle
- Faculty of Medicine, Montpellier Nîmes University, RAM-PTNIM, 30000 Nimes, France;
| | - Olivier Stephanov
- Anatomopathology Department, Grenoble University Hospital, 38043 Grenoble, France;
| | - Hélène de Forges
- Department of Medical Imaging, Nîmes University Hospital, University of Montpellier, Medical Imaging Group Nîmes, 30000 Nimes, France; (H.d.F.); (J.-P.B.)
| | - Ian Soulairol
- Department of Pharmacy, Nîmes University Hospital, 30000 Nimes, France;
- ICGM, University of Montpellier, CNRS, ENSCM, 34090 Montpellier, France
| | - Pascal Roger
- Anatomopathology Department, Nimes University Hospital, University of Montpellier, 30000 Nimes, France;
| | - Gilbert R. Ferretti
- Service de Radiologie Diagnostique et Interventionnelle, CHU Grenoble Alpes, 38043 Grenoble, France; (J.G.); (G.R.F.)
| | - Jean-Paul Beregi
- Department of Medical Imaging, Nîmes University Hospital, University of Montpellier, Medical Imaging Group Nîmes, 30000 Nimes, France; (H.d.F.); (J.-P.B.)
| | - Julien Frandon
- Department of Medical Imaging, Nîmes University Hospital, University of Montpellier, Medical Imaging Group Nîmes, 30000 Nimes, France; (H.d.F.); (J.-P.B.)
- Correspondence: ; Tel.: +33-4-66-68-67-22
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Cho Y, Kim HS, Kang D, Kim H, Lee N, Yun J, Kim YJ, Lee KM, Kim JH, Kim HR, Hwang YI, Jo CH, Kim JH. CTRP3 exacerbates tendinopathy by dysregulating tendon stem cell differentiation and altering extracellular matrix composition. SCIENCE ADVANCES 2021; 7:eabg6069. [PMID: 34797714 PMCID: PMC8604415 DOI: 10.1126/sciadv.abg6069] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 10/01/2021] [Indexed: 05/31/2023]
Abstract
Tendinopathy, the most common disorder affecting tendons, is characterized by chronic disorganization of the tendon matrix, which leads to tendon tear and rupture. The goal was to identify a rational molecular target whose blockade can serve as a potential therapeutic intervention for tendinopathy. We identified C1q/TNF-related protein-3 (CTRP3) as a markedly up-regulated cytokine in human and rodent tendinopathy. Overexpression of CTRP3 enhanced the progression of tendinopathy by accumulating cartilaginous proteoglycans and degenerating collagenous fibers in the mouse tendon, whereas CTRP3 knockdown suppressed the tendinopathy pathogenesis. Functional blockade of CTRP3 using a neutralizing antibody ameliorated overuse-induced tendinopathy of the Achilles and rotator cuff tendons. Mechanistically, CTRP3 elicited a transcriptomic pattern that stimulates abnormal differentiation of tendon stem/progenitor cells and ectopic chondrification as an effect linked to activation of Akt signaling. Collectively, we reveal an essential role for CTRP3 in tendinopathy and propose a potential therapeutic strategy for the treatment of tendinopathy.
