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Stadelmann N, Horch RE, Schmid R, Ostendorf D, Peddi A, Promny T, Boos AM, Kengelbach-Weigand A. Growth factors IGF-1 and KGF and adipose-derived stem cells promote migration and viability of primary human keratinocytes in an in vitro wound model. Front Med (Lausanne) 2025; 12:1516116. [PMID: 39981084 PMCID: PMC11839819 DOI: 10.3389/fmed.2025.1516116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/20/2025] [Indexed: 02/22/2025] Open
Abstract
Introduction In the field of plastic surgery, epidermal transplantation is a potential treatment for chronic wounds that results in only minor donor site morbidity. Improving the regenerative capacities of epidermal grafts or single-cell suspensions and therefore accelerating healing processes would be of significant interest. Methods In the present study, we analyzed the effects of growth factors and adipose-derived stem cells (ADSCs) on keratinocyte properties. For optimum translation into the clinical setting, primary human keratinocytes and patient-matched ADSCs were isolated and used in an in vitro wound model. Results The keratinocyte migration and viability increased after treatment with the growth factors insulin-like growth factor 1 (IGF-1) and keratinocyte growth factor (KGF). A similar effect was observed with the use of a concentrated ADSC-conditioned medium (ADSC-CM). It was further possible to isolate the keratinocytes in a xenogen-free medium, which is essential for clinical translation. Importantly, a patient-dependent influence on the effects of the growth factors and ADSC-CM was observed. Discussion This study provides potential for the improvement of epidermal transplantation in the treatment of chronic wounds using xenogen-free isolated and cultivated keratinocytes, growth factors, and ADSC. Translating these results into clinical application may help accelerate wound healing and shorten the time until patients can return to everyday life.
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Affiliation(s)
| | - Raymund E. Horch
- Department of Plastic and Hand Surgery and Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital of Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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Yerebakan M, Tuter G, Bagriacik EU, Oruklu N, Guldurur T. Evaluation of the anti-inflammatory, antioxidant and wound healing effects of pterostilbene in human gingival fibroblasts in vitro. Odontology 2025:10.1007/s10266-024-01052-7. [PMID: 39836293 DOI: 10.1007/s10266-024-01052-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 12/30/2024] [Indexed: 01/22/2025]
Abstract
We aimed to investigate the wound-healing, antioxidant, and anti-inflammatory effects of pterostilbene (PTS) on human gingival fibroblasts (GF). Different concentrations of PTS were applied to GFs and cell viability was evaluated by MTT assay. GFs were stimulated by lipopolysaccharide (LPS) and the study groups were determined as LPS, LPS + 1 μM PTS, LPS + 10 μM PTS, and control. The most effective PTS concentrations were applied in a wound-healing model, with cell counts in the wound area assessed at 0, 24, 48, and 72 h. The effect of PTS on the release of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), basic fibroblast growth factor (bFGF), and collagen type I (COL I) was assessed at 24 and 48 h by ELISA. The data was statistically analyzed. Our results showed that PTS had a dose-dependently negative effect on wound healing and cell proliferation at 10 μM concentration, but not at low concentration (1 μM). PTS exhibited a potent anti-inflammatory effect by reducing IL-6 and TNF-α levels, while also enhancing antioxidant activity, as evidenced by increased GSH-Px levels in the LPS + 1 μM PTS group (P < 0.05). According to our results, PTS could be a potential and promising substance with anti-inflammatory and antioxidant effects on LPS-stimulated GF. Therefore our results have merit in terms of providing pioneering data for future studies.
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Affiliation(s)
- Mukaddes Yerebakan
- Department of Periodontology, Faculty of Dentistry, Gazi University, Ankara, Turkey
| | - Gulay Tuter
- Department of Periodontology, Faculty of Dentistry, Gazi University, Ankara, Turkey.
| | - Emin Umit Bagriacik
- Department of Immunology, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Nihan Oruklu
- Department of Immunology, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Tugce Guldurur
- Department of Periodontology, Faculty of Dentistry, Gazi University, Ankara, Turkey
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Polizzi A, Leanza Y, Belmonte A, Grippaudo C, Leonardi R, Isola G. Impact of Hyaluronic Acid and Other Re-Epithelializing Agents in Periodontal Regeneration: A Molecular Perspective. Int J Mol Sci 2024; 25:12347. [PMID: 39596411 PMCID: PMC11594871 DOI: 10.3390/ijms252212347] [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: 09/26/2024] [Revised: 11/11/2024] [Accepted: 11/15/2024] [Indexed: 11/28/2024] Open
Abstract
This narrative review delves into the molecular mechanisms of hyaluronic acid (HA) and re-epithelializing agents in the context of periodontal regeneration. Periodontitis, characterized by chronic inflammation and the destruction of tooth-supporting tissues, presents a significant challenge in restorative dentistry. Traditional non-surgical therapies (NSPTs) sometimes fail to fully manage subgingival biofilms and could benefit from adjunctive treatments. HA, with its antibacterial, antifungal, anti-inflammatory, angiogenic, and osteoinductive properties, offers promising therapeutic potential. This review synthesizes the current literature on the bioactive effects of HA and re-epithelializing agents, such as growth factors and biomaterials, in promoting cell migration, proliferation, and extracellular matrix (ECM) synthesis. By modulating signaling pathways like the Wnt/β-catenin, TGF-β, and CD44 interaction pathways, HA enhances wound healing processes and tissue regeneration. Additionally, the role of HA in facilitating cellular crosstalk between epithelial and connective tissues is highlighted, as it impacts the inflammatory response and ECM remodeling. This review also explores the combined use of HA with growth factors and cytokines in wound healing, revealing how these agents interact synergistically to optimize periodontal regeneration. Future perspectives emphasize the need for further clinical trials to evaluate the long-term outcomes of these therapies and their potential integration into periodontal treatment paradigms.
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Affiliation(s)
- Alessandro Polizzi
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via S. Sofia 68, 95124 Catania, Italy
| | - Ylenia Leanza
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via S. Sofia 68, 95124 Catania, Italy
| | - Antonio Belmonte
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via S. Sofia 68, 95124 Catania, Italy
| | - Cristina Grippaudo
- Head and Neck Department, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
| | - Rosalia Leonardi
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via S. Sofia 68, 95124 Catania, Italy
| | - Gaetano Isola
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via S. Sofia 68, 95124 Catania, Italy
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Gottardo A, Tulone G, Pavan N, Fulfaro F, Gristina V, Bazan Russo TD, Prestifilippo O, Claps F, Incorvaia L, Galvano A, Russo A, Simonato A. Applications of Platelet Concentrates (PCs) in Regenerative Onco-Urology: A Systematic Review of Literature. Int J Mol Sci 2024; 25:10683. [PMID: 39409012 PMCID: PMC11477022 DOI: 10.3390/ijms251910683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/19/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Objective: To assess the effectiveness of Platelet Concentrates (PCs) in the contest of Hemorrhagic, Actinic, and Radiation Cystitis, plus Urethral Obstruction or Stenosis. Eligibility criteria: Open article in English or Italian regarding in situ applications of PCs for the selected pathologies. Information sources: MEDLINE, Cochrane Library, and ELSEVIER. Risk of bias: High (and discussed). Methods for synthesis of results: Selection of relevant contents, resumed by digital tools, checked by authors and used throughout the manuscript. Included studies: 13 screened articles + 7 personal sources + 37 "extra" articles. Synthesis of results: Pre-clinical and clinical studies demonstrated substantial symptom relief, mucosal restoration, and improved growth factor levels, reducing recurrence rates and complications. However, preparation protocols and results varied among studies. Limitations of evidence: Frequent low-quality studies with mall sample size, plus heterogeneous experimental setups and nomenclature/preparations. Interpretation: PCs demonstrate promise due to their bioactive components, enhancing tissue repair and reducing inflammation with no significant adverse events. Despite positive outcomes in pre-clinical and clinical studies, variability in preparation protocols and small sample sizes, together with inconsistent results, highlight the need for high-quality research to validate PCs' clinical efficacy and cost-effectiveness.
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Affiliation(s)
- Andrea Gottardo
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Gabriele Tulone
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Nicola Pavan
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Fabio Fulfaro
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Valerio Gristina
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Tancredi Didier Bazan Russo
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Ornella Prestifilippo
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Francesco Claps
- Urology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy;
| | - Lorena Incorvaia
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Antonio Galvano
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Antonio Russo
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
| | - Alchiede Simonato
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy; (A.G.); (G.T.); (F.F.); (V.G.); (T.D.B.R.); (O.P.); (L.I.); (A.G.); (A.R.); (A.S.)
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Vlashi R, Zhang X, Li H, Chen G. Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing. Rev Endocr Metab Disord 2024; 25:339-367. [PMID: 38055160 DOI: 10.1007/s11154-023-09860-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/28/2023] [Indexed: 12/07/2023]
Abstract
Osteoarthritis (OA) is an incapacitating and one of the most common physically degenerative conditions with an assorted etiology and a highly complicated molecular mechanism that to date lacks an efficient treatment. The capacity to design biological networks and accurately modify existing genomic sites holds an apt potential for applications across medical and biotechnological sciences. One of these highly specific genomes editing technologies is the CRISPR/Cas9 mechanism, referred to as the clustered regularly interspaced short palindromic repeats, which is a defense mechanism constituted by CRISPR associated protein 9 (Cas9) directed by small non-coding RNAs (sncRNA) that bind to target DNA through Watson-Crick base pairing rules where subsequent repair of the target DNA is initiated. Up-to-date research has established the effectiveness of the CRISPR/Cas9 mechanism in targeting the genetic and epigenetic alterations in OA by suppressing or deleting gene expressions and eventually distributing distinctive anti-arthritic properties in both in vitro and in vivo osteoarthritic models. This review aims to epitomize the role of this high-throughput and multiplexed gene editing method as an analogous therapeutic strategy that could greatly facilitate the clinical development of OA-related treatments since it's reportedly an easy, minimally invasive technique, and a comparatively less painful method for osteoarthritic patients.
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Affiliation(s)
- Rexhina Vlashi
- College of Life Science and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Xingen Zhang
- Department of Orthopedics, Jiaxing Key Laboratory for Minimally Invasive Surgery in Orthopaedics & Skeletal Regenerative Medicine, Zhejiang Rongjun Hospital, Jiaxing, 314001, China
| | - Haibo Li
- The Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children's Hospital, Ningbo, China.
- Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases, Ningbo Women and Children's Hospital, Ningbo, China.
| | - Guiqian Chen
- College of Life Science and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
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Sabeti M, Ghobrial D, Zanjir M, da Costa BR, Young Y, Azarpazhooh A. Treatment outcomes of regenerative endodontic therapy in immature permanent teeth with pulpal necrosis: A systematic review and network meta-analysis. Int Endod J 2024; 57:238-255. [PMID: 37966465 DOI: 10.1111/iej.13999] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 10/21/2023] [Accepted: 10/25/2023] [Indexed: 11/16/2023]
Abstract
AIM The aim of this study was to assess which treatment modality regarding scaffold selection for immature permanent teeth with pulpal necrosis will be the most successful for regenerative endodontic treatment (RET). METHODOLOGY PubMed, Cochrane, Web of Science and Embase, and additional records until August 2022 were searched providing a total of 3021 articles, and nine of these articles were included for quantitative synthesis. The reviewers selected eligible randomized controlled trials and extracted pertinent data. Network meta-analysis was conducted to estimate treatment effects for primary outcomes (clinical and radiographic healing) and secondary outcomes (apical closure, root length and root wall thickness increase) following RET [mean difference (MD); 95% credible interval (CrI) and surface under the cumulative ranking curve (SUCRA)]. The quality of the included studies was appraised by the revised Cochrane risk of bias tool, and the quality of evidence was assessed using the GRADE approach. RESULTS Six interventions from nine included studies were identified: blood clot scaffold (BC), blood clot scaffold with basic fibroblast growth factor, blood clot scaffold with collagen, platelet pellet, platelet-rich plasma (PRP) and platelet-rich fibrin (PRF). The PRP scaffold showed the greatest increase in root lengthening at 6-12 months (MD = 4.2; 95% CrI, 1.2 to 6.8; SUCRA = 89.0%, very low confidence). PRP or PRF achieved the highest level of success for primary and secondary outcomes at 1-6 and 6-12 months. Blood clot scaffold (with collagen or combined with basic fibroblast growth factor (bFGF)) achieved the highest level of success for secondary outcomes beyond 12 months follow-up. A very low to low quality of evidence suggests that both PRP and PRF exhibit the greatest success evaluating primary and secondary outcomes within 12 months postoperatively compared to the traditional blood clot scaffold protocol. CONCLUSION Limited evidence suggests both PRP and PRF exhibit success in the short-term, not long-term. The value of this information stems in its recommendation for future randomized trials prioritizing both of these materials in their protocol.
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Affiliation(s)
- Mohammad Sabeti
- Department of Preventive and Restorative Dental Science, UCSF School of Dentistry, San Francisco, California, USA
| | - Daniel Ghobrial
- PG Endodontic Resident, UCSF School of Dentistry, San Francisco, California, USA
| | - Maryam Zanjir
- Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
| | - Bruno R da Costa
- Clinical Epidemiology & Health Care Research, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Yating Young
- UCSF School of Dentistry, San Francisco, California, USA
| | - Amir Azarpazhooh
- Head Division of Endodontics and Research, Director, Department of Dentistry, Faculty of Advanced Training Program in Orofacial, Faculty of Dentistry, University of Toronto, Mount Sinai Hospital, Toronto, Ontario, Canada
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Lee Y, Lim S, Kim JA, Chun YH, Lee HJ. Development of Thiol-Ene Reaction-Based HA Hydrogel with Sustained Release of EGF for Enhanced Skin Wound Healing. Biomacromolecules 2023; 24:5342-5352. [PMID: 37734002 DOI: 10.1021/acs.biomac.3c00810] [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: 09/23/2023]
Abstract
This study develops a novel drug delivery system using a hyaluronic acid (HA) hydrogel for controlled release of epidermal growth factor (EGF) to enhance skin wound healing. Conventional hydrogel-based methods suffer from a burst release and limited drug delivery times. To address this, we employ bioconjugation to introduce an acrylate group to EGF, enabling chemical bonding to the HA hydrogel matrix through thiol-ene cross-linking. This approach results in sustained-release delivery of EGF based on the degradation rate of the HA matrix, overcoming diffusion-based limitations. We confirm the introduction of the acrylate group using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. We evaluated the hydrogel morphology and rheological properties following binding of acrylate-conjugated EGF to the HA matrix. Assessment of the EGF release profile demonstrates delayed release compared to unconjugated EGF. We evaluate the impact on cells through cell proliferation and scratch assays, indicating the system's efficacy. In a rat wound healing model, the sustained release of EGF from the hydrogel system promotes appropriate tissue healing and restores it to a normal state. These findings suggest that this practical drug delivery system, involving the modification of growth factors or drugs to chemically bind healing factors to hydrogels, can achieve long-lasting effects.
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Affiliation(s)
- Yerin Lee
- Department of Chemical and Biological Engineering, Gachon University, 1342 Seongnam-daero, Seongnam-si, Gyeonggi-do 13120, Republic of Korea
| | - Saebin Lim
- Department of Chemical and Biological Engineering, Gachon University, 1342 Seongnam-daero, Seongnam-si, Gyeonggi-do 13120, Republic of Korea
| | - Ji An Kim
- Department of Pediatrics, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Republic of Korea
| | - Yoon Hong Chun
- Department of Pediatrics, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Republic of Korea
| | - Hyun Jong Lee
- Department of Chemical and Biological Engineering, Gachon University, 1342 Seongnam-daero, Seongnam-si, Gyeonggi-do 13120, Republic of Korea
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Wang Y, Li J. Current progress in growth factors and extracellular vesicles in tendon healing. Int Wound J 2023; 20:3871-3883. [PMID: 37291064 PMCID: PMC10588330 DOI: 10.1111/iwj.14261] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Accepted: 05/20/2023] [Indexed: 06/10/2023] Open
Abstract
Tendon injury healing is a complex process that involves the participation of a significant number of molecules and cells, including growth factors molecules in a key role. Numerous studies have demonstrated the function of growth factors in tendon healing, and the recent emergence of EV has also provided a new visual field for promoting tendon healing. This review examines the tendon structure, growth, and development, as well as the physiological process of its healing after injury. The review assesses the role of six substances in tendon healing: insulin-like growth factor-I (IGF-I), transforming growth factor β (TGFβ), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and EV. Different growth factors are active at various stages of healing and exhibit separate physiological activities. IGF-1 is expressed immediately after injury and stimulates the mitosis of various cells while suppressing the response to inflammation. VEGF, which is also active immediately after injury, accelerates local metabolism by promoting vascular network formation and positively impacts the activities of other growth factors. However, VEGF's protracted action could be harmful to tendon healing. PDGF, the earliest discovered cytokine to influence tendon healing, has a powerful cell chemotaxis and promotes cell proliferation, but it can equally accelerate the response to inflammation and relieve local adhesions. Also useful for relieving tendon adhesion is TGF- β, which is active almost during the entire phase of tendon healing. As a powerful active substance, in addition to its participation in the field of cardiovascular and cerebrovascular vessels, tumour and chronic wounds, TGF- β reportedly plays a role in promoting cell proliferation, activating growth factors, and inhibiting inflammatory response during tendon healing.
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Affiliation(s)
- Yufeng Wang
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin Li
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Peterson KS, Vacketta V, Kavanagh A. The Ankle Joint: Non-Operative Updates in Ankle Arthritis, Are Biologics Working? Clin Podiatr Med Surg 2023; 40:669-680. [PMID: 37716744 DOI: 10.1016/j.cpm.2023.05.009] [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] [Indexed: 09/18/2023]
Abstract
The vast majority of ankle arthritis is post-traumatic in nature, with rates of 60% to 80%. Symptoms include pain, decreased range of motion, and joint effusion. Diagnostic imaging is helpful in determining the degree of joint degeneration, with MRI and CT scan being the most sensitive. Conservative treatment modalities are targeted at reducing symptoms and improving function. Injectable therapy has gained popularity over the last few decades, with advancements in biologic treatments. Corticosteroids, hyaluronic acid, platelet-rich plasma, and amniotic tissue-derived products can be used to reduce inflammation in the joint, as well as prevent cartilage degeneration.
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Affiliation(s)
- Kyle S Peterson
- Suburban Orthopaedics, 1110 West Schick Road, Bartlett, IL 60103, USA.
| | - Vincent Vacketta
- Orthopedic Foot and Ankle Center Fellowship, 350 West Wilson Bridge Road, Suite. 200, Worthington, OH 43085, USA
| | - Amber Kavanagh
- Hinsdale Orthopaedics (IBJI) Foot and Ankle Fellowship, 951 Essington Road, Joliet, IL 60435, USA
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Pretorius J, Habash M, Ghobrial B, Alnajjar R, Ellanti P. Current Status and Advancements in Platelet-Rich Plasma Therapy. Cureus 2023; 15:e47176. [PMID: 38021947 PMCID: PMC10652151 DOI: 10.7759/cureus.47176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2023] [Indexed: 12/01/2023] Open
Abstract
Platelet-rich plasma (PRP) as a treatment modality has been around for the last four decades, but only truly gained popularity over the last 10 to 15 years in medicine, in a variety of fields ranging from regenerative medicine to infertility treatment. It has gained popularity, especially in treating musculoskeletal conditions where the bulk of research has been performed and published. There is level I evidence available supporting its efficacy in the treatment of osteoarthritis (OA), epicondylitis, bursitis, compressive neuropathy, plantar fasciitis, muscular injuries and osteochondral lesions. Most published research with regards to PRP has been focused on knee OA (limited research in shoulder, elbow, and foot and ankle OA), lateral epicondylitis and carpal tunnel syndrome, whereas spinal and hand conditions have limited research available. Tendinopathies and partial tendon tears have conflicting evidence available, with level I evidence supporting PRP's use in rotator cuff tendinopathies and tears, with contradictory level I evidence discouraging its use in patella and Achilles tendinopathies and tears. The available evidence regarding the use of PRP continues to produce conflicting results, but despite this, there is an ongoing increase in the popularity and use of PRP in patients with musculoskeletal conditions.
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Affiliation(s)
| | - Mohammed Habash
- Orthopaedics and Traumatology, University Hospital Galway, Galway, IRL
| | - Bishoy Ghobrial
- Trauma and Orthopaedics, University Hospital Galway, Galway, IRL
| | - Rafee Alnajjar
- Trauma and Orthopaedics, University Hospital Galway, Galway, IRL
| | - Prasad Ellanti
- Trauma and Orthopaedics, Letterkenny University Hospital, Letterkenny, IRL
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Scarneo S, Zhang X, Wang Y, Camacho-Domenech J, Ricano J, Hughes P, Haystead T, Nackley AG. Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain. THE JOURNAL OF PAIN 2023; 24:1633-1644. [PMID: 37121498 PMCID: PMC10524186 DOI: 10.1016/j.jpain.2023.04.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 04/07/2023] [Accepted: 04/24/2023] [Indexed: 05/02/2023]
Abstract
The origin of chronic pain is linked to inflammation, characterized by increased levels of proinflammatory cytokines in local tissues and systemic circulation. Transforming growth factor beta-activated kinase 1 (TAK1) is a key regulator of proinflammatory cytokine signaling that has been well characterized in the context of cancer and autoimmune disorders, yet its role in chronic pain is less clear. Here, we evaluated the ability of our TAK1 small-molecule inhibitor, takinib, to attenuate pain and inflammation in preclinical models of inflammatory, neuropathic, and primary pain. Inflammatory, neuropathic, and primary pain was modeled using intraplantar complete Freund's adjuvant (CFA), chronic constriction injury (CCI), and systemic delivery of the catechol-O-methyltransferase (COMT) inhibitor OR486, respectively. Behavioral responses evoked by mechanical and thermal stimuli were evaluated in separate groups of mice receiving takinib or vehicle prior to pain induction (baseline) and over 12 days following CFA injection, 4 weeks following CCI surgery, and 6 hours following OR486 delivery. Hindpaw edema was also measured prior to and 3 days following CFA injection. Upon termination of behavioral experiments, dorsal root ganglia (DRG) were collected to measure cytokines. We also evaluated the ability of takinib to modulate nociceptor activity via in vitro calcium imaging of neurons isolated from the DRG of Gcamp3 mice. In all 3 models, TAK1 inhibition significantly reduced hypersensitivity to mechanical and thermal stimuli and expression of proinflammatory cytokines in DRG. Furthermore, TAK1 inhibition significantly reduced the activity of tumor necrosis factor (TNF)-primed/capsaicin-evoked DRG nociceptive neurons. Overall, our results support the therapeutic potential of TAK1 as a novel drug target for the treatment of chronic pain syndromes with different etiologies. PERSPECTIVE: This article reports the therapeutic potential of TAK1 inhibitors for the treatment of chronic pain. This new treatment has the potential to provide a greater therapeutic offering to physicians and patients suffering from chronic pain as well as reduce the dependency on opioid-based pain treatments.
