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Hartman H, Butler JJ, Calton M, Lin CC, Rettig S, Tishelman JC, Krebsbach S, Randall GW, Kennedy JG. Limited evidence to support demineralized bone matrix in foot and ankle surgical procedures: A systematic review. World J Orthop 2025; 16:97848. [PMID: 39850040 PMCID: PMC11752480 DOI: 10.5312/wjo.v16.i1.97848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 10/28/2024] [Accepted: 12/25/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Demineralized bone matrix (DBM) is a commonly utilized allogenic bone graft substitute to promote osseous union. However, little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures. AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures. METHODS During May 2023, the PubMed, EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies. Data regarding study characteristics, patient demographics, subjective clinical outcomes, radiological outcomes, complications, and failure rates were extracted and analyzed. In addition, the level of evidence (LOE) and quality of evidence (QOE) for each individual study was also assessed. Thirteen studies were included in this review. RESULTS In total, 363 patients (397 ankles and feet) received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8 ± 9.2 months. The most common procedure performed was ankle arthrodesis in 94 patients (25.9%). Other procedures performed included hindfoot fusion, 1st metatarsophalangeal joint arthrodesis, 5th metatarsal intramedullary screw fixation, hallux valgus correction, osteochondral lesion of the talus repair and unicameral talar cyst resection. The osseous union rate in the ankle and hindfoot arthrodesis cohort, base of the 5th metatarsal cohort, and calcaneal fracture cohort was 85.6%, 100%, and 100%, respectively. The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6 ± 0.1 to a post-operative score of 0.4 ± 0.1. The overall complication rate was 27.2%, the most common of which was non-union (8.8%). There were 43 failures (10.8%) all of which warranted a further surgical procedure. CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates. Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM, with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot. However, the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.
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Affiliation(s)
- Hayden Hartman
- Department of Medicine, Lincoln Memorial University, Knoxville, TN 37752, United States
| | - James J Butler
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY 10002, United States
| | - Megan Calton
- Department of Medicine, Royal College of Surgeons in Ireland, Dublin D02 YN77, Leinster, Ireland
| | - Charles C Lin
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY 10002, United States
| | - Samantha Rettig
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY 10002, United States
| | - Jared C Tishelman
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY 10002, United States
| | - Sebastian Krebsbach
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY 10002, United States
| | - Grace W Randall
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY 10002, United States
| | - John G Kennedy
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY 10002, United States
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Onafowokan OO, Uzosike AC, Sharma A, Galetta M, Lorentz N, Montgomery S, Fisher MR, Yung A, Tahmasebpour P, Seo L, Roberts T, Lafage R, Smith J, Jankowski PP, Sardar ZM, Shaffrey CI, Lafage V, Schoenfeld AJ, Passias PG. Treatment of adult spine deformity: A retrospective comparison of bone morphogenic protein and bone marrow aspirate with bone allograft. Acta Neurochir (Wien) 2024; 166:448. [PMID: 39528828 DOI: 10.1007/s00701-024-06346-x] [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: 08/08/2024] [Accepted: 11/03/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND : The use of bone morphogenic protein (BMP-2) in adult spine deformity (ASD) surgery remains controversial more than two decades following its approval for clinical application in spine surgery. This study was performed to assess outcomes in patients undergoing ASD surgery with BMP application compared with a combination of bone marrow aspirate, cancellous bone chips and i-Factor. METHODS This was a retrospective cohort study. ASD patients were stratified by use of intra-operative BMP (BMP +) or not (BMA + I) and surveyed for the development of complications and mechanical failure. Quality of life gained following the procedure was evaluated using quality-adjusted life years (QALYs). Cost was calculated using the PearlDiver database and CMS definitions. Multivariable analyses (ANCOVA) and logistic regression were used to adjust for confounding. RESULTS 512 patients were included (60% BMP +). At baseline, BMP + patients were older (62.5 vs 60.8 years, p < 0.010). Radiographic and quality-of-life metrics did not differ at follow up timepoints (all p > 0.05). BMP use was associated with higher supplemental rod use (OR: 7.0, 1.9 - 26.2, p = 0.004), greater number of levels fused (OR: 1.1, 1.03 - 1.17, p = 0.003) and greater neurological complications (OR: 5.0, 1.3 - 18.7, p = 0.017). Controlling for rod use and levels fused, BMP use was not associated with a lower risk of mechanical complications (OR 0.3, 95% CI: 0.2 - 3.0, p = 0.353), rod breakage (OR: 3.3, 0.6 - 18.7, p = 0.182) or implant failure (OR: 0.3, 0.04 - 1.51). At 2 years, the BMP + cohort exhibited higher overall costs ($108,062 vs $95,144, p = 0.002), comparable QALYs (0.163 vs 0.171, p = 0.65) and higher cost per QALY (p = 0.001) at two years. CONCLUSIONS In this analysis, BMP-2 application was not associated with superior outcomes when compared to a less costly biologic alternative (bone marrow aspirate + cancellous bone chips + i-Factor) following ASD surgery. The use of BMP-2 in ASD surgery appears to have reduced cost-efficacy at two years postoperatively.
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Affiliation(s)
- Oluwatobi O Onafowokan
- Duke Spine Division, Departments of Neurological and Orthopaedic Surgery, Duke School of Medicine, Durham, NC, USA
| | - Akachimere C Uzosike
- Division of Spinal Surgery/Departments of Orthopaedic and Neurosurgery, NYU Langone Medical Center, NY Spine Institute, New York, NY, USA
| | - Abhinav Sharma
- Department of Orthopedic Surgery, University of California Irvine School of Medicine, Irvine, CA, USA
| | - Matthew Galetta
- Division of Spinal Surgery/Departments of Orthopaedic and Neurosurgery, NYU Langone Medical Center, NY Spine Institute, New York, NY, USA
| | - Nathan Lorentz
- Division of Spinal Surgery/Departments of Orthopaedic and Neurosurgery, NYU Langone Medical Center, NY Spine Institute, New York, NY, USA
| | - Samuel Montgomery
- Division of Spinal Surgery/Departments of Orthopaedic and Neurosurgery, NYU Langone Medical Center, NY Spine Institute, New York, NY, USA
| | - Max R Fisher
- Duke Spine Division, Departments of Neurological and Orthopaedic Surgery, Duke School of Medicine, Durham, NC, USA
| | - Anthony Yung
- Duke Spine Division, Departments of Neurological and Orthopaedic Surgery, Duke School of Medicine, Durham, NC, USA
| | | | - Lauren Seo
- Duke Spine Division, Departments of Neurological and Orthopaedic Surgery, Duke School of Medicine, Durham, NC, USA
| | - Timothy Roberts
- Division of Spinal Surgery/Departments of Orthopaedic and Neurosurgery, NYU Langone Medical Center, NY Spine Institute, New York, NY, USA
| | - Renaud Lafage
- Department of Orthopedic Surgery, Northwell Health, Lenox Hill Hospital, New York, NY, USA
| | - Justin Smith
- Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA
| | | | - Zeeshan M Sardar
- Department of Orthopedic Surgery, Columbia University, New York, NY, USA
| | - Christopher I Shaffrey
- Duke Spine Division, Departments of Neurological and Orthopaedic Surgery, Duke School of Medicine, Durham, NC, USA
| | - Virginie Lafage
- Department of Orthopedic Surgery, Northwell Health, Lenox Hill Hospital, New York, NY, USA
| | - Andrew J Schoenfeld
- Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Peter G Passias
- Duke Spine Division, Departments of Neurological and Orthopaedic Surgery, Duke School of Medicine, Durham, NC, USA.
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Cheers GM, Weimer LP, Neuerburg C, Arnholdt J, Gilbert F, Thorwächter C, Holzapfel BM, Mayer-Wagner S, Laubach M. Advances in implants and bone graft types for lumbar spinal fusion surgery. Biomater Sci 2024; 12:4875-4902. [PMID: 39190323 DOI: 10.1039/d4bm00848k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/28/2024]
Abstract
The increasing prevalence of spinal disorders worldwide necessitates advanced treatments, particularly interbody fusion for severe cases that are unresponsive to non-surgical interventions. This procedure, especially 360° lumbar interbody fusion, employs an interbody cage, pedicle screw-and-rod instrumentation, and autologous bone graft (ABG) to enhance spinal stability and promote fusion. Despite significant advancements, a persistent 10% incidence of non-union continues to result in compromised patient outcomes and escalated healthcare costs. Innovations in lumbar stabilisation seek to mimic the properties of natural bone, with evolving implant materials like titanium (Ti) and polyetheretherketone (PEEK) and their composites offering new prospects. Additionally, biomimetic cages featuring precisely engineered porosities and interconnectivity have gained traction, as they enhance osteogenic differentiation, support osteogenesis, and alleviate stress-shielding. However, the limitations of ABG, such as harvesting morbidities and limited fusion capacity, have spurred the exploration of sophisticated solutions involving advanced bone graft substitutes. Currently, demineralised bone matrix and ceramics are in clinical use, forming the basis for future investigations into novel bone graft substitutes. Bioglass, a promising newcomer, is under investigation despite its observed rapid absorption and the potential for foreign body reactions in preclinical studies. Its clinical applicability remains under scrutiny, with ongoing research addressing challenges related to burst release and appropriate dosing. Conversely, the well-documented favourable osteogenic potential of growth factors remains encouraging, with current efforts focused on modulating their release dynamics to minimise complications. In this evidence-based narrative review, we provide a comprehensive overview of the evolving landscape of non-degradable spinal implants and bone graft substitutes, emphasising their applications in lumbar spinal fusion surgery. We highlight the necessity for continued research to improve clinical outcomes and enhance patient well-being.