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Affiliation(s)
- Yongsik Cho
- Center for RNA Research, Institute for Basic Science, 08826 Seoul, South Korea
- Department of Biological Sciences, College of Natural Sciences, Seoul National University, 08826 Seoul, South Korea
| | - Hyeon-Seop Kim
- Center for RNA Research, Institute for Basic Science, 08826 Seoul, South Korea
- Department of Biological Sciences, College of Natural Sciences, Seoul National University, 08826 Seoul, South Korea
| | - Donghyun Kang
- Center for RNA Research, Institute for Basic Science, 08826 Seoul, South Korea
- Department of Biological Sciences, College of Natural Sciences, Seoul National University, 08826 Seoul, South Korea
| | - Hyeonkyeong Kim
- Center for RNA Research, Institute for Basic Science, 08826 Seoul, South Korea
- Department of Biological Sciences, College of Natural Sciences, Seoul National University, 08826 Seoul, South Korea
| | - Narae Lee
- Center for RNA Research, Institute for Basic Science, 08826 Seoul, South Korea
- Department of Biological Sciences, College of Natural Sciences, Seoul National University, 08826 Seoul, South Korea
| | - Jihye Yun
- Department of Biological Sciences, College of Natural Sciences, Seoul National University, 08826 Seoul, South Korea
- School of Medicine, CHA University, 13496 Seongnam, South Korea
| | - Yi-Jun Kim
- Institute of Convergence Medicine, Ewha Womans University Mokdong Hospital, 07985 Seoul, South Korea
| | - Kyoung Min Lee
- Foot and Ankle Division, Department of Orthopedic Surgery, Seoul National University Bundang Hospital, 13620 Seongnam, South Korea
| | - Jin-Hee Kim
- Department of Anatomy and Cell Biology, Seoul National University College of Medicine, 03080 Seoul, South Korea
| | - Hang-Rae Kim
- Department of Anatomy and Cell Biology, Seoul National University College of Medicine, 03080 Seoul, South Korea
| | - Young-il Hwang
- Department of Anatomy and Cell Biology, Seoul National University College of Medicine, 03080 Seoul, South Korea
| | - Chris Hyunchul Jo
- Department of Orthopedic Surgery, Seoul Metropolitan Government–Seoul National University (SMG-SNU) Boramae Medical Center, Seoul National University College of Medicine, 07061 Seoul, South Korea
| | - Jin-Hong Kim
- Center for RNA Research, Institute for Basic Science, 08826 Seoul, South Korea
- Department of Biological Sciences, College of Natural Sciences, Seoul National University, 08826 Seoul, South Korea
- Interdisciplinary Program in Bioinformatics, Seoul National University, 08826 Seoul, South Korea
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Kim W, Gwon Y, Kim YK, Park S, Kang SJ, Park HK, Kim MS, Kim J. Plasma-assisted multiscale topographic scaffolds for soft and hard tissue regeneration. NPJ Regen Med 2021; 6:52. [PMID: 34504097 PMCID: PMC8429553 DOI: 10.1038/s41536-021-00162-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 08/04/2021] [Indexed: 02/08/2023] Open
Abstract
The design of transplantable scaffolds for tissue regeneration requires gaining precise control of topographical properties. Here, we propose a methodology to fabricate hierarchical multiscale scaffolds with controlled hydrophilic and hydrophobic properties by employing capillary force lithography in combination with plasma modification. Using our method, we fabricated biodegradable biomaterial (i.e., polycaprolactone (PCL))-based nitrogen gas (N-FN) and oxygen gas plasma-assisted flexible multiscale nanotopographic (O-FMN) patches with natural extracellular matrix-like hierarchical structures along with flexible and controlled hydrophilic properties. In response to multiscale nanotopographic and chemically modified surface cues, the proliferation and osteogenic mineralization of cells were significantly promoted. Furthermore, the O-FMN patch enhanced regeneration of the mineralized fibrocartilage tissue of the tendon-bone interface and the calvarial bone tissue in vivo in rat models. Overall, the PCL-based O-FMN patches could accelerate soft- and hard-tissue regeneration. Thus, our proposed methodology was confirmed as an efficient approach for the design and manipulation of scaffolds having a multiscale topography with controlled hydrophilic property.