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Affiliation(s)
- Scott Scarneo
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina; EydisBio Inc., Department of Research and Development Durham, North Carolina.
| | - Xin Zhang
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina; Department of Anesthesiology, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi, Jiangsu, China
| | - Yaomin Wang
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina
| | - Jose Camacho-Domenech
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina
| | - Jennifer Ricano
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina
| | - Philip Hughes
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina; EydisBio Inc., Department of Research and Development Durham, North Carolina
| | - Tim Haystead
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina; EydisBio Inc., Department of Research and Development Durham, North Carolina
| | - Andrea G Nackley
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina
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Iacopetti I, Perazzi A, Patruno M, Contiero B, Carolo A, Martinello T, Melotti L. Assessment of the quality of the healing process in experimentally induced skin lesions treated with autologous platelet concentrate associated or unassociated with allogeneic mesenchymal stem cells: preliminary results in a large animal model. Front Vet Sci 2023; 10:1219833. [PMID: 37559892 PMCID: PMC10407250 DOI: 10.3389/fvets.2023.1219833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 07/13/2023] [Indexed: 08/11/2023] Open
Abstract
Regenerative medicine for the treatment of skin lesions is an innovative and rapidly developing field that aims to promote wound healing and restore the skin to its original condition before injury. Over the years, different topical treatments have been evaluated to improve skin wound healing and, among them, mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) have shown promising results for this purpose. This study sought to evaluate the quality of the healing process in experimentally induced full-thickness skin lesions treated with PRP associated or unassociated with MSCs in a sheep second intention wound healing model. After having surgically created full-thickness wounds on the back of three sheep, the wound healing process was assessed by performing clinical evaluations, histopathological examinations, and molecular analysis. Treated wounds showed a reduction of inflammation and contraction along with an increased re-epithelialization rate and better maturation of the granulation tissue compared to untreated lesions. In particular, the combined treatment regulated the expression of collagen types I and III resulting in a proper resolution of the granulation tissue contrary to what was observed in untreated wounds; moreover, it led to a better maturation and organization of skin adnexa and collagen fibers in the repaired skin compared to untreated and PRP-treated wounds. Overall, both treatments improved the wound healing process compared to untreated wounds. Wounds treated with PRP and MSCs showed a healing progression that qualitatively resembles a restitutio ad integrum of the repaired skin, showing features typical of a mature healthy dermis.
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Affiliation(s)
- Ilaria Iacopetti
- Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy
| | - Anna Perazzi
- Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy
| | - Marco Patruno
- Department of Comparative Biomedicine and Food Science, University of Padua, Padova, Italy
| | - Barbara Contiero
- Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy
| | - Anna Carolo
- Department of Comparative Biomedicine and Food Science, University of Padua, Padova, Italy
| | | | - Luca Melotti
- Department of Comparative Biomedicine and Food Science, University of Padua, Padova, Italy
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Prospective use of amniotic mesenchymal stem cell metabolite products for tissue regeneration. J Biol Eng 2023; 17:11. [PMID: 36759827 PMCID: PMC9912508 DOI: 10.1186/s13036-023-00331-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
Chronic disease can cause tissue and organ damage constituting the largest obstacle to therapy which, in turn, reduces patients' quality-adjusted life-year. Degenerative diseases such as osteoporosis, Alzheimer's disease, Parkinson's disease, and infectious conditions such as hepatitis, cause physical injury to organs. Moreover, damage resulting from chronic conditions such as diabetes can also culminate in the loss of organ function. In these cases, organ transplantation constitutes the therapy of choice, despite the associated problems of immunological rejection, potential disease transmission, and high morbidity rates. Tissue regeneration has the potential to heal or replace tissues and organs damaged by age, disease, or trauma, as well as to treat disabilities. Stem cell use represents an unprecedented strategy for these therapies. However, product availability and mass production remain challenges. A novel therapeutic alternative involving amniotic mesenchymal stem cell metabolite products (AMSC-MP) has been developed using metabolites from stem cells which contain cytokines and growth factors. Its potential role in regenerative therapy has recently been explored, enabling broad pharmacological applications including various gastrointestinal, lung, bladder and renal conditions, as well as the treatment of bone wounds, regeneration and skin aging due to its low immunogenicity and anti-inflammatory effects. The various kinds of growth factors present in AMSC-MP, namely bFGF, VEGF, TGF-β, EGF and KGF, have their respective functions and activities. Each growth factor is formed by different proteins resulting in molecules with various physicochemical properties and levels of stability. This knowledge will assist in the manufacture and application of AMSC-MP as a therapeutic agent.
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Regulatory Considerations of Orthobiologic Procedures. Phys Med Rehabil Clin N Am 2023; 34:275-283. [DOI: 10.1016/j.pmr.2022.08.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Honbo ES, Mattfeld R, Khadavi M, Podesta L. Clinical Rationale and Rehabilitation Guidelines for Post Biologic Therapy. Phys Med Rehabil Clin N Am 2023; 34:239-263. [DOI: 10.1016/j.pmr.2022.08.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Wiciński M, Szwedowski D, Wróbel Ł, Jeka S, Zabrzyński J. The Influence of Body Mass Index on Growth Factor Composition in the Platelet-Rich Plasma in Patients with Knee Osteoarthritis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 20:40. [PMID: 36612361 PMCID: PMC9819567 DOI: 10.3390/ijerph20010040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/15/2022] [Accepted: 12/17/2022] [Indexed: 06/17/2023]
Abstract
BACKGROUND An abnormally high body mass index is strongly associated with knee osteoarthritis. Usually, obese patients are excluded from clinical trials involving PRP intra-articular injections. Growth factors have been demonstrated to have a disease-modifying effect on KOA treatment, even though data on their influence on treatment effectiveness in obese patients are lacking. PURPOSE To prospectively compare the level of selected growth factors including transforming growth factor-b (TGF-β), epidermal growth factor (EGF), fibroblast growth factor, insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) in platelet-rich plasma (PRP) in obese patients and patients with normal BMI. METHODS A total of 49 patients were included in the study according to inclusion and exclusion criteria. The groups strongly differed in body mass index (median values 21.6 vs. 32.15). Concentrations of growth factors were measured with an enzyme-linked immunosorbent assay. Statistical significance was determined with the Mann-Whitney U test. The compliance of the distribution of the results with the normal distribution was checked using the Shapiro-Wilk test separately for both groups. RESULTS There were no statistically significant differences in median marker levels between groups. Statistically significant Pearson correlations were observed between IGF-1 serum level and age (weak negative, r = -0.294, p = 0.041) and gender (moderate positive, r = 0.392, 0.005). CONCLUSIONS BMI does not influence the level of selected growth factors in patients with knee osteoarthritis. Obese and non-obese patients had similar compositions of PDGF, TGF-β, EGF, FGF-2, IGF-1, and VEGF. PRP can be used in both groups with similar effects associated with growth factors' influence on articular cartilage.
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Affiliation(s)
- Michał Wiciński
- Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland
| | - Dawid Szwedowski
- Department of Organic Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Dr. A. Jurasza St. 2, 85-094 Bydgoszcz, Poland
- Orthopedic Arthroscopic Surgery International (O.A.S.I.) Bioresearch Foundation, Gobbi N.P.O., 20133 Milan, Italy
| | - Łukasz Wróbel
- Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland
| | - Sławomir Jeka
- Department of Rheumatology and Connective Tissue Diseases, University Hospital No. 2, Collegium Medicum, Nicolaus Copernicus University, 85168 Bydgoszcz, Poland
| | - Jan Zabrzyński
- Department of General Orthopedics, Musculoskeletal Oncology and Trauma Surgery, University of Medical Sciences, 61-701 Poznan, Poland
- Department of Pathology, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland
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Goto R, Nakahata M, Sakai S. Phenol-Grafted Alginate Sulfate Hydrogel as an Injectable FGF-2 Carrier. Gels 2022; 8:gels8120818. [PMID: 36547342 PMCID: PMC9778324 DOI: 10.3390/gels8120818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/06/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022] Open
Abstract
In the field of tissue engineering, fibroblast growth factor-2 (FGF-2) effectively regenerates damaged tissue and restores its biological function. However, FGF-2 readily diffuses and degrades under physiological conditions. Therefore, methods for the sustained and localized delivery of FGF-2 are needed. Drug delivery systems using hydrogels as carriers have attracted significant interest. Injectable hydrogels with an affinity for FGF-2 are candidates for FGF-2 delivery systems. In this study, we fabricated a hydrogel from phenol-grafted alginate sulfate (AlgS-Ph) and investigated its application to the delivery of FGF-2. The hydrogel was prepared under mild conditions via horseradish peroxidase (HRP)-mediated cross-linking. Surface plasmon resonance (SPR) measurements show that the AlgS-Ph hydrogel has an affinity for FGF-2 in accordance with its degree of sulfation. Conditions for the preparation of the AlgS-Ph hydrogel, including HRP and H2O2 concentrations, are optimized so that the hydrogel can be used as an injectable drug carrier. The hydrogel shows no cytotoxicity when using 10T1/2 cells as a model cell line. The angiogenesis assay shows that FGF-2 released from the AlgS-Ph hydrogel promotes the formation of blood vessels. These results indicate that the AlgS-Ph hydrogel is a suitable candidate for the FGF-2 carrier.
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Affiliation(s)
- Ryota Goto
- Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka 560-8531, Japan
| | - Masaki Nakahata
- Department of Macromolecular Science, Graduate School of Science, Osaka University, Toyonaka 560-0043, Japan
- Correspondence: (M.N.); (S.S.)
| | - Shinji Sakai
- Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka 560-8531, Japan
- Correspondence: (M.N.); (S.S.)
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Piao YL, Zhang CY, Zhang Y, Qian K, Zhou Y, Liu JY, Chang YC, Cho H, Choi D. Wound-Healing Effect of Antheraea pernyi Epidermal Growth Factor. INSECTS 2022; 13:975. [PMID: 36354799 PMCID: PMC9695916 DOI: 10.3390/insects13110975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/27/2022] [Accepted: 10/08/2022] [Indexed: 06/16/2023]
Abstract
To evaluate the wound-healing effect of Antheraea pernyi epidermal growth factor (ApEGF), we performed the sequence analysis, cloning, and prokaryotic expression of cDNA from the ApEGF gene, examined the transcriptional changes, and investigated the wound-healing effect of this protein in cells and rat epidermis. Primers were designed based on available sequence information related to the ApEGF gene in a public database, and part of the ApEGF sequence was obtained. The full-length cDNA sequence of ApEGF was obtained using inverse PCR. The gene sequence fragment of ApEGF was 666 bp in length, encoding 221 amino acids, with a predicted protein mass of 24.19 kD, an isoelectric point of 5.15, and no signal peptide sequence. Sequence homology analysis revealed 86.1% sequence homology with Bombyx mori, 92.7% with Manducal sexta, 92.6% with Trichoplusia ni, and 91.8% with Helicoverpa armigera. ApEGF was truncated and then subjected to prokaryotic expression, isolation, and purification. Truncated ApEGF was used for wound-healing experiments in vitro and in vivo. The results showed that after 48 h, transforming growth factor (TGF)-β1 had 187.32% cell growth effects, and the ApEGF group had 211.15% cell growth compared to the control group in vitro. In rat epidermis, truncated ApEGF showed a significantly better healing effect than the control. This result indicated that ApEGF, which exerted a direct wound-healing effect, could be used in wound-healing therapy.