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Affiliation(s)
- Giles Michael Cheers
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Lucas Philipp Weimer
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Carl Neuerburg
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Jörg Arnholdt
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Fabian Gilbert
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Christoph Thorwächter
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Boris Michael Holzapfel
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Susanne Mayer-Wagner
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Markus Laubach
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
- Australian Research Council (ARC) Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D Innovation), Queensland University of Technology, Brisbane, QLD 4000, Australia
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Lechtholz-Zey EA, Ayad M, Gettleman BS, Mills ES, Shelby H, Ton AT, Shah I, Wang JC, Hah RJ, Alluri RK. Systematic Review and Meta-Analysis of the Effect of Osteoporosis on Reoperation Rates and Complications after Surgical Management of Lumbar Degenerative Disease. J Bone Metab 2024; 31:114-131. [PMID: 38886969 PMCID: PMC11184153 DOI: 10.11005/jbm.2024.31.2.114] [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] [Received: 01/10/2024] [Revised: 04/21/2024] [Accepted: 04/22/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND There is considerable heterogeneity in findings and a lack of consensus regarding the interplay between osteoporosis and outcomes in patients with lumbar degenerative spine disease. Therefore, the purpose of this systematic review and meta-analysis was to gather and analyze existing data on the effect of osteoporosis on radiographic, surgical, and clinical outcomes following surgery for lumbar degenerative spinal disease. METHODS A systematic review was performed to determine the effect of osteoporosis on the incidence of adverse outcomes after surgical intervention for lumbar degenerative spinal diseases. The approach focused on the radiographic outcomes, reoperation rates, and other medical and surgical complications. Subsequently, a meta-analysis was performed on the eligible studies. RESULTS The results of the meta-analysis suggested that osteoporotic patients experienced increased rates of adjacent segment disease (ASD; p=0.015) and cage subsidence (p=0.001) while demonstrating lower reoperation rates than non-osteoporotic patients (7.4% vs. 13.1%; p=0.038). The systematic review also indicated that the length of stay, overall costs, rates of screw loosening, and rates of wound and other medical complications may increase in patients with a lower bone mineral density. Fusion rates, as well as patient-reported and clinical outcomes, did not differ significantly between osteoporotic and non-osteoporotic patients. CONCLUSIONS Osteoporosis was associated with an increased risk of ASD, cage migration, and possibly postoperative screw loosening, as well as longer hospital stays, incurring higher costs and an increased likelihood of postoperative complications. However, a link was not established between osteoporosis and poor clinical outcomes.
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Affiliation(s)
- Elizabeth A. Lechtholz-Zey
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA,
USA
| | - Mina Ayad
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA,
USA
| | - Brandon S. Gettleman
- Department of Orthopaedic Surgery, University of South Carolina School of Medicine, Columbia, SC,
USA
| | - Emily S. Mills
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA,
USA
| | - Hannah Shelby
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA,
USA
| | - Andy T. Ton
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA,
USA
| | - Ishan Shah
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA,
USA
| | - Jeffrey C. Wang
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA,
USA
| | - Raymond J. Hah
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA,
USA
| | - Ram K. Alluri
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA,
USA
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Salamanna F, Tedesco G, Sartori M, Griffoni C, Spinnato P, Romeo P, Ghermandi R, Fini M, Giavaresi G, Gasbarrini A, Barbanti Brodano G. Safety and efficacy of autologous bone marrow clot as a multifunctional bioscaffold for instrumental posterior lumbar fusion: a 1-year follow-up pilot study. Front Endocrinol (Lausanne) 2024; 14:1245344. [PMID: 38260131 PMCID: PMC10801235 DOI: 10.3389/fendo.2023.1245344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 12/12/2023] [Indexed: 01/24/2024] Open
Abstract
Background Bone marrow aspirate (BMA), when combined with graft substitutes, has long been introduced as a promising alternative to iliac crest bone graft in spinal fusion. However, the use of BMA is limited by the absence of a standardized procedure, a structural texture, and the potential for diffusion away from the implant site. Recently, the potential use of a new formulation of BMA, named BMA clot, has been preclinically described. In this report, we present the results of a prospective pilot clinical study aimed at evaluating the safety and efficacy of autologous vertebral BMA (vBMA) clot as a three-dimensional and multifunctional bioscaffold in instrumented posterior lumbar fusion. Methods Ten consecutive patients with an indication of multilevel (≤5) posterior spinal fusion due to lumbar spine degenerative diseases were included in the study and treated with vBMA. Clinical outcomes were assessed using the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and EuroQoL-5L (EQ-5L) preoperatively and at 3 months and 12 months after spinal fusion. Bone fusion quality was evaluated at the 12-month follow-up using the Brantigan classification on radiography (XR) imaging. Bone density was measured on computed tomography (CT) scans at 6 and 12 months of follow-up visits at the intervertebral arches and intervertebral joint areas and expressed in Hounsfield unit (HU). Results The results indicate a successful posterolateral fusion rate of approximately 100% (considering levels with C, D, and E grades according to the Brantigan classification) at the 12-month follow-up, along with an increase in bone density from 6 to 12 months of follow-up. An improvement in the quality of life and health status following surgery, as assessed by clinical scores (ODI, VAS, and EQ-5L), was also observed as early as 3 months postsurgery. No adverse events related to the vBMA clot were reported. Conclusion This prospective pilot study demonstrates the effectiveness and safety profile of vBMA clot as an advanced bioscaffold capable of achieving posterior lumbar fusion in the treatment of degenerative spine diseases. This lays the groundwork for a larger randomized clinical study.
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Affiliation(s)
- Francesca Salamanna
- Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Giuseppe Tedesco
- Spine Surgery Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Maria Sartori
- Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | | | - Paolo Spinnato
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Paolo Romeo
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | | | - Milena Fini
- Scientific Direction, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Gianluca Giavaresi
- Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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Weiss MB, Konopka JA, Azam MT, Ubillus HA, Mercer NP, Kennedy JG. Calcaneal reconstruction using a femoral head allograft and biologic adjuncts: A case report. SAGE Open Med Case Rep 2022; 10:2050313X221129782. [PMID: 36569037 PMCID: PMC9772964 DOI: 10.1177/2050313x221129782] [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: 07/11/2022] [Accepted: 09/13/2022] [Indexed: 12/27/2022] Open
Abstract
We present a case of calcaneal reconstruction after both an improvised explosive device injury and subsequent salvage procedures left the patient with a large calcaneal defect and damaged hindfoot soft tissue. A subtalar arthrodesis was performed with a femoral head allograft, where it was fused to the remaining calcaneus and superiorly through the talus, to successfully reconstruct this defect. Demineralized bone matrix, bone morphogenetic protein, and concentrated bone marrow aspirate were also added as adjuncts to promote bone remodeling. At final follow-up, the patient denied pain, was fully weight-bearing, and had resumed an active lifestyle. Level of Evidence: Level V, Case Report.
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Affiliation(s)
| | | | | | | | | | - John G Kennedy
- John G Kennedy, Department of Orthopedic Surgery, New York University Langone Health, 171 Delancey Street, New York, NY 10002, USA.
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Loenen ACY, Peters MJM, Wierts R, Bevers RTJ, van Rhijn LW, Arts JJ, Willems PC. Local bone metabolism during the consolidation process of spinal interbody fusion. J Bone Miner Metab 2022; 40:220-228. [PMID: 34755216 DOI: 10.1007/s00774-021-01281-8] [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: 07/26/2021] [Accepted: 10/14/2021] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Although computed tomography (CT) can identify the presence of eventual bony bridges following lumbar interbody fusion (LIF) surgery, it does not provide information on the ongoing formation process of new bony structures. 18F sodium fluoride (18F-NaF) positron emission tomography (PET) could be used as complementary modality to add information on the bone metabolism at the fusion site. However, it remains unknown how bone metabolism in the operated segment changes early after surgery in uncompromised situations. This study aimed to quantify the changes in local bone metabolism during consolidation of LIF. MATERIALS AND METHODS Six skeletally mature sheep underwent LIF surgery. 18F-NaF PET/CT scanning was performed 6 and 12 weeks postoperatively to quantify the bone volume and metabolism in the operated segment. Bone metabolism was expressed as a function of bone volume. RESULTS Early in the fusion process, bone metabolism was increased at the endplates of the operated vertebrae. In a next phase, bone metabolism increased in the center of the interbody region, peaked, and declined to an equilibrium state. During the entire postoperative time period of 12 weeks, bone metabolism in the interbody region was higher than that of a reference site in the spinal column. CONCLUSION Following LIF surgery, there is a rapid increase in bone metabolism at the vertebral endplates that develops towards the center of the interbody region. Knowing the local bone metabolism during uncompromised consolidation of spinal interbody fusion might enable identification of impaired bone formation early after LIF surgery using 18F-NaF PET/CT scanning.
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Affiliation(s)
- Arjan C Y Loenen
- Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, CAPHRI, Maastricht University Medical Center, Maastricht, The Netherlands
- Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
| | - Marloes J M Peters
- Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, CAPHRI, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Roel Wierts
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Raymond T J Bevers
- Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, CAPHRI, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Lodewijk W van Rhijn
- Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, CAPHRI, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Jacobus J Arts
- Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, CAPHRI, Maastricht University Medical Center, Maastricht, The Netherlands
- Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
| | - Paul C Willems
- Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, CAPHRI, Maastricht University Medical Center, Maastricht, The Netherlands.