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Affiliation(s)
- Woochan Kim
- grid.14005.300000 0001 0356 9399Department of Rural and Biosystems Engineering, Chonnam National University, Gwangju, Republic of Korea ,grid.14005.300000 0001 0356 9399Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju, Republic of Korea
| | - Yonghyun Gwon
- grid.14005.300000 0001 0356 9399Department of Rural and Biosystems Engineering, Chonnam National University, Gwangju, Republic of Korea ,grid.14005.300000 0001 0356 9399Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju, Republic of Korea
| | - Yang-Kyung Kim
- grid.411597.f0000 0004 0647 2471Department of Orthopedics, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Sunho Park
- grid.14005.300000 0001 0356 9399Department of Rural and Biosystems Engineering, Chonnam National University, Gwangju, Republic of Korea ,grid.14005.300000 0001 0356 9399Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju, Republic of Korea
| | - Sung-Ju Kang
- grid.411597.f0000 0004 0647 2471Department of Orthopedics, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Hyeng-Kyu Park
- grid.411597.f0000 0004 0647 2471Department of Physical and Rehabilitation Medicine, Chonnam National University Medical School & Hospital, Gwangju, Republic of Korea
| | - Myung-Sun Kim
- grid.411597.f0000 0004 0647 2471Department of Orthopedics, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Jangho Kim
- grid.14005.300000 0001 0356 9399Department of Rural and Biosystems Engineering, Chonnam National University, Gwangju, Republic of Korea ,grid.14005.300000 0001 0356 9399Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju, Republic of Korea ,Institute of Nano-Stem Cells Therapeutics, NANOBIOSYSTEM Co., Ltd, Gwangju, 61008 Republic of Korea
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Marr N, Meeson R, Kelly EF, Fang Y, Peffers MJ, Pitsillides AA, Dudhia J, Thorpe CT. CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4. Int J Mol Sci 2021; 22:9729. [PMID: 34575887 PMCID: PMC8472220 DOI: 10.3390/ijms22189729] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/02/2021] [Accepted: 09/05/2021] [Indexed: 12/18/2022] Open
Abstract
The interfascicular matrix (IFM) binds tendon fascicles and contains a population of morphologically distinct cells. However, the role of IFM-localised cell populations in tendon repair remains to be determined. The basement membrane protein laminin-α4 also localises to the IFM. Laminin-α4 is a ligand for several cell surface receptors, including CD146, a marker of pericyte and progenitor cells. We used a needle injury model in the rat Achilles tendon to test the hypothesis that the IFM is a niche for CD146+ cells that are mobilised in response to tendon damage. We also aimed to establish how expression patterns of circulating non-coding RNAs alter with tendon injury and identify potential RNA-based markers of tendon disease. The results demonstrate the formation of a focal lesion at the injury site, which increased in size and cellularity for up to 21 days post injury. In healthy tendon, CD146+ cells localised to the IFM, compared with injury, where CD146+ cells migrated towards the lesion at days 4 and 7, and populated the lesion 21 days post injury. This was accompanied by increased laminin-α4, suggesting that laminin-α4 facilitates CD146+ cell recruitment at injury sites. We also identified a panel of circulating microRNAs that are dysregulated with tendon injury. We propose that the IFM cell niche mediates the intrinsic response to injury, whereby an injury stimulus induces CD146+ cell migration. Further work is required to fully characterise CD146+ subpopulations within the IFM and establish their precise roles during tendon healing.
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Affiliation(s)
- Neil Marr
- Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK; (N.M.); (A.A.P.)
| | - Richard Meeson
- Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, Hatfield AL9 7TA, UK; (R.M.); (E.F.K.); (J.D.)
| | - Elizabeth F. Kelly
- Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, Hatfield AL9 7TA, UK; (R.M.); (E.F.K.); (J.D.)
| | - Yongxiang Fang
- Centre for Genomic Research, Institute of Integrative Biology, Biosciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK;
| | - Mandy J. Peffers
- Institute of Ageing and Chronic Disease, University of Liverpool, Apex Building, 6 West Derby Street, Liverpool L7 9TX, UK;
| | - Andrew A. Pitsillides
- Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK; (N.M.); (A.A.P.)
| | - Jayesh Dudhia
- Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, Hatfield AL9 7TA, UK; (R.M.); (E.F.K.); (J.D.)
| | - Chavaunne T. Thorpe
- Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK; (N.M.); (A.A.P.)