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Affiliation(s)
- Yu-Lan Piao
- School of Food Engineering, Jilin Agriculture Science and Technology University, Jilin 132109, China
- Jilin Province Sericultural Scientific Research Institute, Jilin 132012, China
| | - Chun-Yang Zhang
- Jilin Province Sericultural Scientific Research Institute, Jilin 132012, China
| | - Yue Zhang
- Jilin Province Sericultural Scientific Research Institute, Jilin 132012, China
| | - Kun Qian
- Jilin Province Sericultural Scientific Research Institute, Jilin 132012, China
| | - Ying Zhou
- Jilin Province Sericultural Scientific Research Institute, Jilin 132012, China
| | - Jun-Yan Liu
- Jilin Province Aikangshou Biotechnology Co., Ltd., Jilin 132012, China
| | - Young-Cheol Chang
- Course of Chemical and Biological Engineering, Division of Sustainable and Environmental Engineering, Muroran Institute of Technology, Muroran 050-8585, Japan
| | - Hoon Cho
- Department of Biochemical & Polymer Engineering, Chosun University, Gwangju 61452, Korea
| | - Dubok Choi
- Faculty of Advanced Industry Convergence, Chosun University, Gwangju 61452, Korea
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Platelet-rich plasma: a comparative and economical therapy for wound healing and tissue regeneration. Cell Tissue Bank 2022; 24:285-306. [PMID: 36222966 PMCID: PMC9555256 DOI: 10.1007/s10561-022-10039-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 09/10/2022] [Indexed: 11/17/2022]
Abstract
Rise in the incidences of chronic degenerative diseases with aging makes wound care a socio-economic burden and unceasingly necessitates a novel, economical, and efficient wound healing treatment. Platelets have a crucial role in hemostasis and thrombosis by modulating distinct mechanistic phases of wound healing, such as promoting and stabilizing the clot. Platelet-rich plasma (PRP) contains a high concentration of platelets than naïve plasma and has an autologous origin with no immunogenic adverse reactions. As a consequence, PRP has gained significant attention as a therapeutic to augment the healing process. Since the past few decades, a robust volume of research and clinical trials have been performed to exploit extensive role of PRP in wound healing/tissue regeneration. Despite these rigorous studies and their application in diversified medical fields, efficacy of PRP-based therapies is continuously questioned owing to the paucity of large samplesizes, controlled clinical trials, and standard protocols. This review systematically delineates the process of wound healing and involvement of platelets in tissue repair mechanisms. Additionally, emphasis is laid on PRP, its preparation methods, handling, classification,application in wound healing, and PRP as regenerative therapeutics combined with biomaterials and mesenchymal stem cells (MSCs).
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Sport-Specific Rehabilitation, but Not PRP Injections, Might Reduce the Re-Injury Rate of Muscle Injuries in Professional Soccer Players: A Retrospective Cohort Study. J Funct Morphol Kinesiol 2022; 7:jfmk7040072. [PMID: 36278733 PMCID: PMC9589983 DOI: 10.3390/jfmk7040072] [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: 08/08/2022] [Revised: 09/14/2022] [Accepted: 09/14/2022] [Indexed: 11/23/2022] Open
Abstract
Platelet-rich plasma (PRP) injections are extremely popular in the management of sports injuries in elite athletes. However, data on the use of various administration protocols of PRP are contradictory. The efficacy of platelet-rich plasma in the treatment of muscle injuries in professional soccer players has to be contextualized within the sport-specific rehabilitation program. Despite the questionable role of PRP, a well-structured rehabilitation program is still regarded as the gold standard. We examined the efficacy of various PRP protocols in the management of muscle injuries in professional soccer players in respect to treatment duration and injury recurrence. A retrospective cohort study. Muscle injuries in professional soccer players (n = 79, height 182.1 ± 5.9 cm, weight 76.8 ± 5.8 kg, BMI 23.1 ± 1.4 kg/m2) from three elite soccer clubs from the Russian Premier League were recorded during the 2018−2019 season. The injuries were graded based on MRI, using the British Athletic Muscle Injury Classification. Treatment protocols included the POLICE regimen, short courses of NSAID administration, and the specific rehabilitation program. The sample group of players were administered PRP injections. The average treatment duration with PRP injection was significantly longer than conventional treatment without PRP, 21.5 ± 15.7 days and 15.3 ± 11.1 days, respectively (p = 0.003). Soccer-specific rehabilitation and obtaining MRI/US before the treatment was associated with significantly reduced injury recurrence rate (p < 0.001). There was no significant difference between the PRP injection protocol applied to any muscle and the treatment duration in respect of grade 2A−2B muscle injuries. The total duration of treatment of type 2A−2B injuries was 15 days among all players. In the group receiving local injections of PRP, the total duration of treatment was 18 days; in the group without PRP injections, the treatment duration was 14 days. In our study, PRP treatment was associated with longer treatment duration, regardless of which muscle was injured. This may reflect the tendency to use PRP in higher-degree injuries. Soccer-specific rehabilitation significantly reduced the injury recurrence rate when compared to the administration of PRP injections. MRI/US imaging before returning to play was also associated with a lower injury recurrence rate. There was no significant difference between the PRP injection protocol applied to any muscle and the treatment duration in treatment of type 2A−2B muscle injuries.
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Tamoxifen Prevents Peritendinous Adhesions: A Preliminary Report. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4250771. [PMID: 36177054 PMCID: PMC9514950 DOI: 10.1155/2022/4250771] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 08/16/2022] [Accepted: 08/24/2022] [Indexed: 11/17/2022]
Abstract
Background Scarless healing comprises the ultimate goal after an injury. Since tendon healing results in a fibrotic scar, an injured tendon can never regain the mechanical potential and strength of its uninjured form. A wide variety of studies focus on the tendon healing with an absent or minimal peritendinous adhesions. However, no simple method has managed it at all. Possible complex actions and peritendinous environmental events take place during the tendon healing process. Tamoxifen (TAM), besides its breast cancer-related usage, is a potent antifibrotic drug. Here, we aimed to reduce the peritendinous adhesion with TAM administration. Methods Achilles tendons of 44 Wistar albino rats were randomly distributed in 4 groups. In group 1, bilateral lower extremities were used as control and sham. Groups 2 and 3 were comprised of low-dose (1 mg/kg) and high-dose (40 mg/kg) systemic administration of TAM, respectively. Group 4 included local administration (1 mg/kg) of TAM. Biomechanical, macroscopical, and histopathological analyses were done and compared statistically. Biomechanically, the maximum force that led to tendon rupture was determined, and tensile force data were recorded via tensile testing device. Macroscopical and histopathological analysis were composed of the quantity, quality, and grade of peritendinous adhesions. Results Macroscopic and histopathologic findings revealed that groups 2 and 3 had a variety of values ranging between slight to severe adhesions. In group 2, almost half of the animals had moderate adhesions, whereas in group 3, the majority of the animals had moderate adhesions. There were no animals with moderate or severe adhesions in group 4. Statistically significant values were calculated between sham and control groups. Biomechanically, group 2 showed the most significant result. The tendons in group 2 had the highest stiffness when maximal force was applied to rupture the tendons. Henceforth, all these consequences were proven statistically. Conclusion We achieved less peritendinous adhesion with the local administration of TAM when compared to systemic administration of TAM. A better understanding of the peritendinous environmental process will reveal to develop new therapies in the prevention of peritendinous adhesions.
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22
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Zheng W, Zhu S, Zhang Y, Wang Z, Liao S, Sun S. Novel application of microdissection tungsten needle in total thyroidectomy with central neck dissection for papillary thyroid carcinoma. Front Surg 2022; 9:896275. [PMID: 36090347 PMCID: PMC9458924 DOI: 10.3389/fsurg.2022.896275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 08/04/2022] [Indexed: 11/16/2022] Open
Abstract
Background Energy-based devices (EBD) have been popularized in thyroidectomy worldwide. Microdissection tungsten needle (MDTN) is characterized by the ultra-sharp tip providing safe and meticulous dissection with effective hemostasis. However, little study has applied MDTN in thyroidectomy. Methods This retrospective study compared clinical data of the patients who underwent total thyroidectomy (TT) with central neck dissection (CND) using MDTN, harmonic scalpel (HS), and conventional electrocautery (CE). We assessed outcomes related to surgical efficacy and safety. The injury degree of tissue was assessed by biochemical indicators and early-stage inflammatory factors in the drainage fluid. Histological sections of the thyroid specimens were evaluated to compare levels of thermal damage by the three EBD. Results There was a significant decrease in the intraoperative blood loss, operation time and 24-hour drainage volume in the MDTN group compared to the CE group. The total drainage volume, duration of drainage, and average length of stay of the MDTN group were less compared to the CE group though they did not reach statistical significance. No disparity was observed between the MDTN group and HS group in these variables. Total costs were not significantly different among these groups. The incidence of recurrent laryngeal nerve (RLN) injury was the lowest using MDTN compared to the CE (P = 0.034) and HS (not significant). No statistical differences were observed among these groups regarding postoperative wound pain and infection, hypoparathyroidism, and postoperative hemorrhage. Analysis of biochemical indicators showed a lower level of hemoglobin in the MDTN and HS group than the CE group (P = 0.046 and 0.038, respectively) and less triglyceride in the HS group than the MDTN and CE group (P = 0.002 and 0.029, respectively) but no significant difference in cholesterol level in these groups. Early-stage inflammatory factors including TNF-α and IL-6 showed significantly higher concentration in the CE group than the MDTN and HS group. Histological sections of thyroid specimens revealed that MDTN caused the lowest degree of thermal damage followed by HS then CE.
Conclusion MDTN exhibited comparable surgical efficacy and safety outcomes as HS in thyroidectomy. Therefore, MDTN is a safe and viable alternative for hemostasis in thyroidectomy.
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Enhanced In Vivo Wound Healing Efficacy of a Novel Hydrogel Loaded with Copper (II) Schiff Base Quinoline Complex (CuSQ) Solid Lipid Nanoparticles. Pharmaceuticals (Basel) 2022; 15:ph15080978. [PMID: 36015126 PMCID: PMC9416780 DOI: 10.3390/ph15080978] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 07/30/2022] [Accepted: 07/31/2022] [Indexed: 11/16/2022] Open
Abstract
Wound dressings created using nanotechnology are known as suitable substrates to speed up the healing of both acute and chronic wounds. Therapeutic substances can be delivered using these materials. In this study, a hydrogel loaded with Cu (II) Schiff base 8-hydroxy quinoline complex (CuSQ) solid lipid nanoparticles (SLN) was formulated to investigate its wound healing potential in an excision wound healing model in rats. The CuSQ SLN were spherical shaped with sizes ranging from 111 to 202 nm and a polydispersity index (PDI) ranging from 0.43 to 0.76, encapsulation efficiency (EE) % between 85 and 88, and zeta potential (ZP) of −11.8 to −40 mV. The formulated hydrogel showed good homogeneity, good stability, and a pH of 6.4 which indicates no skin irritation and had no cytotoxicity on the human skin fibroblast (HSF) cell line. In the in vivo study, animals were placed in five groups: control, standard, plain hydrogel, low dose, and high dose of CuSQ hydrogel. Both doses of CuSQ showed significantly faster healing rates compared to standard and control rats. In addition, the histopathology study showed more collagen, improved angiogenesis, and intact re-epithelization with less inflammation. A significant increase in transforming growth factor-beta1 (TGF-β1) level and increased immune expression of vascular endothelial growth factor (VEGF) by CuSQ treatment validates its role in collagen synthesis, proliferation of fibroblasts and enhancement of angiogenesis. Matrix metalloproteinase-9 (MMP-9) was found to be significantly reduced after CuSQ treatment. Immunohistochemistry of tumor necrosis factor alpha (TNF-α) revealed a marked decrease in inflammation. Thus, we concluded that CuSQ would be a beneficial drug for cutaneous wound healing since it effectively accelerated wound healing through regulation of various cytokines and growth factors.