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Wickramasinghe ML, Dias GJ, Premadasa KMGP. A novel classification of bone graft materials. J Biomed Mater Res B Appl Biomater 2022; 110:1724-1749. [PMID: 35156317 DOI: 10.1002/jbm.b.35029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 01/20/2022] [Accepted: 01/21/2022] [Indexed: 12/19/2022]
Affiliation(s)
- Maduni L. Wickramasinghe
- Department of Biomedical Engineering General Sir John Kotelawala Defense University Ratmalana Sri Lanka
| | - George J. Dias
- Department of Anatomy, School of Medical Sciences University of Otago Dunedin New Zealand
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Noh T, Zakaria H, Massie L, Ogasawara CT, Lee GA, Chedid M. Bone Marrow Aspirate in Spine Surgery: Case Series and Review of the Literature. Cureus 2021; 13:e20309. [PMID: 35028210 PMCID: PMC8748018 DOI: 10.7759/cureus.20309] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2021] [Indexed: 12/02/2022] Open
Abstract
Background With the modernization of biotechnology, there has been a concerted effort to create novel biomaterials to promote arthrodesis for spine surgery. The novel use of the stem cells from bone marrow aspirate (BMA) to augment spine surgery is a burgeoning field because these cells are considered to be both osteoinductive and osteogenic. We sought to review the evidence behind the use of BMAs in spinal fusions and report the results of our own case series. Methods PubMed and EMBASE databases were searched for studies that investigated the use of stem cells for spine surgery. For our own case series, the medical records of 150 consecutive patients who underwent a lumbar spinal fusion with BMA were retrospectively reviewed for adverse events (AEs) for up to two years after surgery. Results In our case series, there were no AEs identified in 49% of our patients. Of the identified AEs, 61% were unrelated to the use of BMA (e.g., UTI and heart failure), with the remaining 39% likely unrelated to its use (e.g., back pain and anemia). There was a 92.8% arthrodesis rate with the use of BMA. Conclusions We reviewed the rationale, basic science, and clinical science for BMA usage in spine surgery and concluded that BMA is safe for use in spine surgery and is associated with a high rate of arthrodesis.
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Affiliation(s)
- Thomas Noh
- Division of Neurological Surgery, University of Hawaii John A. Burns School of Medicine, Honolulu, USA
| | - Hesham Zakaria
- Department of Neurological Surgery, Henry Ford Health System, Detroit, USA
| | - Lara Massie
- Department of Neurological Surgery, Henry Ford Health System, Detroit, USA
| | - Christian T Ogasawara
- Division of Neurological Surgery, University of Hawaii John A. Burns School of Medicine, Honolulu, USA
| | - Gunnar A Lee
- Division of Neurological Surgery, University of Hawaii John A. Burns School of Medicine, Honolulu, USA
| | - Mokbel Chedid
- Department of Neurological Surgery, Henry Ford Health System, Detroit, USA
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Feddahi N, Herten M, Tassemeier T, Rekasi H, Hackel A, Haversath M, Jäger M. Does Needle Design Affect the Regenerative Potential of Bone Marrow Aspirate? An In Vitro Study. Life (Basel) 2021; 11:748. [PMID: 34440491 PMCID: PMC8401947 DOI: 10.3390/life11080748] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 07/19/2021] [Accepted: 07/20/2021] [Indexed: 11/17/2022] Open
Abstract
While autologous bone is still the gold standard for treatment of bone defects, its availability is limited. Sufficient numbers of mesenchymal stroma cells (MSC) may be an alternative. Small volumes of bone marrow aspirate (BMA) were harvested with two different needle systems comparing the yield and regenerative potency of the MSCs. BMA (10 mL) was aspirated from the posterior iliac crest of 12 patients with degenerative spinal disc disease using both needle systems in each patient: the Jamshidi needle (JAM) and on the contralateral side the Marrow Cellution® Needle (AMC). Number of mononuclear cells (MNCs) and regeneration capacity (colony-forming unit/CFU) were determined. MSCs were characterized for surface markers and their differentiation into trilineages. There was no significant difference between the two harvesting needles regarding the quantity of MNCs in BMA: 5.2 ± 1.8 × 109 MNC/mL for AMC vs. 4.8 ± 2.5 × 109 MNC/mL for JAM, p = 0.182. The quantity of CFUs per ml BMA was similar for both groups: 3717 ± 5556 for AMC and 4305 ± 5507 for JAM (p = 0.695). The potency of MSCs expressed as colony-forming potential per 106 MNC resulted in 0.98 ± 1.51 for AMC and 1.00 ± 0.96 for JAM (p = 0.666). Regardless of the needle design, 10 mL bone marrow aspirate contains a sufficient number of about 40,000 MSCs that can be used to enhance bone healing.
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Affiliation(s)
- Nadia Feddahi
- Department of Orthopedic and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen, Germany; (H.R.); (M.H.)
| | - Monika Herten
- Clinic of Trauma, Hand and Reconstructive Surgery, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen, Germany;
| | - Tjark Tassemeier
- Department of Orthopedic, Gelenkzentrum Bergisch Land, Freiheitstraße 203, D-42853 Remscheid, Germany;
| | - Heike Rekasi
- Department of Orthopedic and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen, Germany; (H.R.); (M.H.)
| | - Alexander Hackel
- Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen, Germany;
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany
| | - Marcel Haversath
- Department of Orthopedic and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen, Germany; (H.R.); (M.H.)
- Department of Orthopedic, St. Vinzenz Krankenhaus Düsseldorf, Schloßstraße 85, D-40477 Düsseldorf, Germany
| | - Marcus Jäger
- Department of Trauma, Reconstruction and Orthopedic Surgery, St. Marien Hospital, Mülheim an der Ruhr, Kaiserstraße 50, D-45468 Mülheim an der Ruhr, Germany;
- Orthopedics and Trauma Surgery, University of Duisburg Essen, D-45147 Essen, Germany
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Lumbar interbody fusion: recent advances in surgical techniques and bone healing strategies. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2020; 30:22-33. [DOI: 10.1007/s00586-020-06596-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 08/26/2020] [Accepted: 09/05/2020] [Indexed: 12/31/2022]
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Eder C, Schmidt-Bleek K, Geissler S, Sass FA, Maleitzke T, Pumberger M, Perka C, Duda GN, Winkler T. Mesenchymal stromal cell and bone marrow concentrate therapies for musculoskeletal indications: a concise review of current literature. Mol Biol Rep 2020; 47:4789-4814. [PMID: 32451926 PMCID: PMC7295724 DOI: 10.1007/s11033-020-05428-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 04/03/2020] [Indexed: 12/17/2022]
Abstract
The interest on applying mesenchymal stromal cells (MSCs) in orthopedic disorders has risen tremendously in the last years due to scientific successes in preclinical in vitro and animal model studies. In a wide range of diseases and injuries of the musculoskeletal system, MSCs are currently under evaluation, but so far have found access to clinical use only in few cases. The current assignment is to translate the acquired knowledge into clinical practice. Therefore, this review aims at presenting a synopsis of the up-to-date status of the use of MSCs and MSC related cell products in musculoskeletal indications. Clinical studies were included, whereas preclinical and animal study data not have been considered. Most studies published so far investigate the final outcome applying bone marrow derived MSCs. In fewer trials the use of adipose tissue derived MSCs and allogenic MSCs was investigated in different applications. Although the reported results are equivocal in the current literature, the vast majority of the studies shows a benefit of MSC based therapies depending on the cell sources and the indication in clinical use. In summary, the clinical use of MSCs in patients in orthopedic indications has been found to be safe. Standardized protocols and clear definitions of the mechanisms of action and the mode and timing of application as well as further coordinated research efforts will be necessary for finally adding MSC based therapies in standard operating procedures and guidelines for the clinicians treating orthopedic disorders.
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Affiliation(s)
- Christian Eder
- Center for Musculoskeletal Surgery, Charité - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany
| | - Katharina Schmidt-Bleek
- Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health Center for Regenerative Therapies, Charité – Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Sven Geissler
- Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health Center for Regenerative Therapies, Charité – Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - F. Andrea Sass
- Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health Center for Regenerative Therapies, Charité – Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Tazio Maleitzke
- Center for Musculoskeletal Surgery, Charité - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany
| | - Matthias Pumberger
- Center for Musculoskeletal Surgery, Charité - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany
| | - Carsten Perka
- Center for Musculoskeletal Surgery, Charité - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany
- Berlin-Brandenburg School for Regenerative Therapies, Charité – Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Georg N. Duda
- Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health Center for Regenerative Therapies, Charité – Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin-Brandenburg School for Regenerative Therapies, Charité – Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Tobias Winkler
- Center for Musculoskeletal Surgery, Charité - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany
- Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health Center for Regenerative Therapies, Charité – Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
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Cho PG, Ji GY, Ha Y, Lee HY, Shin DA. Effect of the type of electrical stimulation on spinal fusion in a rat posterolateral spinal fusion model. Spine J 2019; 19:1106-1120. [PMID: 30584910 DOI: 10.1016/j.spinee.2018.12.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 12/19/2018] [Accepted: 12/19/2018] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Posterolateral fusion (PLF) with autogenous iliac bone graft is one of the most common surgical procedures for lumbar spinal disease. However, its limited success demands new biologically competent graft enhancers or substitutes. Although the use of direct current (DC) electrical stimulation has been shown to increase rate of successful spinal fusions, little is known about the effect of the type of current in DC stimulation. PURPOSE To evaluate the effects of various DC stimulators on the strength and success rate of posterolateral fusion facilitated by using a nitinol mesh container, in rats. STUDY DESIGN This was an experimental animal study. METHODS A conductive, tubular nitinol mesh container was used to carry small pieces of bone grafts. The nitinol mesh container received electrical stimulation via a lead that connected the container to different types of DC stimulators. Sixty male Sprague-Dawley rats were divided into three groups (N=20 in each): a control group that underwent PLF with a nitinol container filled with autograft, a constant DC group that received a nitinol container and constant DC (100 μA), and a pulsed DC group that received a nitinol container and pulsed DC (100 μA, 100 Hz, 200 μs). The rats underwent PLF between L4 and L5, and transverse processes were grafted with bilateral iliac grafts. A stimulator was implanted subcutaneously. The rats were sacrificed 8 weeks postsurgery, and lumbar spines were removed. Spinal fusion was evaluated by microcomputed tomography, manual testing, biomechanical testing, histologic examination, and molecular analysis. RESULTS All animals in the DC stimulation groups displayed solid fusion, whereas only 70% of control animals showed solid fusion. Radiographic images, biomechanical testing, histologic examination, and molecular analysis revealed improved fusion in the order control group<constant DC group<pulsed DC group. The volume of new bone mass was significantly higher in the pulsed DC group (p<.05). Fusion was more solid in the pulsed DC group than in control group (p<.05). The pulsed DC group displayed the lowest inflammatory responses. CONCLUSIONS Pulsed DC electrical stimulation is efficacious in improving both strength and fusion rate in a rat spinal fusion model. In addition, tubular nitinol mesh, made of conductive suture, appears useful for holding small pieces of bone grafts and maintaining a good environment for bone fusion. CLINICAL RELEVANCE Pulsed DC electrical stimulation may be potentially useful to increase the fusion rate after spinal fusion in humans. Future research is required to evaluate the safety and efficacy of tubular nitinol mesh and pulsed DC electrical stimulation in humans.