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Alt E, Rothoerl R, Hoppert M, Frank HG, Wuerfel T, Alt C, Schmitz C. First immunohistochemical evidence of human tendon repair following stem cell injection: A case report and review of literature. World J Stem Cells 2021; 13:944-970. [PMID: 34367486 PMCID: PMC8316863 DOI: 10.4252/wjsc.v13.i7.944] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/29/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.
CASE SUMMARY A 66-year-old patient suffered from sPTRCT affecting the right supraspinatus and infraspinatus tendon, caused by a bicycle accident. On day 18 post injury [day 16 post magnetic resonance imaging (MRI) examination] approximately 100 g of abdominal adipose tissue was harvested by liposuction, from which approximately 75 × 106 UA-ADRCs were isolated within 2 h. Then, UA-ADRCs were injected (controlled by biplanar X-ray imaging) adjacent to the injured supraspinatus tendon immediately after isolation. Despite fast clinical recovery, a follow-up MRI examination 2.5 mo post treatment indicated the need for open revision of the injured infraspinatus tendon, which had not been treated with UA-ADRCs. During this operation, a biopsy was taken from the supraspinatus tendon at the position of the injury. A comprehensive, immunohistochemical and microscopic analysis of the biopsy (comprising 13 antibodies) was indicative of newly formed tendon tissue.
CONCLUSION Injection of UA-ADRCs can result in regeneration of injured human tendons by formation of new tendon tissue.
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Affiliation(s)
- Eckhard Alt
- Chairman of the Board, Isarklinikum Munich, Munich 80331, Germany
| | - Ralf Rothoerl
- Department of Spine Surgery, Isarklinikum Munich, Munich 80331, Germany
| | - Matthias Hoppert
- Department for Orthopedics and Trauma Surgery, Isarklinikum Munich, Munich 80331, Germany
| | - Hans-Georg Frank
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
| | - Tobias Wuerfel
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
| | - Christopher Alt
- Director of Science and Research, InGeneron GmbH, Munich 80331, Germany
| | - Christoph Schmitz
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
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Itoigawa Y, Yoshida K, Nojiri H, Morikawa D, Kawasaki T, Wada T, Koga A, Maruyama Y, Ishijima M. Association of Recurrent Tear After Arthroscopic Rotator Cuff Repair and Superoxide-Induced Oxidative Stress. Am J Sports Med 2021; 49:2048-2055. [PMID: 34015239 DOI: 10.1177/03635465211014856] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Recurrent tears after arthroscopic rotator cuff repair (ARCR) remain a significant clinical problem. Oxidative stress contributes to the degeneration of the rotator cuff, and a degenerative rotator cuff can lead to recurrent tear after ARCR. However, the correlation between oxidative stress and retear after ARCR is unclear. PURPOSE To investigate the correlation between superoxide-induced oxidative stress and recurrent tear after ARCR. STUDY DESIGN Case-control study; Level of evidence, 3. METHODS A total of 68 patients who underwent ARCR using a suture-bridge technique participated in this study. Specimens were collected from the edge of the torn tendon during surgery. The modified Bonar score was used to evaluate degeneration of the rotator cuff on histological specimens, and fluorescence intensity on dihydroethidium (DHE) staining was used to detect oxidative stress. Superoxide dismutase (SOD) enzyme activity was also measured. The following were used for clinical evaluation: age, tear size on magnetic resonance imaging (MRI) before surgery, Goutallier classification on MRI before surgery, and Japanese Orthopaedic Association score before and 6 months after surgery. After the repaired rotator cuffs were evaluated on MRI 6 months after surgery, the patients were divided into groups: those with a healed rotator cuff (healed group; n = 46) and those with a recurrent tear (retear group; n = 22). The significant differences between the groups were determined with regard to clinical evaluation, modified Bonar score, DHE intensity, and SOD activity. In addition, multivariate logistic regression analysis was performed to investigate risk factors for recurrent tear. RESULTS Age, tear size, Goutallier classification, modified Bonar score, DHE intensity, and SOD activity were significantly greater in the retear group than in the healed group, although the Japanese Orthopaedic Association score was not significantly different. Multiple logistic regression analysis demonstrated that age, tear size, and SOD activity were significantly correlated with recurrent tear. CONCLUSION In addition to tear size and age, superoxide-induced oxidative stress may be an exacerbating factor for retear after ARCR.