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Comparing the Efficacy of Intra-Articular Single Platelet-Rich Plasma(PRP) versus Novel Crosslinked Hyaluronic Acid for Early-Stage Knee Osteoarthritis: A Prospective, Double-Blind, Randomized Controlled Trial. Medicina (B Aires) 2022; 58:medicina58081028. [PMID: 36013495 PMCID: PMC9415551 DOI: 10.3390/medicina58081028] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 07/25/2022] [Accepted: 07/28/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Objectives: For the treatment of knee osteoarthritis (OA), intra-articular platelet-rich plasma (PRP) and novel crosslinked single-dose hyaluronic acid (HA) have both been reported to improve outcomes, but no study has compared them for the treatment of knee OA. We hypothesized patients with early-stage knee OA who received PRP injections would have more WOMAC score changes than those who received HA injections. This is the first prospective, double-blind, parallel, randomized controlled trial comparing the efficacy of intra-articular single-dose PRP versus novel crosslinked HA (HyajointPlus) for treating early-stage knee OA. Materials and Methods: This study analyzed 110 patients randomized into the PRP (n = 54) or HA (n = 56) groups. The primary outcome is the change of WOMAC score at 1-, 3-, and 6-month follow-ups compared to baseline. Results: The data revealed significant improvements in all WOMAC scores in the PRP group at 1-, 3-, and 6-month follow-up visits compared with the baseline level except for the WOMAC stiffness score at the 1-month follow up. In the HA group, significant improvements were observed only in the WOMAC pain score for all the follow-up visits and in WOMAC stiffness, function, and total scores at 6-month follow-up. When comparing the change of WOMAC score at 1-, 3-, and 6-month follow-ups, no significant differences were found between PRP and HA group. Conclusions: This study revealed that both PRP and HA can yield significant improvements in WOMAC scores at 6-month follow-up without any between-group differences at 1-, 3-, and 6-month follow-ups. Thus, both the single-injection regimens of PRP and HA can improve the functional outcomes for treating early-stage knee OA.
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Nguyen M, Nguyen TT, Tran HLB, Tran DN, Ngo LTQ, Huynh NC. Effects of advanced platelet-rich fibrin combined with xenogenic bone on human periodontal ligament stem cells. Clin Exp Dent Res 2022; 8:875-882. [PMID: 35338771 PMCID: PMC9382045 DOI: 10.1002/cre2.563] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 03/07/2022] [Accepted: 03/11/2022] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES In this study, we aimed to investigate the effects of a mixture of advanced platelet-rich fibrin (A-PRF) and xenogenic bone substitute material (XBSM) on the proliferation and migration of human periodontal ligament stem cells (hPDLSCs) based on the in vitro release of growth factors. MATERIAL AND METHODS The concentrations of platelet-derived growth factor-AB (PDGF-AB) and vascular endothelial growth factor (VEGF) released by the A-PRF-XBSM mixture were estimated using enzyme-linked immunoassay for up to 7 d. The A-PRF-XBSM mixture exudate was incubated with hPDLSCs. At Days 1, 3, 5, and 7, cell proliferation and migration were investigated by cell counting and wound-healing assays. RESULTS PDGD-AB and VEGF were released from the A-PRF-XBSM mixture exudate for up to 7 days. hPDLSCs were cultured in media with various concentrations of the A-PRF-XBSM mixture exudate and exhibited their proliferation and migration ability. Furthermore, the factors released from the 100% A-PRF-XBSM mixture exudate had a substantial effect on cell migration, whereas those released from 4% and 20% A-PRF-XBSM mixture exudates stimulated hPDLSC proliferation. CONCLUSIONS A-PRF-XBSM mixture continuously released growth factors over 7 days and enhanced hPDLSC proliferation and migration. Therefore, A-PRF in combination with XBSM might provide potential advantages for periodontal tissue regeneration.
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Affiliation(s)
- Meo Nguyen
- Department of Periodontology, Faculty of Odonto‐StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam
| | - Thuy Thu Nguyen
- Department of Periodontology, Faculty of Odonto‐StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam
| | - Ha Le Bao Tran
- Laboratory of Tissue Engineering and Biomedical Materials, Department of Physiology and Animal Biotechnology, Faculty of Biology‐Biotechnology, University of ScienceVietnam National UniversityHo Chi Minh CityVietnam
| | - Dang Ngoc Tran
- Faculty of Public HealthUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam
| | - Lan Thi Quynh Ngo
- Department of Dental Basic Sciences, Faculty of Odonto‐StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam
| | - Nam Cong‐Nhat Huynh
- Department of Dental Basic Sciences, Faculty of Odonto‐StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam
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Therapeutic delivery of nucleic acids for skin wound healing. Ther Deliv 2022; 13:339-358. [PMID: 35975470 DOI: 10.4155/tde-2022-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Though wound care has advanced, treating chronic wounds remains a challenge and there are many clinical issues that must be addressed. Gene therapy is a recent approach to treating chronic wounds that remains in its developmental stage. The limited reports available describe the therapeutic applications of various forms of nucleic acid delivery for treating chronic wounds, including DNA, mRNA, siRNA, miRNA and so on. Though these bioactive molecules represent great therapeutic potential, sustaining their bioactivity in the wound bed is a challenge. To overcome this hurdle, delivery systems are also being widely investigated. In this review, nucleic acid-based therapy and its delivery for treating chronic wounds is discussed in detail.
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Molnar V, Pavelić E, Vrdoljak K, Čemerin M, Klarić E, Matišić V, Bjelica R, Brlek P, Kovačić I, Tremolada C, Primorac D. Mesenchymal Stem Cell Mechanisms of Action and Clinical Effects in Osteoarthritis: A Narrative Review. Genes (Basel) 2022; 13:genes13060949. [PMID: 35741711 PMCID: PMC9222975 DOI: 10.3390/genes13060949] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 05/21/2022] [Accepted: 05/24/2022] [Indexed: 02/04/2023] Open
Abstract
With the insufficient satisfaction rates and high cost of operative treatment for osteoarthritis (OA), alternatives have been sought. Furthermore, the inability of current medications to arrest disease progression has led to rapidly growing clinical research relating to mesenchymal stem cells (MSCs). The availability and function of MSCs vary according to tissue source. The three primary sources include the placenta, bone marrow, and adipose tissue, all of which offer excellent safety profiles. The primary mechanisms of action are trophic and immunomodulatory effects, which prevent the further degradation of joints. However, the function and degree to which benefits are observed vary significantly based on the exosomes secreted by MSCs. Paracrine and autocrine mechanisms prevent cell apoptosis and tissue fibrosis, initiate angiogenesis, and stimulate mitosis via growth factors. MSCs have even been shown to exhibit antimicrobial effects. Clinical results incorporating clinical scores and objective radiological imaging have been promising, but a lack of standardization in isolating MSCs prevents their incorporation in current guidelines.
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Affiliation(s)
- Vilim Molnar
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia; (V.M.); (E.P.); (E.K.); (V.M.); (P.B.)
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Eduard Pavelić
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia; (V.M.); (E.P.); (E.K.); (V.M.); (P.B.)
| | - Kristijan Vrdoljak
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (K.V.); (M.Č.)
| | - Martin Čemerin
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (K.V.); (M.Č.)
| | - Emil Klarić
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia; (V.M.); (E.P.); (E.K.); (V.M.); (P.B.)
| | - Vid Matišić
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia; (V.M.); (E.P.); (E.K.); (V.M.); (P.B.)
| | - Roko Bjelica
- Department of Oral Surgery, School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| | - Petar Brlek
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia; (V.M.); (E.P.); (E.K.); (V.M.); (P.B.)
| | | | | | - Dragan Primorac
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia; (V.M.); (E.P.); (E.K.); (V.M.); (P.B.)
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
- Medical School, University of Split, 21000 Split, Croatia
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
- Medical School, University of Rijeka, 51000 Rijeka, Croatia
- Medical School REGIOMED, 96450 Coburg, Germany
- Eberly College of Science, The Pennsylvania State University, University Park, PA 16802, USA
- The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, CT 06516, USA
- Correspondence:
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Olufade O, Negron G, Berrigan W, Sirutis B, Whitley J, Easley K, Chen Y, Mautner K. Amniotic dehydrated cell and protein concentrate versus corticosteroid in knee osteoarthritis: preliminary findings. Regen Med 2022; 17:431-443. [PMID: 35586982 DOI: 10.2217/rme-2022-0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Objectives: The purpose is to report preliminary data on clinical response to dehydrated cell and protein concentrate (dCPC) versus corticosteroid (CSI). Design: A single-site prospective, randomized controlled single-blinded trial of patients with knee osteoarthritis. Methods: Pain and function were assessed using a visual analog scale (VAS), the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Emory Quality of Life (EQOL) measure at 1, 2, 3, 6, 9 and 12 months. Results: 51 patients were enrolled at the time of analysis (27 dCPC, 24 CSI). Both groups demonstrated improvement on the VAS, KOOS and EQOL. Largest differences were observed at 2 (p = 0.05), 3 (p = 0.012) and 6 months (p < 0.001) with a decrease of 1.66 in VAS at 6 months for dCPC (95% CI: -2.67 to -0.65) and 1.34 (95% CI: -2.37 to -0.3) for CSI. Time-averaged measures showed no difference between groups (p = 0.20). Limited data at 9 and 12 months trended toward improvement in the dCPC group. Conclusion: dCPC products may be used as a treatment for knee osteoarthritis. Larger trials are warranted. Clinical Trial Registration: NCT03710005 (ClinicalTrials.gov).
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Affiliation(s)
- Oluseun Olufade
- Department of Orthopedics, Emory University, Atlanta, GA 30329, USA.,Department of Physical Medicine & Rehabilitation, Emory University, Atlanta, GA 30307, USA
| | - Giorgio Negron
- Department of Physical Medicine & Rehabilitation, Emory University, Atlanta, GA 30307, USA
| | - William Berrigan
- Department of Orthopedics, Emory University, Atlanta, GA 30329, USA
| | - Benjamin Sirutis
- Department of Physical Medicine & Rehabilitation, Emory University, Atlanta, GA 30307, USA
| | - Jeremy Whitley
- Department of Orthopedics, Emory University, Atlanta, GA 30329, USA
| | - Kirk Easley
- Department of Biostatistics & Bioinformatics, Rollins School of Public Health Emory University, Atlanta, GA 30329, USA
| | - Yunyun Chen
- Department of Biostatistics & Bioinformatics, Rollins School of Public Health Emory University, Atlanta, GA 30329, USA
| | - Kenneth Mautner
- Department of Orthopedics, Emory University, Atlanta, GA 30329, USA.,Department of Physical Medicine & Rehabilitation, Emory University, Atlanta, GA 30307, USA
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Lee JH, You HJ, Lee TY, Kang HJ. Current Status of Experimental Animal Skin Flap Models: Ischemic Preconditioning and Molecular Factors. Int J Mol Sci 2022; 23:5234. [PMID: 35563624 PMCID: PMC9103896 DOI: 10.3390/ijms23095234] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/03/2022] [Accepted: 05/06/2022] [Indexed: 11/18/2022] Open
Abstract
Skin flaps are necessary in plastic and reconstructive surgery for the removal of skin cancer, wounds, and ulcers. A skin flap is a portion of skin with its own blood supply that is partially separated from its original position and moved from one place to another. The use of skin flaps is often accompanied by cell necrosis or apoptosis due to ischemia-reperfusion (I/R) injury. Proinflammatory cytokines, such as nuclear factor kappa B (NF-κB), inhibitor of kappa B (IκB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and oxygen free radicals are known causative agents of cell necrosis and apoptosis. To prevent I/R injury, many investigators have suggested the inhibition of proinflammatory cytokines, stem-cell therapies, and drug-based therapies. Ischemic preconditioning (IPC) is a strategy used to prevent I/R injury. IPC is an experimental technique that uses short-term repetition of occlusion and reperfusion to adapt the area to the loss of blood supply. IPC can prevent I/R injury by inhibiting proinflammatory cytokine activity. Various stem cell applications have been studied to facilitate flap survival and promote angiogenesis and vascularization in animal models. The possibility of constructing tissue engineered flaps has also been investigated. Although numerous animal studies have been published, clinical data with regard to IPC in flap reconstruction have never been reported. In this study, we present various experimental skin flap methods, IPC methods, and methods utilizing molecular factors associated with IPC.