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Affiliation(s)
- Pyung Goo Cho
- Department of Neurosurgery, Bundang Jesaeng Hospital, Seongnam si, Republic of Korea
| | - Gyu Yeol Ji
- Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yoon Ha
- Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hye Yeong Lee
- Spine and Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dong Ah Shin
- Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Greene AC, Hsu WK. Orthobiologics in minimally invasive lumbar fusion. JOURNAL OF SPINE SURGERY 2019; 5:S11-S18. [PMID: 31380488 DOI: 10.21037/jss.2019.04.15] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Minimally invasive (MI) spine surgery continues to gain popularity with patients and surgeons for its potential to decrease operative time and avoid complications commonly associated with open surgery. In the face of a changing surgical landscape, selecting the appropriate implant material to be used in MI lumbar fusion procedures will remain critically important. Various orthobiologic materials are available for use, including autologous and allogeneic bone graft, bone marrow aspirate (BMA), demineralized bone matrix (DBM), ceramics, and growth factors. The purpose of this review is to summarize the use and efficacy of currently available products, as well as highlight the development of novel therapeutic options.
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Affiliation(s)
- Allison C Greene
- Northwestern University Department of Orthopaedic Surgery, Chicago, IL, USA.,Simpson Querrey Institute, Northwestern University, Chicago, IL, USA
| | - Wellington K Hsu
- Northwestern University Department of Orthopaedic Surgery, Chicago, IL, USA.,Simpson Querrey Institute, Northwestern University, Chicago, IL, USA
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15
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Ding M, Koroma KE, Sorensen JR, Sandri M, Tampieri A, Jespersen SM, Overgaard S. Collagen-hydroxyapatite composite substitute and bone marrow nuclear cells on posterolateral spine fusion in sheep. J Biomater Appl 2019; 34:365-374. [PMID: 31109260 DOI: 10.1177/0885328219851315] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Ming Ding
- 1 Orthopaedic Research Unit, Department of Orthopaedic Surgery & Traumatology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Kariatta Esther Koroma
- 1 Orthopaedic Research Unit, Department of Orthopaedic Surgery & Traumatology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jesper Roed Sorensen
- 1 Orthopaedic Research Unit, Department of Orthopaedic Surgery & Traumatology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Monica Sandri
- 2 Institute of Science and Technology for Ceramics, National Research Council (ISTEC-CNR), Faenza, Italy
| | - Anna Tampieri
- 2 Institute of Science and Technology for Ceramics, National Research Council (ISTEC-CNR), Faenza, Italy
| | - Stig M Jespersen
- 1 Orthopaedic Research Unit, Department of Orthopaedic Surgery & Traumatology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Søren Overgaard
- 1 Orthopaedic Research Unit, Department of Orthopaedic Surgery & Traumatology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Salamanna F, Giavaresi G, Contartese D, Bigi A, Boanini E, Parrilli A, Lolli R, Gasbarrini A, Barbanti Brodano G, Fini M. Effect of strontium substituted ß-TCP associated to mesenchymal stem cells from bone marrow and adipose tissue on spinal fusion in healthy and ovariectomized rat. J Cell Physiol 2019; 234:20046-20056. [PMID: 30950062 DOI: 10.1002/jcp.28601] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 03/11/2019] [Accepted: 03/19/2019] [Indexed: 01/05/2023]
Abstract
Despite alternatives to autogenous bone graft for spinal fusion have been investigated, it has been shown that osteoconductive materials alone do not give a rate of fusion comparable with autogenous bone. This study analyzed a strontium substituted ß-tricalcium phosphate (Sr-ßTCP) associated with syngeneic, unexpanded, and undifferentiated mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ADSC) as a new tissue engineering approach for spinal fusion procedures. A posterolateral fusion was performed in 15 ovariectomized (OVX) and 15 sham-operated (SHAM) Inbred rats. Both SHAM and OVX animals were divided into three groups: Sr-ßTCP, Sr-ßTCP + BMCSs, and Sr-ßTCP + ADSCs. Animals were euthanized 8 weeks after surgery and the spines evaluated by manual palpation, micro-CT, and histology. For both SHAM and OVX animals, the fusion tissue in the Sr-ßTCP + BMSCs group was more solid. This effect was significantly higher in OVX animals by comparing the Sr-ßTCP + BMCSs group with Sr-ßTCP + ADSCs. Radiographical score, based on micro-CT 2D image, highlighted that the Sr-ßTCP + BMCSs group presented a similar fusion to Sr-ßTCP and higher than Sr-ßTCP + ADSCs in both SHAM and OVX animals. Micro-CT 3D parameters did not show significant differences among groups. Histological score showed significantly higher fusion in Sr-ßTCP + BMSCs group than Sr-ßTCP and Sr-ßTCP + ADSCs, for both SHAM and OVX animals. In conclusion, our results suggest that addition of BMSCs to a Sr-ßTCP improve bone formation and fusion, both in osteoporotic and nonosteoporotic animal, whereas spinal fusion is not enhanced in rats treated with Sr-ßTCP + ADSCs. Thus, for conducting cells therapy in spinal surgery BMSCs still seems to be a better choice compared with ADSCs.
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Affiliation(s)
- Francesca Salamanna
- Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Gianluca Giavaresi
- Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Deyanira Contartese
- Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Adriana Bigi
- Department of Chemistry "G.Ciamician", University of Bologna, Bologna, Italy
| | - Elisa Boanini
- Department of Chemistry "G.Ciamician", University of Bologna, Bologna, Italy
| | - Annapaola Parrilli
- Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Roberta Lolli
- Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Alessandro Gasbarrini
- Department of Oncological and Degenerative Spine Surgery, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Giovanni Barbanti Brodano
- Department of Oncological and Degenerative Spine Surgery, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Milena Fini
- Laboratory of Biomechanics and Technological Innovation, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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18
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Multiple integrin ligands provide a highly adhesive and osteoinductive surface that improves selective cell retention technology. Acta Biomater 2019; 85:106-116. [PMID: 30557698 DOI: 10.1016/j.actbio.2018.12.018] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 12/11/2018] [Accepted: 12/13/2018] [Indexed: 01/01/2023]
Abstract
Among various bone tissue engineering strategies, selective cell retention (SCR) technology has been used as a practical clinical method for bone graft manufacturing in real time. The more mesenchymal stem cells (MSCs) are retained, the better the osteoinductive microenvironment provided by the scaffold, which in turn promotes the osteogenesis of the SCR-fabricated bone grafts. Integrin receptors are crucial to cell-matrix adhesion and signal transduction. We designed a collagen-binding domain (CBD)-containing IKVAV-cRGD peptide (CBD-IKVAV-cRGD peptide) to complement the collagen-based demineralized bone matrix (DBM) with a functionalized surface containing multiple integrin ligands, which correspond to the highly expressed integrin subtypes on MSCs. This DBM/CBD-IKVAV-cRGD composite exhibited superior in vitro adhesion capacity to cultured MSCs, as determined by oscillatory cell adhesion assay, centrifugal cell adhesion assay and mimetic SCR. Moreover, it promoted the retention of MSC-like CD271+ cells and MSC-like CD90+/CD105+ cells in the clinical SCR method. Furthermore, the DBM/CBD-IKVAV-cRGD composite induced robust MSC osteogenesis, coupled with the activation of the downstream FAK-ERK1/2 signaling pathway of integrins. The SCR-prepared DBM/CBD-IKVAV-cRGD composite displayed superior in vivo osteogenesis, indicating that it may be potentially utilized as a biomaterial in SCR-mediated bone transplantation. STATEMENT OF SIGNIFICANCE: Selective cell retention technology (SCR) has been utilized in clinical settings to manufacture bioactive bone grafts. Specifically, demineralized bone matrix (DBM) is a widely-used SCR clinical biomaterial but it displays poor adhesion performance and osteoinduction. Improvements of the DBM that promote cell adhesion and osteoinduction will benefit SCR-prepared implants. In this work, we developed a novel peptide that complements the DBM with a functionalized surface of multiple integrin ligands, which are corresponding to integrin subtypes available on human bone marrow-derived mesenchymal stem cells (MSCs). Our results indicate this novel functionalized bioscaffold greatly increases SCR-mediated MSC adhesion and in vivo osteogenesis. Overall, this novel material has promising SCR applications and may likely provide highly bioactive bone implants in clinical settings.