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Affiliation(s)
- Yoshiaki Itoigawa
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Keiichi Yoshida
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Hidetoshi Nojiri
- Department of Orthopaedic Surgery, Juntendo University, Tokyo, Japan
| | - Daichi Morikawa
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Takayuki Kawasaki
- Department of Orthopaedic Surgery, Juntendo University, Tokyo, Japan
| | - Tomoki Wada
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Akihisa Koga
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Yuichiro Maruyama
- Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Muneaki Ishijima
- Department of Orthopaedic Surgery, Juntendo University, Tokyo, Japan
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Hidd SMCM, Tim CR, Dutra EDF, Maia ALM, Assis L, Ferreira RS, Barraviera B, Silva JF, Amaral MM. Fibrin biopolymer sealant and aquatic exercise association for calcaneal tendon repair. Acta Cir Bras 2021; 36:e360407. [PMID: 34037082 PMCID: PMC8148814 DOI: 10.1590/acb360407] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 02/21/2021] [Accepted: 03/19/2021] [Indexed: 01/19/2023] Open
Abstract
PURPOSE The aim of this work was to analyze the effect of fibrin biopolymer sealant (FS) associated or not to aquatic exercise (AE) on the calcaneal tendon repair. METHODS Forty-four female Wistar rats were randomly divided into four experimental groups: Lesion control (L), Lesion and FS (LS), Lesion and AE (LE) and Lesion and FS associated to AE (LSE). The edema volume (EV), collagen ratio, and histopathological analysis were evaluated after 7, 14, and 21 days of partial tendon transection. RESULTS The EV was statistically reduced for all treatment groups after 7 and 21 days when compared to L group. The LS and LSE had the highest EV reduction after 21 days of treatment. The FS group didn't induce tissue necrosis or infections on the histopathological analysis. It was observed tenocytes proliferation, granulation tissue and collagen formation in the tendon partial transection area in the FS group. The LSE demonstrated higher amount of granulation tissue and increased the collagen deposition at the injury site. CONCLUSIONS Our data suggests that the therapeutic potential of the association of heterologous fibrin biopolymer sealant with aquatic exercise program should be further explored as it may stimulate the regeneration phase and optimize calcaneal tendon recovery.
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Affiliation(s)
| | - Carla Roberta Tim
- PhD. Universidade Brasil – Scientific and Technological Institute –
Sao Paulo (SP), Brazil
| | - Eneas de Freitas Dutra
- PhD. Universidade Estadual do Piauí – Center for Research in
Biotechnology and Biodiversity – Teresina (PI), Brazil
| | - Antônio Luiz Martins Maia
- PhD. Universidade Estadual do Piauí – Center for Research in
Biotechnology and Biodiversity – Teresina (PI), Brazil
| | - Lívia Assis
- PhD. Universidade Brasil – Scientific and Technological Institute –
Sao Paulo (SP), Brazil
| | - Rui Seabra Ferreira
- PhD. Universidade Estadual Paulista – Center for the Study of Venoms
and Venomous Animals – Botucatu (SP), Brazil
| | - Benedito Barraviera
- PhD. Universidade Estadual Paulista – Botucatu Medical School –
Botucatu (SP), Brazil
| | - José Figueiredo Silva
- PhD. Universidade Estadual do Piauí – Center for Research in
Biotechnology and Biodiversity – Teresina (PI), Brazil
| | - Marcello Magri Amaral
- PhD. Universidade Brasil – Scientific and Technological Institute –
Sao Paulo (SP), Brazil
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The Bonar Score in the Histopathological Assessment of Tendinopathy and Its Clinical Relevance-A Systematic Review. ACTA ACUST UNITED AC 2021; 57:medicina57040367. [PMID: 33918645 PMCID: PMC8069001 DOI: 10.3390/medicina57040367] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/02/2021] [Accepted: 04/06/2021] [Indexed: 12/20/2022]
Abstract