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Affiliation(s)
- Ju-Hee Lee
- College of Korean Medicine, Dongguk University, Goyang 10326, Korea;
| | - Hi-Jin You
- Department of Plastic Surgery, Korea University Ansan Hospital, Ansan 15355, Korea; (H.-J.Y.); (T.-Y.L.)
| | - Tae-Yul Lee
- Department of Plastic Surgery, Korea University Ansan Hospital, Ansan 15355, Korea; (H.-J.Y.); (T.-Y.L.)
| | - Hyo Jin Kang
- Biomedical Research Center, Korea University Ansan Hospital, Ansan 15355, Korea
- Core Research and Development Center, Korea University Ansan Hospital, Ansan 15355, Korea
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Cutaneous Wound Healing: A Review about Innate Immune Response and Current Therapeutic Applications. Mediators Inflamm 2022; 2022:5344085. [PMID: 35509434 PMCID: PMC9061066 DOI: 10.1155/2022/5344085] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 12/22/2021] [Accepted: 03/25/2022] [Indexed: 12/22/2022] Open
Abstract
Skin wounds and compromised wound healing are major concerns for the public. Although skin wound healing has been studied for decades, the molecular and cellular mechanisms behind the process are still not completely clear. The systemic responses to trauma involve the body’s inflammatory and immunomodulatory cellular and humoral networks. Studies over the years provided essential insights into a complex and dynamic immunity during the cutaneous wound healing process. This review will focus on innate cell populations involved in the initial phase of this orchestrated process, including innate cells from both the skin and the immune system.
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31
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Effect of Magnetohydrodynamic on Cutaneous Wound Healing in Rat Model. ARCHIVES OF NEUROSCIENCE 2022. [DOI: 10.5812/ans.118387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Exogenous electrical stimulation of the skin may mimic its endogenous bioelectric currents. In this study, a combination of direct current (DC) and magnetic field (MF) was investigated in the excision of the rat wound model. Methods: A circular wound was created on the posterior of the neck, and an electrode was fixed in the wound center. Rats were divided into sham, DC (600 µA), MF (~0.8 T), and magnet-direct current (MDC) groups. The study was conducted in 14 days with 20-min treatment daily. Results: The DC and MDC groups had higher healing percentages (P < 0.01) with mean differences of -13.42 and -15.63, respectively. Direct current on days 2, 5, and 6, and MDC on days 8, 9, 10, 11, 12, and 13 showed higher wound closing. In the DC-treated group, angiogenesis was improved on day 7. In MDC-treated rats, angiogenesis and fibroplasia were improved on day 13. The MF and MDC groups had lower granulation thicknesses on day 7. Granulation thickness increased on day 13 in the MF and MDC groups, while it decreased in the DC group. Direct current treatment improved healing in the first half of the study period, whereas MDC enhanced it in the second half, overtaking DC. From day 7, the magnet group started to overtake the control group slightly in the last four days. Conclusions: To accelerate wound healing, we suggest applying DC in the first days of wounding and MDC in the following days.
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32
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Farrokhi A, Rahavi M, Jo S, Jalili R, Lim CJ, Ghahsary A, Reid GSD. Inflammatory Immune Responses Trigger Rejection of Allogeneic Fibroblasts Transplanted into Mouse Skin. Cell Transplant 2022; 31:9636897221113803. [PMID: 35912954 PMCID: PMC9340901 DOI: 10.1177/09636897221113803] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Fibroblasts, or their homolog stromal cells, are present in most tissues and play an essential role in tissue homeostasis and regeneration. As a result, fibroblast-based strategies have been widely employed in tissue engineering. However, while considered to have immunosuppressive properties, the survival and functionality of allogeneic fibroblasts after transplantation remain controversial. Here, we evaluated innate and adaptive immune responses against allogeneic fibroblasts following intradermal injection into different immune-deficient mouse strains. While allogeneic fibroblasts were rejected 1 week after transplantation in immunocompetent mice, rejection did not occur in immunodeficient γ chain–deficient NOD-SCID (NSG) mice. T-cell- and B-cell-deficient RAG1 knockout mice showed greater loss of fibroblasts by day 5 after transplantation compared with NSG mice (P ≤ 0.05) but prolonged persistence compared with wild-type recipient (P ≤ 0.005). Loss of fibroblasts correlated with the expression of proinflammatory chemokine genes and infiltration of myeloid cells in the transplantation site. Depletion of macrophages and neutrophils delayed rejection, revealing the role of innate immune cells in an early elimination of fibroblasts that is followed by T-cell-mediated rejection in the second week. These findings indicate that the application of allogeneic fibroblasts in tissue engineering products requires further improvements to overcome cell rejection by innate and adaptive immune cells.
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Affiliation(s)
- Ali Farrokhi
- Michael Cuccione Childhood Cancer Research Program, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Department of Pediatrics, The University of British Columbia, Vancouver, BC, Canada
| | - MohammadReza Rahavi
- Michael Cuccione Childhood Cancer Research Program, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
| | - Sumin Jo
- Michael Cuccione Childhood Cancer Research Program, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
| | - Reza Jalili
- Burn & Wound Healing Research Group, Division of Plastic Surgery, Department of Surgery and International Collaboration on Repair Discoveries, The University of British Columbia, Vancouver, BC, Canada
| | - C. James Lim
- Michael Cuccione Childhood Cancer Research Program, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Department of Pediatrics, The University of British Columbia, Vancouver, BC, Canada
| | - Aziz Ghahsary
- Burn & Wound Healing Research Group, Division of Plastic Surgery, Department of Surgery and International Collaboration on Repair Discoveries, The University of British Columbia, Vancouver, BC, Canada
| | - Gregor S. D. Reid
- Michael Cuccione Childhood Cancer Research Program, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Department of Pediatrics, The University of British Columbia, Vancouver, BC, Canada
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Epidermal Growth Factor Is Associated with Loss of Mucosae Sealing and Peri-Implant Mucositis: A Pilot Study. Healthcare (Basel) 2021; 9:healthcare9101277. [PMID: 34682957 PMCID: PMC8535843 DOI: 10.3390/healthcare9101277] [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: 08/03/2021] [Revised: 08/29/2021] [Accepted: 09/01/2021] [Indexed: 12/02/2022] Open
Abstract
This study aimed to evaluate the correlation between epidermal growth factor (EGF) and receptor (EGFR) levels in different clinical stages of dental implant rehabilitation and trace mucositis development’s biological profile. Thirty-six participants from the Specialization in Implant Dentistry, Universidade Federal Fluminense, Brazil, were included in the study and underwent sample collection: inside the alveolar socket, immediately before implant placement (Group 1, n = 10); at the peri-implant crevicular fluid (PICF) during reopening (Group 2, n = 10); PICF from healthy peri-implant in function (Group 3, n = 8); and PICF from mucositis sites (Group 4, n = 18). Quantitative polymerase chain reaction (PCR) evaluated EGF/EGFR gene expression using the SYBR Green Master Mix detection system. The results showed that EGF expression in the peri-implant crevicular fluid was statistically different. There was a higher EGF expression for group C (peri-implant health) (p = 0.04) than for the other groups. Regarding EGFR, there was no statistical difference among the groups (p = 0.56). It was concluded that low levels of EGF gene expression in the peri-implant crevicular fluid are related to the development of peri-implant mucositis and the absence of mucosae sealing. There was no correlation between EGFR gene expression with health or mucositis.
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Singh A, Maqsood Z, Iqubal MK, Ali J, Baboota S. Compendium of Conventional and Targeted Drug Delivery Formulation Used for the Treatment and Management of the Wound Healing. Curr Drug Deliv 2021; 19:192-211. [PMID: 34315364 DOI: 10.2174/1567201818666210727165916] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 06/21/2021] [Accepted: 07/01/2021] [Indexed: 11/22/2022]
Abstract
Wound healing is a complex and dynamic phenomenon that involves the restoration of normal physiology and functioning of injured tissue. The process of wound healing is primarily regulated by various cytokines, inflammatory mediators, and growth factors at the molecular level. Any intervention in the normal wound healing process leads to further tissue damage, which in turn leads to delayed wound healing. Several natural, synthetic drugs and their combinations were used to restored and accelerate the wound healing process. However, the conventional delivery carriers were not much effective, and thus, nowadays, nanocarriers are gaining much popularity since they are playing a pivotal role in drug delivery. Since nanocarriers have their own applicability and benefits (enhance the bioavailability, site-specific targeting) so, they can accelerate wound healing more efficiently. This review briefly discussed about the various events that take place during the wound healing process with emphasis on various natural, synthetic, and combination drug therapy used for accelerating wound healing and the role of nanotechnology-based approaches in chronic wound healing.
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Affiliation(s)
- Ajay Singh
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Zeba Maqsood
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Mohammad Kashif Iqubal
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Javed Ali
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Sanjula Baboota
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
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Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1. Sci Rep 2021; 11:13371. [PMID: 34183697 PMCID: PMC8238984 DOI: 10.1038/s41598-021-92650-w] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 06/11/2021] [Indexed: 12/14/2022] Open
Abstract
The severity of tissue injury in burn wounds from associated inflammatory and immune sequelae presents a significant clinical management challenge. Among various biophysical wound management approaches, low dose biophotonics treatments, termed Photobiomodulation (PBM) therapy, has gained recent attention. One of the PBM molecular mechanisms of PBM treatments involves photoactivation of latent TGF-β1 that is capable of promoting tissue healing and regeneration. This work examined the efficacy of PBM treatments in a full-thickness burn wound healing in C57BL/6 mice. We first optimized the PBM protocol by monitoring tissue surface temperature and histology. We noted this dynamic irradiance surface temperature-monitored PBM protocol improved burn wound healing in mice with elevated TGF-β signaling (phospho-Smad2) and reduced inflammation-associated gene expression. Next, we investigated the roles of individual cell types involved in burn wound healing following PBM treatments and noted discrete effects on epithelieum, fibroblasts, and macrophage functions. These responses appear to be mediated via both TGF-β dependent and independent signaling pathways. Finally, to investigate specific contributions of TGF-β1 signaling in these PBM-burn wound healing, we utilized a chimeric TGF-β1/β3 knock-in (TGF-β1Lβ3/Lβ3) mice. PBM treatments failed to activate the chimeric TGF-β1Lβ3/Lβ3 complex and failed to improve burn wound healing in these mice. These results suggest activation of endogenous latent TGF-β1 following PBM treatments plays a key role in burn wound healing. These mechanistic insights can improve the safety and efficacy of clinical translation of PBM treatments for tissue healing and regeneration.