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Abstract
STUDY DESIGN Systematic review. OBJECTIVE The aim of this study was to investigate, quantify, compare, and compile the various mesenchymal stem cell (MSC) tissue sources within human spinal tissues to act as a compendium for clinical and research application. SUMMARY OF BACKGROUND DATA Recent years have seen a dramatic increase in academic and clinical understanding of human MSCs. Previously limited to cells isolated from bone marrow, the past decade has illicited the characterization and isolation of human MSCs from adipose, bone marrow, synovium, muscle, periosteum, peripheral blood, umbilical cord, placenta, and numerous other tissues. As researchers explore practical applications of cells in these tissues, the absolute levels of MSCs in specific spinal tissue will be critical to guide future research. METHODS The PubMED, MEDLINE, EMBASE, and Cochrane databases were searched for articles relating to the harvest, characterization, isolation, and quantification of human MSCs from spinal tissues. Selected articles were examined for relevant data, categorized according to type of spinal tissue, and when possible, standardized to facilitate comparisons between sites. RESULTS Human MSC levels varied widely between spinal tissues. Yields for intervertebral disc demonstrated roughly 5% of viable cells to be positive for MSC surface markers. Cartilage endplate cells yielded 18,500 to 61,875 cells/0.8 mm thick sample of cartilage end plate. Ligamentum flavum yielded 250,000 to 500,000 cells/g of tissue. Annulus fibrosus fluorescence activated cell sorting treatment found 29% of cells positive for MSC marker Stro-1. Nucleus pulposus yielded mean tissue samples of 40,584 to 234,137 MSCs per gram of tissue. CONCLUSION Numerous tissues within and surrounding the spine represent a consistent and reliable source for the harvest and isolation of human MSCs. Among the tissues of the spine, the annulus fibrosus and ligamentum flavum each offer considerable levels of MSCs, and may prove comparable to that of bone marrow. LEVEL OF EVIDENCE 5.
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20
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Spinal Biologics in Minimally Invasive Lumbar Surgery. Minim Invasive Surg 2018; 2018:5230350. [PMID: 29850240 PMCID: PMC5907390 DOI: 10.1155/2018/5230350] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Accepted: 02/25/2018] [Indexed: 12/28/2022] Open
Abstract
As the use of minimally invasive spine (MIS) fusion approaches continues to grow, increased scrutiny is being placed on its outcomes and efficacies against traditional open fusion surgeries. While there are many factors that contribute to the success of achieving spinal arthrodesis, selecting the optimal fusion biologic remains a top priority. With an ever-expanding market of bone graft substitutes, it is important to evaluate each of their use as it pertains to MIS techniques. This review will summarize the important characteristics and properties of various spinal biologics used in minimally invasive lumbar surgeries and compare their fusion rates via a systematic review of published literature.
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Piuzzi NS, Hussain ZB, Chahla J, Cinque ME, Moatshe G, Mantripragada VP, Muschler GF, LaPrade RF. Variability in the Preparation, Reporting, and Use of Bone Marrow Aspirate Concentrate in Musculoskeletal Disorders: A Systematic Review of the Clinical Orthopaedic Literature. J Bone Joint Surg Am 2018; 100:517-525. [PMID: 29557869 DOI: 10.2106/jbjs.17.00451] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Interest in the therapeutic potential of bone marrow aspirate concentrate (BMAC) has grown exponentially. However, comparisons among studies and their processing methods are challenging because of inconsistent reporting of protocols, as well as poor characterization of the composition of the initial bone marrow aspirate and of the final products delivered. The purpose of this study was to perform a systematic review of the literature to evaluate the level of reporting related to the protocols used for BMAC preparation and the composition of BMAC utilized in the treatment of musculoskeletal diseases in published clinical studies. METHODS A systematic review of the literature was performed by searching PubMed, MEDLINE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials from 1980 to 2016. Inclusion criteria were human clinical trials, English language, and manuscripts that reported on the use of BMAC in musculoskeletal conditions. RESULTS After a comprehensive review of the 986 identified articles, 46 articles met the inclusion criteria for analysis. No study provided comprehensive reporting that included a clear description of the preparation protocol that could be used by subsequent investigators to repeat the method. Only 14 (30%) of the studies provided quantitative metrics of the composition of the BMAC final product. CONCLUSIONS The reporting of BMAC preparation protocols in clinical studies was highly inconsistent and studies did not provide sufficient information to allow the protocol to be reproduced. Moreover, comparison of the efficacy and yield of BMAC products is precluded by deficiencies in the reporting of preparation methods and composition. Future studies should contain standardized and stepwise descriptions of the BMAC preparation protocol, and the composition of the BMAC delivered, to permit validating and rationally optimizing the role of BMAC in musculoskeletal care.
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Affiliation(s)
- Nicolas S Piuzzi
- Department of Orthopaedic Surgery and Bioengineering, Cleveland Clinic, Cleveland, Ohio.,Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Jorge Chahla
- Steadman Philippon Research Institute, Vail, Colorado
| | - Mark E Cinque
- Steadman Philippon Research Institute, Vail, Colorado
| | - Gilbert Moatshe
- Steadman Philippon Research Institute, Vail, Colorado.,Oslo University Hospital, University of Oslo, Oslo, Norway.,OSTRC, The Norwegian School of Sports Sciences, Oslo, Norway
| | | | - George F Muschler
- Department of Orthopaedic Surgery and Bioengineering, Cleveland Clinic, Cleveland, Ohio
| | - Robert F LaPrade
- Steadman Philippon Research Institute, Vail, Colorado.,The Steadman Clinic, Vail, Colorado
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Zwolak P, Farei-Campagna J, Jentzsch T, von Rechenberg B, Werner CM. Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model. Arch Orthop Trauma Surg 2018; 138:13-18. [PMID: 29018937 DOI: 10.1007/s00402-017-2818-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Indexed: 11/29/2022]
Abstract
BACKGROUND Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model. METHODS A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery. RESULTS The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1-S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone. CONCLUSIONS A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our results justify further investigations to potentially use local application of zoledronic acid in future clinical studies.
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Affiliation(s)
- Pawel Zwolak
- Department of Trauma Surgery, University Hospital of Zurich, Rämistrasse 100, 8006, Zurich, Switzerland.
| | - Jan Farei-Campagna
- Department of Trauma Surgery, University Hospital of Zurich, Rämistrasse 100, 8006, Zurich, Switzerland
| | - Thorsten Jentzsch
- Department of Trauma Surgery, University Hospital of Zurich, Rämistrasse 100, 8006, Zurich, Switzerland
| | | | - Clément M Werner
- Department of Trauma Surgery, University Hospital of Zurich, Rämistrasse 100, 8006, Zurich, Switzerland
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Confalonieri D, Schwab A, Walles H, Ehlicke F. Advanced Therapy Medicinal Products: A Guide for Bone Marrow-derived MSC Application in Bone and Cartilage Tissue Engineering. TISSUE ENGINEERING PART B-REVIEWS 2017; 24:155-169. [PMID: 28990462 DOI: 10.1089/ten.teb.2017.0305] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Millions of people worldwide suffer from trauma- or age-related orthopedic diseases such as osteoarthritis, osteoporosis, or cancer. Tissue Engineering (TE) and Regenerative Medicine are multidisciplinary fields focusing on the development of artificial organs, biomimetic engineered tissues, and cells to restore or maintain tissue and organ function. While allogenic and future autologous transplantations are nowadays the gold standards for both cartilage and bone defect repair, they are both subject to important limitations such as availability of healthy tissue, donor site morbidity, and graft rejection. Tissue engineered bone and cartilage products represent a promising and alternative approach with the potential to overcome these limitations. Since the development of Advanced Therapy Medicinal Products (ATMPs) such as TE products requires the knowledge of diverse regulation and an extensive communication with the national/international authorities, the aim of this review is therefore to summarize the state of the art on the clinical applications of human bone marrow-derived stromal cells for cartilage and bone TE. In addition, this review provides an overview of the European legislation to facilitate the development and commercialization of new ATMPs.
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Affiliation(s)
- Davide Confalonieri
- 1 Department Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg , Wuerzburg, Germany
| | - Andrea Schwab
- 1 Department Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg , Wuerzburg, Germany
| | - Heike Walles
- 1 Department Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg , Wuerzburg, Germany .,2 Translational Center Wuerzburg "Regenerative Therapies in Oncology and Musculoskeletal Disease," Wuerzburg, Germany
| | - Franziska Ehlicke
- 1 Department Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg , Wuerzburg, Germany
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24
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Spalthoff S, Zimmerer R, Dittmann J, Kokemüller H, Tiede M, Flohr L, Korn P, Gellrich NC, Jehn P. Heterotopic bone formation in the musculus latissimus dorsi of sheep using β-tricalcium phosphate scaffolds: evaluation of different seeding techniques. Regen Biomater 2017; 5:77-84. [PMID: 29644089 PMCID: PMC5888254 DOI: 10.1093/rb/rbx029] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Revised: 09/27/2017] [Accepted: 09/28/2017] [Indexed: 12/21/2022] Open
Abstract
Osseous reconstruction of large bone defects remains a challenge in oral and maxillofacial surgery. In addition to autogenous bone grafts, which despite potential donor-site mobility still represent the gold standard in reconstructive surgery, many studies have investigated less invasive alternatives such as in vitro cultivation techniques. This study compared different types of seeding techniques on pure β-tricalcium phosphate scaffolds in terms of bone formation and ceramic resorption in vivo. Cylindrical scaffolds loaded with autologous cancellous bone, venous blood, bone marrow aspirate concentrate or extracorporeal in vitro cultivated bone marrow stromal cells were cultured in sheep on a perforator vessel of the musculus latissimus dorsi over a 6-month period. Histological and histomorphometric analyses revealed that scaffolds loaded with cancellous bone were superior at promoting heterotopic bone formation and ceramic degradation, with autogenous bone and bone marrow aspirate concentrate inducing in vivo formation of vital bone tissue. These results confirm that autologous bone constitutes the preferred source of osteoinductive and osteogenic material that can reliably induce heterotopic bone formation in vivo.