This study aimed to perform a comprehensive systematic review, which reports the role of the Bonar score in the histopathological assessment of tendinopathy and its clinical relevance. To identify all of the studies that reported relevant information on the Bonar scoring system and tendinopathy, an extensive search of the major and the most significant electronic databases (PubMed, Cochrane Central, ScienceDirect, SciELO, Web of Science) was performed. A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The extracted data included—year of study, geographical location, type of the study, radiological modifications, gender, number of patients, region of tendinopathy, mean age, control group, characteristics of the Bonar score and alterations in the scale, mean Bonar score, number of investigators, area of tendon investigation, clinical and radiological implications. An extensive search of the databases and other sources yielded a total of 807 articles. Eighteen papers were finally included in this systematic review, and of these, 13 original papers included the clinical and radiological implications of tendinopathy. Radiological evaluation was present in eight studies (both magnetic resonance imaging (MRI) and ultrasound (US)). The clinical implications were more frequent and present in 10 studies. Using the Bonar score, it is easy to quantify the pathological changes in tendinous tissue. However, its connection with clinical and radiological evaluation is much more complicated. Based on the current state of knowledge, we concluded that the neovascularization variable in the Bonar system should be reconsidered. Ideally, the microscopic assessment score should follow the established classification scale with the radiological and clinical agreement and should have a prognostic value.
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Akamatsu FE, Teodoro WR, Itezerote AM, da Silveira LKR, Saleh S, Martinez CAR, Ribeiro ML, Pereira JA, Hojaij F, Andrade M, Jacomo AL. Photobiomodulation therapy increases collagen II after tendon experimental injury. Histol Histopathol 2021; 36:663-674. [PMID: 33755188 DOI: 10.14670/hh-18-330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
A tendon is a mechanosensitive tissue that transmits muscle-derived forces to bones. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), has been used in therapeutic approaches in tendon lesions, but uncertainties regarding its mechanisms of action have prevented its widespread use. We investigated the response of PBM therapy in experimental lesions of the Achilles tendon in rats. Thirty adult male Wistar rats weighing 250 to 300 g were surgically submitted to bilateral partial transverse section of the Achilles tendon. The right tendon was treated with PBM, whereas the left tendon served as a control. On the third postoperative day, the rats were divided into three experimental groups consisting of ten rats each, which were treated with PBM (Konf, Aculas - HB 750), 780 nm and 80 mW for 20 seconds, three times/week for 7, 14 and 28 days. The rats were sacrificed at the end of the therapeutic time period. The Sca-1 was examined by immunohistochemistry and histomorphometry, and COLA1, COLA2 and COLA3 gene expression was examined by qRT-PCR. COLA2 gene expression was higher in PBM treated tendons than in the control group. The histomorphometric analysis coincided with increased number of mesenchymal cells, characterized by Sca-1 expression in the lesion region (p<0.001). PBM effectively interferes in tendon tissue repair after injury by stimulating mesenchymal cell proliferation and the synthesis of collagen type II, which is suggested to provide structural support to the interstitial tissues during the healing process of the Achilles tendon. Further studies are needed to confirm the role of PBM in tendon healing.
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Affiliation(s)
- Flávia Emi Akamatsu
- Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil.
| | - Walcy Rosolia Teodoro
- Rheumatology Division of the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, São Paulo-SP, Brazil.