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Szwedowski D, Szczepanek J, Paczesny Ł, Zabrzyński J, Gagat M, Mobasheri A, Jeka S. The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis. Int J Mol Sci 2021; 22:5492. [PMID: 34071037 PMCID: PMC8197096 DOI: 10.3390/ijms22115492] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/19/2021] [Accepted: 05/21/2021] [Indexed: 02/07/2023] Open
Abstract
Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.
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Affiliation(s)
- Dawid Szwedowski
- Orthopedic Arthroscopic Surgery International (O.A.S.I.) Bioresearch Foundation, Gobbi N.P.O., 20133 Milan, Italy
- Department of Orthopaedics and Trauma Surgery, Provincial Polyclinical Hospital, 87100 Torun, Poland
| | - Joanna Szczepanek
- Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87100 Torun, Poland;
| | - Łukasz Paczesny
- Orvit Clinic, Citomed Healthcare Center, 87100 Torun, Poland; (Ł.P.); (J.Z.)
| | - Jan Zabrzyński
- Orvit Clinic, Citomed Healthcare Center, 87100 Torun, Poland; (Ł.P.); (J.Z.)
| | - Maciej Gagat
- Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85067 Bydgoszcz, Poland;
| | - Ali Mobasheri
- Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, FI-90014 Oulu, Finland;
- Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Santariskiu 5, LT-08406 Vilnius, Lithuania
- Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
- Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Sławomir Jeka
- Department and Clinic of Rheumatology and Connective Tissue Diseases, University Hospital No. 2, Collegium Medicum UMK, 85168 Bydgoszcz, Poland;
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Raghunathan V, Park SA, Shah NM, Reilly CM, Teixeira L, Dubielzig R, Chang YR, Motta MJ, Schurr MJ, McAnulty JF, Isseroff RR, Abbott NL, Murphy CJ. Changing the Wound: Covalent Immobilization of the Epidermal Growth Factor. ACS Biomater Sci Eng 2021; 7:2649-2660. [PMID: 34018720 DOI: 10.1021/acsbiomaterials.1c00192] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Re-epithelialization of wounds is a critical element of wound closure. Growth factors have been used in combination with conventional wound management to promote closure, but the method of delivery has been limited to the topical application of ointment formulations. Cytoactive factors delivered in this way have short resident times in wounds and have met with limited success. Here, we demonstrate that methods used to covalently immobilize proteins on synthetic materials can be extended to immobilize cytoactive factors such as the epidermal growth factor (EGF) onto the wound beds of genetically diabetic mice that exhibit impaired healing. Full-thickness splinted excisional wounds were created in diabetic (db/db) mice with a well-defined silicone splint to limit wound contracture. Wound surfaces were treated with a reducing agent to expose sulfhydryl groups and subsequently treated with EGF modified with a heterobifunctional crosslinker. This allowed for the covalent immobilization of the EGF to the wound surface. The conjugation chemistry was validated in vitro and in vivo. In a separate group of mice, wounds were topically treated twice daily with soluble EGF. The mice were evaluated over 11 days for wound closure. This covalent immobilization strategy resulted in EGF being retained on the wound surface for 2 days and significantly increased epithelial wound closure by 20% compared to wounds treated with topical EGF or topical vehicle. Covalent immobilization was not only therapeutically effective but also delivered a markedly reduced load of growth factor to the wound surface compared to topical application (when only 180 ng of EGF was immobilized onto the wound surface in comparison with 7200 ng of topically applied EGF over a period of 11 days). No adverse effects were observed in treated wounds. Results obtained provide proof of concept for the effectiveness of covalent immobilization in the treatment of dysregulated wounds. The covalent immobilization of cytoactive factors represents a potentially transformative approach to the management of difficult chronic wounds.
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Affiliation(s)
- VijayKrishna Raghunathan
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States.,Department of Basic Sciences, College of Optometry, University of Houston, 4901 Calhoun Rd, Houston, Texas 77204, United States.,Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, Texas 77204, United States
| | - Shin Ae Park
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States.,Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, 625 Harrison Street, West Lafayette, Indiana 47907, United States
| | - Nihar M Shah
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States.,Medtronic Diabetes, 18000 Devonshire Street, Northridge, California 91325-1219, United States
| | - Christopher M Reilly
- Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States
| | - Leandro Teixeira
- Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States
| | - Richard Dubielzig
- Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States
| | - Yow-Ren Chang
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States
| | - Monica J Motta
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States
| | - Michael J Schurr
- Divison of General Surgery, Mountain Area Health Education Center, 509 Biltmore Avenue, Asheville, North Carolina 28803, United States
| | - Jonathan F McAnulty
- Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, Wisconsin 53706, United States
| | - R Rivkah Isseroff
- Department of Dermatology, UC Davis School of Medicine, University of California Davis, Sacramento, California 95817, United States
| | - Nicholas L Abbott
- Smith School of Chemical and Biomolecular Engineering, Cornell University, 1 Hoy Plaza, Ithaca, New York 14853 United States
| | - Christopher J Murphy
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States.,Department of Ophthalmology & Vision Science, School of Medicine, University of California Davis, One Shields Avenue, Davis, California 95817, United States
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Ebrahimzade M, Mirdoraghi M, Alikarami A, Heidari S, Rastegar T, Partoazar AR, Takzaree N. Comparison of the Effect of Adipocyte-derived Stem Cells and Curcumin Nanoliposomes with Phenytoin on Open Cutaneous Wound Healing in Rats. Endocr Metab Immune Disord Drug Targets 2020; 21:866-877. [PMID: 32811405 DOI: 10.2174/1871530320999200817172200] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 06/16/2020] [Accepted: 07/01/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Reducing the healing time of wounds can decrease the patient's immobility time and their medical costs, leading a faster return of the patients to daily work. OBJECTIVE The aim of the present study is to compare the effect of adipose-derived stem cells and curcumin- containing liposomal nanoparticles with phenytoin on wound healing. METHODS After anesthesia of the rats, open skin ulcers were made by a bistoury blade. Subsequently, stem cells were removed from the adipose tissue of the upper border of the epididymis. The originality of stem cells was then confirmed by the flow cytometry. The fusion method was used to prepare the liposome; and also, nanoliposomal particles were confirmed by using the DLS microscope. The percentage of recovery and the cell count was measured with IMAGEJ. The expression of genes was assessed by PCR. The number of fibroblasts was counted by immunohistochemistry techniques. The amount of collagen was determined by Tri-chromosome staining, and the number of capillaries was enumerated by H & E staining. RESULTS The expression of the TGF-β1 gene, vascular number, wound healing rate and the number of fibroblasts increased significantly in adipose tissue-derived stem cells and curcumin nanoliposome groups (p<0.05); the wound surface was also decreased significantly (p<0.05). CONCLUSION Based on the results of our research, adipose tissue-derived stem cells and curcumin nanoliposomes can heal wounds efficiently.
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Affiliation(s)
| | - Mohammad Mirdoraghi
- Department of Radiology and Radiotherapy, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ameneh Alikarami
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sahar Heidari
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Tayebeh Rastegar
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali R Partoazar
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasrin Takzaree
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Huddleston HP, Cohn MR, Haunschild ED, Wong SE, Farr J, Yanke AB. Amniotic Product Treatments: Clinical and Basic Science Evidence. Curr Rev Musculoskelet Med 2020; 13:148-154. [PMID: 32076938 PMCID: PMC7174465 DOI: 10.1007/s12178-020-09614-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Orthobiologics, including amniotic products, have been gaining interest in the past decade for the treatment of various orthopedic conditions including osteoarthritis. However, the use of biologics is varied and is currently available with minimal oversight or regulation. This review will assess the current state of research that utilizes amniotic products both in vitro and in vivo. RECENT FINDINGS Amniotic tissue derivatives have been shown to have positive effects in animal models for a variety of conditions. Clinical trials are limited with mixed outcomes, yet some recent studies suggest the rationale for continued investigation. While amniotic products appear promising in numerous animal studies, human clinical trials are still lacking. Future studies are needed to assess whether amniotic products have a role in the treatment of osteoarthritis and other orthopedic pathologies.
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Affiliation(s)
- Hailey P Huddleston
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, 1611 W. Harrison St, Suite 300, Chicago, IL, 60612, USA
| | - Matthew R Cohn
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, 1611 W. Harrison St, Suite 300, Chicago, IL, 60612, USA
| | - Eric D Haunschild
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, 1611 W. Harrison St, Suite 300, Chicago, IL, 60612, USA
| | - Stephanie E Wong
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, 1611 W. Harrison St, Suite 300, Chicago, IL, 60612, USA
| | - Jack Farr
- Knee Preservation and Cartilage Restoration Center, OrthoIndy, Indianapolis, IN, USA
| | - Adam B Yanke
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, 1611 W. Harrison St, Suite 300, Chicago, IL, 60612, USA.
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Regenerative Rehabilitative Medicine for Joints and Muscles. CURRENT PHYSICAL MEDICINE AND REHABILITATION REPORTS 2020. [DOI: 10.1007/s40141-019-00254-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Scarneo SA, Eibschutz LS, Bendele PJ, Yang KW, Totzke J, Hughes P, Fox DA, Haystead TAJ. Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice. Arthritis Res Ther 2019; 21:292. [PMID: 31847895 PMCID: PMC6918687 DOI: 10.1186/s13075-019-2073-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 11/28/2019] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES To examine the ability of takinib, a selective transforming growth factor beta-activated kinase 1 (TAK1) inhibitor, to reduce the severity of murine type II collagen-induced arthritis (CIA), and to affect function of synovial cells. METHODS Following the induction of CIA, mice were treated daily with takinib (50 mg/kg) and clinical scores assessed. Thirty-six days post-CIA induction, histology was performed on various joints of treated and vehicle-treated animals. Inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation were quantified. Furthermore, pharmacokinetics of takinib were evaluated by LC-MS in various tissues. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells were cultured with 10 μM takinib and cytokine secretion analyzed by cytokine/chemokine proteome array. Cytotoxicity of takinib for RA-FLS was measured with 24 to 48 h cultures in the presence or absence of tumor necrosis factor (TNF). RESULTS Here, we show takinib's ability to reduce the clinical score in the CIA mouse model of rheumatoid arthritis (RA) (p < 0.001). TAK1 inhibition reduced inflammation (p < 0.01), cartilage damage (p < 0.01), pannus, bone resorption, and periosteal bone formation and periosteal bone width in all joints of treated mice compared to vehicle treated. Significant reduction of inflammation (p < 0.004) and cartilage damage (p < 0.004) were observed in the knees of diseased treated animals, with moderate reduction seen in the forepaws and hind paws. Furthermore, the pharmacokinetics of takinib show rapid plasma clearance (t½ = 21 min). In stimulated RA-FLS cells, takinib reduced GROα, G-CSF, and ICAM-1 pro-inflammatory cytokine signaling. CONCLUSION Our findings support the hypothesis that TAK1 targeted therapy represents a novel therapeutic axis to treat RA and other inflammatory diseases.