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Affiliation(s)
- Simon Spalthoff
- Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany and
- Correspondence address. Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany. Tel: +49-511-532-4879; Fax: +49-511-532-18598; E-mail:
| | - Rüdiger Zimmerer
- Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany and
| | - Jan Dittmann
- Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany and
| | - Horst Kokemüller
- Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany and
| | - Marco Tiede
- Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany
| | - Laura Flohr
- Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany and
| | - Philippe Korn
- Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany and
| | - Nils-Claudius Gellrich
- Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany and
| | - Philipp Jehn
- Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany and
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25
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Walmsley GG, Ransom RC, Zielins ER, Leavitt T, Flacco JS, Hu MS, Lee AS, Longaker MT, Wan DC. Stem Cells in Bone Regeneration. Stem Cell Rev Rep 2017; 12:524-529. [PMID: 27250635 DOI: 10.1007/s12015-016-9665-5] [Citation(s) in RCA: 107] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Bone has the capacity to regenerate and repair itself. However, this capacity may be impaired or lost depending on the size of the defect or the presence of certain disease states. In this review, we discuss the key principles underlying bone healing, efforts to characterize bone stem and progenitor cell populations, and the current status of translational and clinical studies in cell-based bone tissue engineering. Though barriers to clinical implementation still exist, the application of stem and progenitor cell populations to bone engineering strategies has the potential to profoundly impact regenerative medicine.
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Affiliation(s)
- Graham G Walmsley
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Drive Room GK106, Stanford, CA, 94305-5461, USA.,Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Hagey Building, 257 Campus Dr., Stanford, CA, 94305, USA
| | - Ryan C Ransom
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Drive Room GK106, Stanford, CA, 94305-5461, USA.,Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Hagey Building, 257 Campus Dr., Stanford, CA, 94305, USA
| | - Elizabeth R Zielins
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Drive Room GK106, Stanford, CA, 94305-5461, USA
| | - Tripp Leavitt
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Drive Room GK106, Stanford, CA, 94305-5461, USA
| | - John S Flacco
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Drive Room GK106, Stanford, CA, 94305-5461, USA
| | - Michael S Hu
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Drive Room GK106, Stanford, CA, 94305-5461, USA.,Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Hagey Building, 257 Campus Dr., Stanford, CA, 94305, USA.,Department of Surgery, John A. Burns School of Medicine, University of Hawai'i, Honolulu, Hawai'i, USA
| | - Andrew S Lee
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Hagey Building, 257 Campus Dr., Stanford, CA, 94305, USA
| | - Michael T Longaker
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Drive Room GK106, Stanford, CA, 94305-5461, USA.,Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Hagey Building, 257 Campus Dr., Stanford, CA, 94305, USA
| | - Derrick C Wan
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Drive Room GK106, Stanford, CA, 94305-5461, USA.
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26
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Choma TJ, Mroz TE, Goldstein CL, Arnold P, Shamji MF. Emerging Techniques in Degenerative Thoracolumbar Surgery. Neurosurgery 2017; 80:S55-S60. [PMID: 28350946 DOI: 10.1093/neuros/nyw079] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 11/21/2016] [Indexed: 11/15/2022] Open
Abstract
There continue to be incremental advances in thoracolumbar spine surgery techniques in attempts to achieve more predictable outcomes, minimize risk of complications, speed recovery, and minimize the costs of these interventions. This paper reviews recent literature with regard to emerging techniques of interest in the surgical treatment of lumbar spinal stenosis, fusion fixation and graft material, degenerative lumbar spondylolisthesis, and thoracolumbar deformity and sacroiliac joint degeneration. There continue to be advances in minimal access options in these areas, although robust outcome data are heterogeneous in its support. The evidence in support of sacroiliac fusion appears to be growing more robust in the properly selected patient.
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Affiliation(s)
- Theodore J Choma
- Department of Orthopaedic Surgery, University of Missouri, Columbia, Miss-ouri
| | - Thomas E Mroz
- Departments of Orthopaedic and Neurological Surgery, Cleveland Clinic, Cleveland, Ohio
| | | | - Paul Arnold
- Department of Neuro-surgery, University of Kansas, Kansas City, Kansas
| | - Mohammed F Shamji
- Department of Surgery, Uni-versity of Toronto, Toronto, Canada.,Divi-sion of Neurosurgery, Toronto Western Hospital, Toronto, Canada
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27
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Quantitative Assessment of Optimal Bone Marrow Site for the Isolation of Porcine Mesenchymal Stem Cells. Stem Cells Int 2017; 2017:1836960. [PMID: 28539939 PMCID: PMC5429955 DOI: 10.1155/2017/1836960] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Accepted: 03/28/2017] [Indexed: 12/13/2022] Open
Abstract
Background. One of the most plentiful sources for MSCs is the bone marrow; however, it is unknown whether MSC yield differs among different bone marrow sites. In this study, we quantified cellular yield and evaluated resident MSC population from five bone marrow sites in the porcine model. In addition, we assessed the feasibility of a commercially available platelet concentrator (Magellan® MAR01™ Arteriocyte Medical Systems, Hopkinton, MA) as a bedside stem cell concentration device. Methods. Analyses of bone marrow aspirate (BMA) and concentrated bone marrow aspirate (cBMA) included bone marrow volume, platelet and nucleated cell yield, colony-forming unit fibroblast (CFU-F) number, flow cytometry, and assessment of differentiation potential. Results. Following processing, the concentration of platelets and nucleated cells significantly increased but was not significantly different between sites. The iliac crest had significantly less bone marrow volume; however, it yielded significantly more CFUs compared to the other bone marrow sites. Culture-expanded cells from all tested sites expressed high levels of MSC surface markers and demonstrated adipogenic and osteogenic differentiation potential. Conclusions. All anatomical bone marrow sites contained MSCs, but the iliac crest was the most abundant source of MSCs. Additionally, the Magellan can function effectively as a bedside stem cell concentrator.
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28
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Kim KH, Park JY, Park HS, Kim KS, Chin DK, Cho YE, Kuh SU. The Influences of Different Ratios of Biphasic Calcium Phosphate and Collagen Augmentation on Posterior Lumbar Spinal Fusion in Rat Model. Yonsei Med J 2017; 58:407-414. [PMID: 28120573 PMCID: PMC5290022 DOI: 10.3349/ymj.2017.58.2.407] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 10/12/2016] [Accepted: 10/31/2016] [Indexed: 11/27/2022] Open
Abstract
PURPOSE To determine the influence of different ratios of hydroxyapatite (HA)/beta tricalcium phosphate (β-TCP) and collagen augmentation for posterior lumbar fusion in a rat model. MATERIALS AND METHODS We generated a posterior lumbar fusion model in 50 rats and divided it into five groups of equal number as follows; 1) autologous bone graft as group A, 2) 70% HA+30% β-TCP as group B, 3) 70% HA+30% β-TCP+collagen as group C, 4) 30% HA+70% β-TCP as group D, and 5) 30% HA+70% β-TCP+collagen as group E. Rats were euthanized at 12 weeks after surgery and fusion was assessed by manual palpation, quantitative analysis using microCT and histology. RESULTS The score of manual palpation was significantly higher in group C than group E (3.1±1.1 vs. 1.8±0.8, p=0.033). However, in terms of microCT analysis, group D showed significantly higher scores than group B (5.5±0.8 vs. 3.1±1.1, p=0.021). According to quantitative volumetric analysis, 30% HA+70% β-TCP groups (group D and E) showed significantly reduced fusion mass at 12 weeks after surgery (123±14.2, 117±46.3 vs. 151±27.3, p=0.008, 0.003, respectively). Collagen augmentation groups revealed superior results in terms of both microCT score and histologic grade. CONCLUSION A 7:3 HA/β-TCP ratio with collagen augmentation rather than a 3:7 HA/β-TCP ratio could be a more favorable graft substitute for lumbar spinal fusion. There was positive role of collagen as an adjunct for spinal bone fusion process.
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Affiliation(s)
- Kyung Hyun Kim
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Jeong Yoon Park
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Hyo Suk Park
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Keun Su Kim
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Kyu Chin
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Eun Cho
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Uk Kuh
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Seoul, Korea.
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29
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Mesenchymal Stem Cells for the Treatment of Spinal Arthrodesis: From Preclinical Research to Clinical Scenario. Stem Cells Int 2017; 2017:3537094. [PMID: 28286524 PMCID: PMC5327761 DOI: 10.1155/2017/3537094] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Accepted: 01/05/2017] [Indexed: 02/07/2023] Open
Abstract
The use of spinal fusion procedures has rapidly augmented over the last decades and although autogenous bone graft is the “gold standard” for these procedures, alternatives to its use have been investigated over many years. A number of emerging strategies as well as tissue engineering with mesenchymal stem cells (MSCs) have been planned to enhance spinal fusion rate. This descriptive systematic literature review summarizes the in vivo studies, dealing with the use of MSCs in spinal arthrodesis surgery and the state of the art in clinical applications. The review has yielded promising evidence supporting the use of MSCs as a cell-based therapy in spinal fusion procedures, thus representing a suitable biological approach able to reduce the high cost of osteoinductive factors as well as the high dose needed to induce bone formation. Nevertheless, despite the fact that MSCs therapy is an interesting and important opportunity of research, in this review it was detected that there are still doubts about the optimal cell concentration and delivery method as well as the ideal implantation techniques and the type of scaffolds for cell delivery. Thus, further inquiry is necessary to carefully evaluate the clinical safety and efficacy of MSCs use in spine fusion.