| | - Ana Maria Itezerote
- Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil
| | | | - Samir Saleh
- Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil
| | - Carlos Augusto Real Martinez
- Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil
| | - Marcelo Lima Ribeiro
- Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil
| | - José Aires Pereira
- Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil
| | - Flávio Hojaij
- Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil
| | - Mauro Andrade
- Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil
| | - Alfredo Luiz Jacomo
- Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil
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Zabrzyński J, Gagat M, Łapaj Ł, Paczesny Ł, Yataganbaba A, Szwedowski D, Huri G. Relationship between long head of the biceps tendon histopathology and long-term functional results in smokers. A time to reevaluate the Bonar score? Ther Adv Chronic Dis 2021; 12:2040622321990262. [PMID: 33708369 PMCID: PMC7907713 DOI: 10.1177/2040622321990262] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 01/05/2021] [Indexed: 12/22/2022] Open
Abstract
Aim The purpose of this study was to investigate whether there is an association between smoking, the extent of the degeneration process in the biceps tendinopathy, including cells and extracellular matrix (ECM) alterations, and long-term surgical results. Methods This study comprised 40 consecutive patients admitted for shoulder arthroscopy due to symptomatic biceps tendinopathy and classified into three groups based on smoking status: active smokers, former smokers, and non-smokers. According to the classical Bonar score criteria, the histopathologic evaluation of the harvested intra-articular portion of the tendon was done. The follow-up examination was based on the American Shoulder and Elbow Surgeons Score (ASES). Results A cohort of 32 patients was enrolled in the final follow-up examination; mean 37.56 months. Histopathological evaluation according to the classical Bonar score revealed degeneration of the tendinous tissue in each group but there was no correlation between the extent of degeneration, smoking indexes and the ASES. After revision of Bonar scale within the vascularity criterion, we found a correlation between the extent of degeneration of tendinous tissue, smoking data, ASES score, and the severity of rotator cuff injury. Conclusion In this paper, we indicate the ambiguous role of the neovascularization in the biceps tendinopathy, and it was used for modification of the classical Bonar score. Consequently, recalculated, modified Bonar score was correlated positively with smoking indexes and functional outcomes. Furthermore, the morphological alterations of rotator cuff tendons also correlated positively with the extent of biceps tendon degeneration, measured according to the modified scoring system.
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Affiliation(s)
- Jan Zabrzyński
- Department of General Orthopedics, Musculoskeletal Oncology and Trauma Surgery, University of Medical Sciences, Poznan, Poland; Department of Orthopedics, Orvit Clinic, Citomed Healthcare Center, Torun, Poland
| | - Maciej Gagat
- Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Torun, Poland
| | - Łukasz Łapaj
- Department of General Orthopedics, Musculoskeletal Oncology and Trauma Surgery, University of Medical Sciences, Poznan, Poland
| | - Łukasz Paczesny
- Department of Orthopedics, Orvit Clinic, Citomed Healthcare Center, Torun, Poland
| | - Alper Yataganbaba
- Orthopedics and Traumatology Department, Hacettepe Universitesi, Ankara, Turkey
| | - Dawid Szwedowski
- Department of Orthopedics, Orvit Clinic, Citomed Healthcare Center, Torun, Poland Orthopedic Arthroscopic Surgery International (OASI) Bioresearch Foundation Milan, Italy
| | - Gazi Huri
- Orthopedics and Traumatology Department, Hacettepe Universitesi, Ankara, Turkey
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Zabrzynski J, Gagat M, Paczesny L, Grzanka D, Huri G. Correlation between smoking and neovascularization in biceps tendinopathy: a functional preoperative and immunohistochemical study. Ther Adv Chronic Dis 2020; 11:2040622320956418. [PMID: 33101619 PMCID: PMC7549321 DOI: 10.1177/2040622320956418] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 08/10/2020] [Indexed: 12/31/2022] Open
Abstract
Aims The purpose of this study was to investigate whether smoking is associated with neovascularization in the tendinopathy of the long head of the biceps tendon (LHBT). Methods The study included 40 consecutive patients who underwent arthroscopic biceps tenotomy/tenodesis due to chronic biceps tendinopathy and divided into three groups: (1) non-smokers, (2) former smokers, (3) smokers. LHBT tissue samples were stained with H&E, Alcian blue and Trichrome staining. Immunohistochemical examination was performed using anti-CD31 and anti-CD34. The neovessel density score (NDS) was scored by Bonar criteria. Results The mean period of smoking was 15.50 years with an average number of 24 cigarettes/day in the former smokers and 21.69 years with an average number of 15 cigarettes/day in the active smokers. The mean NDS was 2.23/3 in non-smokers, whereas it was 1.60/3 in former smokers and 1.31/3 in active smokers. The mean American Shoulder and Elbow Surgeons score equaled 46 in never smoked patients, 43.60 in former smokers, and 41.46 in active smokers. In the patients with smoking history, the disorganized tendinous tissue islands were avascular and composed of compact acidic polysaccharides and mucopolysaccharides. We observed negative correlation between the NDS and the smoking indexes, including cigarettes per day (p = 0.0150), smoking years (p = 0.0140), pack-years (p = 0.0088). Conclusion In conclusion, the present study revealed that smoking impairs the vascularization of the biceps tendon in chronic tendinopathy. Clinically, we observed a negative correlation between smoking and neovascularization. Furthermore, there was no correlation between neovascularization and functional preoperative status.