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Affiliation(s)
- Scott A Scarneo
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, LSRC C112, 308 Research Drive, Durham, NC, 27710, USA
| | - Liesl S Eibschutz
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, LSRC C112, 308 Research Drive, Durham, NC, 27710, USA
| | - Phillip J Bendele
- Bolder BioPATH, Inc., 5541 Central Ave., Suite 160, Boulder, CO, 80301, USA
| | - Kelly W Yang
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, LSRC C112, 308 Research Drive, Durham, NC, 27710, USA
| | - Juliane Totzke
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, LSRC C112, 308 Research Drive, Durham, NC, 27710, USA
| | - Philip Hughes
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, LSRC C112, 308 Research Drive, Durham, NC, 27710, USA
| | - David A Fox
- Division of Rheumatology and Clinical Autoimmunity Center of Excellence, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Timothy A J Haystead
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, LSRC C112, 308 Research Drive, Durham, NC, 27710, USA.
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Yan Y, Jiang J, Zhang M, Chen Y, Wang X, Huang M, Zhang L. Effect of iPSCs-derived keratinocytes on healing of full-thickness skin wounds in mice. Exp Cell Res 2019; 385:111627. [DOI: 10.1016/j.yexcr.2019.111627] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Revised: 08/29/2019] [Accepted: 09/17/2019] [Indexed: 12/21/2022]
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Triamcinolone Acetonide Suppresses Keloid Formation Through Enhancing Apoptosis in a Nude Mouse Model. Ann Plast Surg 2019; 83:S50-S54. [PMID: 31513066 DOI: 10.1097/sap.0000000000002090] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Current understanding of steroid treatments for keloids is in regards to modulation of inflammation, proliferation, and apoptosis, with no in vivo study on the latter. Using a nude mouse model, we investigated whether triamcinolone acetonide (TA) injections induce keloids regression through enhancing apoptosis. MATERIALS AND METHODS Thirty-six keloid specimens (1 × 1 cm) were harvested from 6 patients and separated into sets of 2 from the same patient: no treatment and intralesional TA injection (0.4 mg/mL/kg) at 8 weeks of postimplantation. One set was implanted in each of 18 randomly selected nude mice, which were separated into 3 groups based on time of keloid harvesting after treatment: group A, 2 weeks; group B, 8 weeks; and group C, 14 weeks. Each group had 1 set of specimen from each patient. Histological staining was performed with hematoxylin and eosin stain. Immunohistochemistry staining was performed for human-prolyl 4-hydroxylase (hPH4) and caspase 3 protein, along with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS All keloid specimens survived, with no noted overgrowth. Hematoxylin and eosin staining revealed dense extracellular matrix and viable fibroblasts, and hPH4 immunohistochemistry revealed strong expression, demonstrating keloid viability. Caspase 3 protein and TUNEL expressions were significantly increased in the treatment versus control groups, demonstrating that TA injections induced apoptosis. CONCLUSIONS Triamcinolone acetonide intralesional injections significantly increased apoptosis in keloids, represented by increased caspase 3 protein and TUNEL expressions, supporting that steroids suppress keloids in part owing to enhancement of apoptosis.
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Masieri L, Sessa F, Mari A, Campi R, Cito G, Verrienti P, Nozzoli C, Saccardi R, Sforza S, Di Maida F, Grosso AA, Carini M, Minervini A. Intravesical application of platelet-rich plasma in patients with persistent haemorrhagic cystitis after hematopoietic stem cell transplantation: a single-centre preliminary experience. Int Urol Nephrol 2019; 51:1715-1720. [DOI: 10.1007/s11255-019-02223-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 07/01/2019] [Indexed: 10/26/2022]
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Urits I, Viswanath O, Galasso AC, Sottosani ER, Mahan KM, Aiudi CM, Kaye AD, Orhurhu VJ. Platelet-Rich Plasma for the Treatment of Low Back Pain: a Comprehensive Review. Curr Pain Headache Rep 2019; 23:52. [PMID: 31270622 DOI: 10.1007/s11916-019-0797-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Back pain is a growing problem worldwide, incurring enormous economic costs and disability. Current treatment modalities often provide adequate relief but fail to address underlying conditions. Regenerative cellular modalities aim to restore anatomical function in degenerative conditions which may cause low back pain. Platelet-rich plasma (PRP) consists of an increased concentration of autologous platelets suspended in a small amount of plasma. PRP can be administered via injection or topically and is prepared using various techniques. RECENT FINDINGS While a unifying mechanism of action is not well understood, biochemical and cellular changes involved in inflammation and mechanical structure have been detected in both in vitro and in vivo studies. At a higher level, PRP injection research utilizing animal models and patient data have provided insights into pain relief, chondroprotection, and factors that impact the therapy's efficacy. Recently, a small number of studies have promoted PRP injection as a relatively safe means of treating patients with degenerative disc disease who have failed other means of managing their lower back pain. PRP injections for sacroiliac joint-related pain are not an accepted or common treatment modality; the evidence for their efficacy remains to be seen outside of small RCTs and case reports. A small number of prospective trials have suggested there may be some benefit to using PRP injection in the treatment of pain or functional decline caused by facet joint arthropathy. These commonly used modalities require further study to improve quality of evidence and to investigate the safety and efficacy of PRP injections for various common causes of chronic low back.
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Affiliation(s)
- Ivan Urits
- Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA.
| | - Omar Viswanath
- Valley Anesthesiology and Pain Consultants, Phoenix, AZ, USA.,Department of Anesthesiology, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA.,Department of Anesthesiology, Creighton University School of Medicine, Omaha, NE, USA
| | | | | | | | - Christopher M Aiudi
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Alan D Kaye
- Department of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Vwaire J Orhurhu
- Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
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Eliezer M, Sculean A, Miron RJ, Nemcovsky C, Weinberg E, Weinreb M, Zoabi H, Bosshardt DD, Fujioka‐Kobayashi M, Moses O. Hyaluronic acid slows down collagen membrane degradation in uncontrolled diabetic rats. J Periodontal Res 2019; 54:644-652. [PMID: 31190426 DOI: 10.1111/jre.12665] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 03/13/2019] [Accepted: 04/12/2019] [Indexed: 11/30/2022]
Affiliation(s)
- Meizi Eliezer
- Department of Periodontology School of Dental Medicine University of Bern Bern Switzerland
| | - Anton Sculean
- Department of Periodontology School of Dental Medicine University of Bern Bern Switzerland
| | - Richard J. Miron
- Department of Periodontology School of Dental Medicine University of Bern Bern Switzerland
| | - Carlos Nemcovsky
- Department of Periodontology and Dental Implantology The Maurice and Gabriela Goldschleger School of Dental Medicine Tel Aviv University Tel Aviv Israel
| | - Evegeny Weinberg
- Department of Periodontology and Dental Implantology The Maurice and Gabriela Goldschleger School of Dental Medicine Tel Aviv University Tel Aviv Israel
| | - Miron Weinreb
- Department of Oral Biology The Maurice and Gabriela Goldschleger School of Dental Medicine Tel Aviv University Tel Aviv Israel
| | - Hasan Zoabi
- Department of Oral Biology The Maurice and Gabriela Goldschleger School of Dental Medicine Tel Aviv University Tel Aviv Israel
| | - Dieter D. Bosshardt
- Department of Periodontology School of Dental Medicine University of Bern Bern Switzerland
- Robert K. Schenk Laboratory of Oral Histology School of Dental Medicine University of Bern Bern Switzerland
| | - Masako Fujioka‐Kobayashi
- Department of Cranio‐Maxillofacial Surgery, Inselspital Bern University Hospital University of Bern Bern Switzerland
| | - Ofer Moses
- Department of Periodontology and Dental Implantology The Maurice and Gabriela Goldschleger School of Dental Medicine Tel Aviv University Tel Aviv Israel
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Mapping Tyrosine Kinase Receptor Dimerization to Receptor Expression and Ligand Affinities. Processes (Basel) 2019. [DOI: 10.3390/pr7050288] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Tyrosine kinase receptor (RTK) ligation and dimerization is a key mechanism for translating external cell stimuli into internal signaling events. This process is critical to several key cell and physiological processes, such as in angiogenesis and embryogenesis, among others. While modulating RTK activation is a promising therapeutic target, RTK signaling axes have been shown to involve complicated interactions between ligands and receptors both within and across different protein families. In angiogenesis, for example, several signaling protein families, including vascular endothelial growth factors and platelet-derived growth factors, exhibit significant cross-family interactions that can influence pathway activation. Computational approaches can provide key insight to detangle these signaling pathways but have been limited by the sparse knowledge of these cross-family interactions. Here, we present a framework for studying known and potential non-canonical interactions. We constructed generalized models of RTK ligation and dimerization for systems of two, three and four receptor types and different degrees of cross-family ligation. Across each model, we developed parameter-space maps that fully determine relative pathway activation for any set of ligand-receptor binding constants, ligand concentrations and receptor concentrations. Therefore, our generalized models serve as a powerful reference tool for predicting not only known ligand: Receptor axes but also how unknown interactions could alter signaling dimerization patterns. Accordingly, it will drive the exploration of cross-family interactions and help guide therapeutic developments across processes like cancer and cardiovascular diseases, which depend on RTK-mediated signaling.
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Mogaki R, Okuro K, Ueki R, Sando S, Aida T. Molecular Glue that Spatiotemporally Turns on Protein–Protein Interactions. J Am Chem Soc 2019; 141:8035-8040. [DOI: 10.1021/jacs.9b02427] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Rina Mogaki
- Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Kou Okuro
- Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Ryosuke Ueki
- Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Shinsuke Sando
- Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Takuzo Aida
- Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
- Riken Center for Emergent Matter Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
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Lv X, Feng R, Zhai J. A combination of mupirocin and acidic fibroblast growth factor for nipple fissure and nipple pain in breastfeeding women: protocol for a randomised, double-blind, controlled trial. BMJ Open 2019; 9:e025526. [PMID: 30918032 PMCID: PMC6475339 DOI: 10.1136/bmjopen-2018-025526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 02/17/2019] [Accepted: 02/21/2019] [Indexed: 01/12/2023] Open
Abstract
INTRODUCTION Nipple fissure and nipple pain are common complaints among breastfeeding mothers. Studies found that mupirocin was effective in preventing and treating infections of damaged nipple and nipple pain. Acidic fibroblast growth factor (aFGF) plays an important role in wound healing. However, current evidence on the efficacy and safety of mupirocin plus aFGF for nipple fissure and nipple pain in breastfeeding women is inconclusive due to the lack of well-designed randomised controlled trials on this topic. The purpose of this study is to test the hypothesis that mupirocin plus aFGF is more effective than mupirocin alone for nipple fissure and nipple pain in breastfeeding women. METHODS AND ANALYSIS This study is a randomised, double-blind, single-centre, parallel-group clinical trial. A total of 120 breastfeeding women with nipple fissure and nipple pain will be randomly assigned to either mupirocin plus aFGF group or mupirocin plus placebo group according to a computer-generated random allocation sequence. The treatment period lasts 14 days. The primary outcome is nipple pain intensity measured by the Visual Analogue Scale on day 14 during the treatment period. Secondary outcome measures include time to complete nipple pain relief, changes in the Nipple Trauma Score, time to complete healing of nipple trauma, quality of life measured by the Maternal Postpartum Quality of Life (MAPP-QOL) Questionnaire, the frequency of breast feeding, the rate of breastfeeding discontinuation, weight change in infants and adverse events. ETHICS AND DISSEMINATION The study has gained approval from the Ethics Review Committee of Tianjin Central Hospital of Gynaecology Obstetrics on 22 January 2018 (approval no. 2018KY001). We plan to publish our research findings in a peer-reviewed academic journal and disseminate these findings in international conferences. This study has been registered with the Chinese Clinical Trial Registry. TRIAL REGISTRATION NUMBER ChiCTR1800017248.
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Affiliation(s)
- Xiaofang Lv
- Galactophore Department, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China
| | - Rui Feng
- Galactophore Department, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China
| | - Jingbo Zhai
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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