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30
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NaPier Z, Kanim LE, Thordarson S, Kropf MA, Cuéllar JM, Glaeser JD, Bae HW. Demineralized Bone Matrix Bone Biology and Clinical Use. ACTA ACUST UNITED AC 2016. [DOI: 10.1053/j.semss.2016.08.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Ajiboye RM, Eckardt MA, Hamamoto JT, Plotkin B, Daubs MD, Wang JC. Outcomes of Demineralized Bone Matrix Enriched with Concentrated Bone Marrow Aspirate in Lumbar Fusion. Int J Spine Surg 2016; 10:35. [PMID: 27909656 DOI: 10.14444/3035] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Multiple studies have demonstrated that a significant amount of variability exists in various demineralized bone matrix (DBM) formulations, which casts doubts on its reliability in consistently promoting fusion. Bone marrow aspirate (BMA) is a cellular based graft that contains mesenchymal stem cells (MSCs) and growth factors can confer osteogenic and osteoinductive potential to DBM. The goal of this study was to describe the outcome of DBM enriched with concentrated BMA in patients undergoing combined lumbar interbody and posterolateral fusion. METHODS Eighty patients with a minimum of 12 months of follow-up were evaluated. Fusion and rates of complication were evaluated. Functional outcomes were assessed based on the modified Odom's criteria. Multiple logistic regression analysis was used to examine the effects of independent variables on fusion outcome. RESULTS The overall rate of solid fusion (i.e patients with both solid posterolateral and interbody fusion) was 81.3% (65/80). Specifically, the radiographic evidence of solid posterolateral and interbody fusions were 81.3% (65/80) and 92.5% (74/80), respectively. Seven (8.75%) patients developed hardware-related complications, 2 (2.5%) patients developed a postoperative infection and 2 (2.5%) patients developed clinical pseudarthrosis. Charlson comorbidity index (CCI) scores of 3 and 4 were associated with non-solid unions (CCI-3, p = 0.048; CCI-4, p = 0.03). Excellent or good outcomes were achieved in 58 (72.5%) patients. CONCLUSIONS Patients undergoing lumbar fusion using an enriched bone graft containing concentrated BMA added to DBM can achieve successful fusion with relatively low complications and good functional outcomes. Despite these findings, more studies with higher level of evidence are needed to better understand the efficacy of this promising graft option.
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Affiliation(s)
- Remi M Ajiboye
- UCLA Medical Center, Department of Orthopaedic Surgery, Santa Monica, CA
| | - Mark A Eckardt
- UCLA Medical Center, Department of Orthopaedic Surgery, Santa Monica, CA
| | - Jason T Hamamoto
- UCLA Medical Center, Department of Orthopaedic Surgery, Santa Monica, CA
| | - Benjamin Plotkin
- UCLA Medical Center, Department of Orthopaedic Surgery, Santa Monica, CA
| | - Michael D Daubs
- University of Nevada School of Medicine, Department of Orthopaedic Surgery, Las Vegas, NV
| | - Jeffrey C Wang
- Keck Medicine of USC, Department of Orthopaedic Surgery, Los Angeles, CA
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Kadam A, Millhouse PW, Kepler CK, Radcliff KE, Fehlings MG, Janssen ME, Sasso RC, Benedict JJ, Vaccaro AR. Bone substitutes and expanders in Spine Surgery: A review of their fusion efficacies. Int J Spine Surg 2016; 10:33. [PMID: 27909654 DOI: 10.14444/3033] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
STUDY DESIGN A narrative review of literature. OBJECTIVE This manuscript intends to provide a review of clinically relevant bone substitutes and bone expanders for spinal surgery in terms of efficacy and associated clinical outcomes, as reported in contemporary spine literature. SUMMARY OF BACKGROUND DATA Ever since the introduction of allograft as a substitute for autologous bone in spinal surgery, a sea of literature has surfaced, evaluating both established and newly emerging fusion alternatives. An understanding of the available fusion options and an organized evidence-based approach to their use in spine surgery is essential for achieving optimal results. METHODS A Medline search of English language literature published through March 2016 discussing bone graft substitutes and fusion extenders was performed. All clinical studies reporting radiological and/or patient outcomes following the use of bone substitutes were reviewed under the broad categories of Allografts, Demineralized Bone Matrices (DBM), Ceramics, Bone Morphogenic proteins (BMPs), Autologous growth factors (AGFs), Stem cell products and Synthetic Peptides. These were further grouped depending on their application in lumbar and cervical spine surgeries, deformity correction or other miscellaneous procedures viz. trauma, infection or tumors; wherever data was forthcoming. Studies in animal populations and experimental in vitro studies were excluded. Primary endpoints were radiological fusion rates and successful clinical outcomes. RESULTS A total of 181 clinical studies were found suitable to be included in the review. More than a third of the published articles (62 studies, 34.25%) focused on BMP. Ceramics (40 studies) and Allografts (39 studies) were the other two highly published groups of bone substitutes. Highest radiographic fusion rates were observed with BMPs, followed by allograft and DBM. There were no significant differences in the reported clinical outcomes across all classes of bone substitutes. CONCLUSIONS There is a clear publication bias in the literature, mostly favoring BMP. Based on the available data, BMP is however associated with the highest radiographic fusion rate. Allograft is also very well corroborated in the literature. The use of DBM as a bone expander to augment autograft is supported, especially in the lumbar spine. Ceramics are also utilized as bone graft extenders and results are generally supportive, although limited. The use of autologous growth factors is not substantiated at this time. Cell matrix or stem cell-based products and the synthetic peptides have inadequate data. More comparative studies are needed to evaluate the efficacy of bone graft substitutes overall.
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Affiliation(s)
- Abhijeet Kadam
- Pennsylvania Hospital of the University of Pennsylvania Health System, Philadelphia, PA
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Ishida W, Elder BD, Holmes C, Lo SFL, Witham TF. Variables Affecting Fusion Rates in the Rat Posterolateral Spinal Fusion Model with Autogenic/Allogenic Bone Grafts: A Meta-analysis. Ann Biomed Eng 2016; 44:3186-3201. [PMID: 27473706 DOI: 10.1007/s10439-016-1701-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 07/21/2016] [Indexed: 01/14/2023]
Abstract
The rat posterolateral spinal fusion model with autogenic/allogenic bone graft (rat PFABG) has been increasingly utilized as an experimental model to assess the efficacy of novel fusion treatments. The objective of this study was to investigate the reliability of the rat PFABG model and examine the effects of different variables on spinal fusion. A web-based literature search from January, 1970 to September, 2015, yielded 26 studies, which included 40 rat PFABG control groups and 449 rats. Data regarding age, weight, sex, and strain of rats, graft volume, graft type, decorticated levels, surgical approach, institution, the number of control rats, fusion rate, methods of fusion assessment, and timing of fusion assessment were collected and analyzed. The primary outcome variable of interest was fusion rate, as evaluated by manual palpation. Fusion rates varied widely, from 0 to 96%. The calculated overall fusion rate was 46.1% with an I 2 value of 62.4, which indicated moderate heterogeneity. Weight >300 g, age >14 weeks, male rat, Sprague-Dawley strain, and autogenic coccyx grafts increased fusion rates with statistical significance. Additionally, an assessment time-point ≥8 weeks had a trend towards statistical significance (p = 0.070). Multi-regression analysis demonstrated that timing of assessment and age as continuous variables, as well as sex as a categorical variable, can predict the fusion rate with R 2 = 0.82. In an inter-institution reliability analysis, the pooled overall fusion rate was 50.0% [44.8, 55.3%], with statistically significant differences among fusion outcomes at different institutions (p < 0.001 and I 2 of 72.2). Due to the heterogeneity of fusion outcomes, the reliability of the rat PFABG model was relatively limited. However, selection of adequate variables can optimize its use as a control group in studies evaluating the efficacy of novel fusion therapies.
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Affiliation(s)
- Wataru Ishida
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA
| | - Benjamin D Elder
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA.
| | - Christina Holmes
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA
| | - Sheng-Fu L Lo
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA
| | - Timothy F Witham
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA
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Stanovici J, Le Nail LR, Brennan MA, Vidal L, Trichet V, Rosset P, Layrolle P. Bone regeneration strategies with bone marrow stromal cells in orthopaedic surgery. Curr Res Transl Med 2016; 64:83-90. [PMID: 27316391 DOI: 10.1016/j.retram.2016.04.006] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 04/13/2016] [Accepted: 04/14/2016] [Indexed: 12/18/2022]
Abstract
Bone is the most transplanted tissue human with 1 million procedures every year in Europe. Surgical interventions for bone repair are required for varied reasons such as trauma resulting non-union fractures, or diseases including osteoporosis or osteonecrosis. Autologous bone grafting is the gold standard in bone regeneration but it requires a second surgery with associated pain and complications, and is also limited by harvested bone quantity. Synthetic bone substitutes lack the osteoinductive properties to heal large bone defects. Cell therapies based on bone marrow or ex vivo expanded mesenchymal stromal stem cells (MSCs) in association with synthetic calcium phosphate (CaP) bone substitutes may be alternatives to autologous bone grafting. This manuscript reviews the different conventional biological and synthetic bone grafting procedures as well as the more recently introduced cell therapy approaches used in orthopaedic surgery for bone regeneration. Some clinical studies have demonstrated safety and efficacy of these approaches but regeneration of large bone defects remain challenging due to the absence of rapid and adequate vascularisation. Future directions in the field of bone regeneration are presented, such as testing alternative cell sources or in situ fabrication of vascularized bone grafts in patients.