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Affiliation(s)
- Jan Zabrzynski
- Department of Orthopedics, Orvit Clinic, Citomed Healthcare Center, Torun, Poland
| | - Maciej Gagat
- Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Torun, Poland
| | - Lukasz Paczesny
- Department of Orthopedics, Orvit Clinic, Citomed Healthcare Center, Torun, Poland
| | - Dariusz Grzanka
- Department of Pathology, Faculty of Medicine, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Torun, Poland
| | - Gazi Huri
- Orthopedics and Traumatology Department, Hacettepe Universitesi, Ankara, Turkey
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Tranexamic acid has positive effect in early period of tendon healing by stimulating the tumor necrosis factor-alpha and matrix metalloproteinase-3 expression levels. Jt Dis Relat Surg 2020; 31:463-469. [PMID: 32962576 PMCID: PMC7607962 DOI: 10.5606/ehc.2020.74265] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Objectives
This study aims to evaluate the effect of tranexamic acid (TXA) application in tendon healing by using its immunohistochemical effects on tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-3 (MMP-3), and transforming growth factor-beta (TGF-β) expression; and to identify if TNF-α, MMP-3, and TGF-β can be used to monitor and evaluate tendon healing or not in tenotomized rat Achilles tendons. Materials and methods
Twelve male Wistar-Albino rats (age 6-7-month-old; weighing 300-350 g) were used in this retrospective study conducted between November 2016 and May 2017. The rats were divided into two groups with similar weights. The right legs of the rats were determined as the study group (TXA), and the left legs as the control serum physiologic (SP) group. Under anesthesia, bilateral Achilles tenotomy was performed and surgically repaired. 1 mL of TXA was applied locally for the right side and 1 mL of SP was locally applied for the left side. Half of the rats were sacrificed at the third week (right leg-TXA3, left leg-SP3) and the other half at sixth week (right leg-TXA6, left leg-SP6) and tendon samples were taken from the extremities. Immunohistochemical findings of TNF-α, MMP-3, and TGF-β were evaluated on the basis of the frequency and intensity of staining. Results
In TNF-α and MMP-3 and TXA groups, there was a significant difference in staining compared to SP groups (p<0.05). Regarding TNF-α expression, the total index score in the TXA6 subgroup was higher than the TXA3, SP6, and SP3 subgroups (8, 7, 3, and 4, respectively). Overall scores of TNF-α showed that TXA groups had significantly higher scores when compared to SP groups (p<0.05). In addition, total MMP-3 expression scores were significantly higher in TXA groups than in SP groups, respectively; TXA3: 14, TXA6: 11, SP3: 10, and SP6: 9 (p<0.05). However, the degree of staining with TNF-α was found to be significantly lower than MMP-3 (p<0.05). Immunohistochemical reactivity was not observed with TGF-β. Conclusion Tranexamic acid has positive effect in early period of tendon healing by stimulating the TNF-α and MMP-3 expression levels. TNF-α and MMP-3 can be used to monitor and evaluate tendon healing.
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