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Affiliation(s)
- J Stanovici
- Inserm, UMR 957, équipe labellisée Ligue 2012, 1, rue Gaston-Veil, 44035 Nantes, France; Laboratoire de physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, faculté de médecine, université de Nantes, Nantes Atlantique universités, 1, rue Gaston-Veil, 44035 Nantes, France; Service de chirurgie orthopédique et traumatologique 2, hôpital Trousseau, CHRU de Tours, 37044 Tours, France
| | - L-R Le Nail
- Inserm, UMR 957, équipe labellisée Ligue 2012, 1, rue Gaston-Veil, 44035 Nantes, France; Laboratoire de physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, faculté de médecine, université de Nantes, Nantes Atlantique universités, 1, rue Gaston-Veil, 44035 Nantes, France; Service de chirurgie orthopédique et traumatologique 2, hôpital Trousseau, CHRU de Tours, 37044 Tours, France
| | - M A Brennan
- Inserm, UMR 957, équipe labellisée Ligue 2012, 1, rue Gaston-Veil, 44035 Nantes, France; Laboratoire de physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, faculté de médecine, université de Nantes, Nantes Atlantique universités, 1, rue Gaston-Veil, 44035 Nantes, France
| | - L Vidal
- Inserm, UMR 957, équipe labellisée Ligue 2012, 1, rue Gaston-Veil, 44035 Nantes, France; Laboratoire de physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, faculté de médecine, université de Nantes, Nantes Atlantique universités, 1, rue Gaston-Veil, 44035 Nantes, France
| | - V Trichet
- Inserm, UMR 957, équipe labellisée Ligue 2012, 1, rue Gaston-Veil, 44035 Nantes, France; Laboratoire de physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, faculté de médecine, université de Nantes, Nantes Atlantique universités, 1, rue Gaston-Veil, 44035 Nantes, France
| | - P Rosset
- Inserm, UMR 957, équipe labellisée Ligue 2012, 1, rue Gaston-Veil, 44035 Nantes, France; Laboratoire de physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, faculté de médecine, université de Nantes, Nantes Atlantique universités, 1, rue Gaston-Veil, 44035 Nantes, France; Service de chirurgie orthopédique et traumatologique 2, hôpital Trousseau, CHRU de Tours, 37044 Tours, France
| | - P Layrolle
- Inserm, UMR 957, équipe labellisée Ligue 2012, 1, rue Gaston-Veil, 44035 Nantes, France; Laboratoire de physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, faculté de médecine, université de Nantes, Nantes Atlantique universités, 1, rue Gaston-Veil, 44035 Nantes, France; Service de chirurgie orthopédique et traumatologique 2, hôpital Trousseau, CHRU de Tours, 37044 Tours, France.
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Liu X, Yang L, Li J, Zhang Y, Xu W, Ren Y, Liu B, Yang B, Li B. GS/DBM/PLA porous composite biomaterial for the treatment of infective femoral condyle defect in rats. Exp Ther Med 2016; 11:2107-2116. [PMID: 27284292 PMCID: PMC4887764 DOI: 10.3892/etm.2016.3219] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Accepted: 11/25/2015] [Indexed: 11/06/2022] Open
Abstract
A bone defect resulting from open bone trauma may easily become infected; however, the administration of efficacious systemic antibiotics cannot be performed at safe levels. Previous studies have investigated anti-infective biomaterials that incorporate into bone and facilitate the direct application of high-concentration local antibiotics. In the present study, the effect of a novel porous composite with gentamicin sulfate (GS) in treating infected femoral condyle defects was investigated using a rat model. A novel porous composite biomaterial was prepared based on a supercritical carbon dioxide fluid technique that combined GS, demineralized bone matrix (DBM) and polylactic acid (PLA). A rat femoral condyle fracture model of infection was established. The GS/DBM/PLA composite biomaterial was implanted and its physicochemical characteristics, biocompatibility and ability to facilitate repair of infected bone defect were assessed. The GS/DBM/PLA composite biomaterial maintained the antibiotic activity of GS, with good anti-compression strength, porosity and biocompatibility. The results of the animal experiments indicated that the GS/DBM/PLA composite biomaterial exerted marked anti-infective effects and facilitated bone defect repair, while simultaneously controlling infection. Porous GS/DBM/PLA is therefore a promising composite biomaterial for use in bone tissue engineering.
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Affiliation(s)
- Xiaoming Liu
- Department of Human Anatomy, Guangdong Provincial Key Laboratory of Medical Biomechanics, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China; China Institute for Radiation Protection, Taiyuan, Shanxi 030006, P.R. China
| | - Lin Yang
- Department of Human Anatomy, Zunyi Medical College, Zhuhai, Guangdong 519041, P.R. China
| | - Jing Li
- China Institute for Radiation Protection, Taiyuan, Shanxi 030006, P.R. China
| | - Yuming Zhang
- China Institute for Radiation Protection, Taiyuan, Shanxi 030006, P.R. China
| | - Weijun Xu
- China Institute for Radiation Protection, Taiyuan, Shanxi 030006, P.R. China
| | - Yan Ren
- Department of Medical Imaging, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Biwang Liu
- Department of Traditional Chinese Medicine, Shanxi University, Taiyuan, Shanxi 030001, P.R. China
| | - Biao Yang
- China Institute for Radiation Protection, Taiyuan, Shanxi 030006, P.R. China
| | - Baoxing Li
- Department of Human Anatomy, Guangdong Provincial Key Laboratory of Medical Biomechanics, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China; China Institute for Radiation Protection, Taiyuan, Shanxi 030006, P.R. China
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Makhni MC, Caldwell JME, Saifi C, Fischer CR, Lehman RA, Lenke LG, Lee FY. Tissue engineering advances in spine surgery. Regen Med 2016; 11:211-22. [DOI: 10.2217/rme.16.3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Autograft, while currently the gold standard for bone grafting, has several significant disadvantages including limited supply, donor site pain, hematoma formation, nerve and vascular injury, and fracture. Bone allografts have their own disadvantages including reduced osteoinductive capability, lack of osteoprogenitor cells, immunogenicity and risk of disease transmission. Thus demand exists for tissue-engineered constructs that can produce viable bone while avoiding the complications associated with human tissue grafts. This review will focus on recent advancements in tissue-engineered bone graft substitutes utilizing nanoscale technology in spine surgery applications. An evaluation will be performed of bone graft substitutes, biomimetic 3D scaffolds, bone morphogenetic protein, mesenchymal stem cells and intervertebral disc regeneration strategies.
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Affiliation(s)
- Melvin C Makhni
- Department of Orthopedic Surgery, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
| | - Jon-Michael E Caldwell
- Department of Orthopedic Surgery, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
| | - Comron Saifi
- The Spine Hospital, Department of Orthopedic Surgery, New York-Presbyterian Healthcare System, Columbia University Medical Center, 5141 Broadway, New York, NY 10034, USA
| | - Charla R Fischer
- The Spine Hospital, Department of Orthopedic Surgery, New York-Presbyterian Healthcare System, Columbia University Medical Center, 5141 Broadway, New York, NY 10034, USA
| | - Ronald A Lehman
- Department of Orthopedic Surgery, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
| | - Lawrence G Lenke
- The Spine Hospital, Department of Orthopedic Surgery, New York-Presbyterian Healthcare System, Columbia University Medical Center, 5141 Broadway, New York, NY 10034, USA
| | - Francis Y Lee
- Department of Orthopedic Surgery, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
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An effect comparison of teriparatide and bisphosphonate on posterior lumbar interbody fusion in patients with osteoporosis: a prospective cohort study and preliminary data. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2015; 26:691-697. [PMID: 26661639 DOI: 10.1007/s00586-015-4342-y] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 11/25/2015] [Accepted: 11/25/2015] [Indexed: 02/01/2023]
Abstract
PURPOSE Our purpose was to evaluate the efficacy of teriparatide for posterior lumbar interbody fusion (PLIF) in osteoporotic women. METHODS Forty-seven osteoporotic patients underwent PLIF with pedicle screw fixation for degenerative lumbar stenosis and instability. Patients were divided into two groups. The teriparatide group (n = 23) was injected subcutaneously with teriparatide (20 μg daily) for 3-month cycles alternating with 3-month periods of oral sodium alendronate for 12 months. The bisphosphonate group (n = 24) was administered oral sodium alendronate (91.37 mg/week) for ≥1 year. Serial plain radiography, computed tomography, and bone mineral densitometry (BMD) evaluations were performed. Fusion rate, bony fusion duration, and T score changes were evaluated. Clinical data [pain scores, Prolo's functional scale, and Oswestry disability index (ODI)] were also serially evaluated. RESULTS The teriparatide group showed earlier fusion than the bisphosphonate group. The average period of bone fusion was 6.0 ± 4.8 months in the teriparatide group but 10.4 ± 7.2 months in the bisphosphonate group. The bone fusion rate in the teriparatide group was higher than that in the bisphosphonate group at 6 months; however, there was no difference 12 and 24 months after surgery. Pain scores and ODI were not significantly different between groups. BMD scores in the teriparatide group were significantly improved compared with the bisphosphonate group 2 years after surgery. CONCLUSIONS There was no significant improvement in overall fusion rate and clinical outcome in our patients after injection of teriparatide, but the teriparatide group showed faster bony union and highly improved BMD scores.
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