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Kong S, Yang Y, Gao Y, Hu F, Yang S, Gao Z, Zhang K, Bai W, Cheng J, Hu X, Guo Q, Gong X, Ao Y, Shi W. Biodegradable Cryo-Self-Assembled Silk Fibroin Sponge for Enzyme-Responsive Exosome Delivery to Enhance Tendon Regeneration. ACS APPLIED BIO MATERIALS 2025; 8:3697-3707. [PMID: 40244687 DOI: 10.1021/acsabm.4c01429] [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: 04/19/2025]
Abstract
The utilization of biological therapeutic agents in the treatment of tendon injuries represents a promising avenue, with particular attention drawn to adipose mesenchymal stem-cell-derived exosomes (ADSCs-exos) owing to their pivotal role in regenerative medicine. Identifying a therapeutic strategy to prolong exosome retention at the injury site for effective tendon repair remains challenging. In this study, we explored the potential of ADSC-exosomes in vitro, demonstrating their ability to promote the behavior of tendon stem/progenitor cells (TSPCs). Additionally, we designed a fibroin (SF) sponge as a biodegradable platform for enzyme-responsive exosome delivery. Subsequently, we used biodegradable SF sponges to deliver ADSC exosomes into the patellar tendon defect in rats. The results showed that, in vivo, exosomes were gradually released from the SF sponges, remained in the defect area for an extended period, and exerted functional benefits locally. These findings were supported by the upregulation of tendon-associated protein expression and improved mechanical properties observed in the in vivo specimens. In summary, we substantiated the advantageous role of ADSCs-exos in facilitating tendon regeneration. Moreover, the utilization of a SF-exos sponge delivery system emerged as an efficacious local treatment strategy for exosome delivery. These findings hold promise for the future application of exosomes in innovative therapies tailored to address tendon injuries.
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Affiliation(s)
- Simin Kong
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Yuping Yang
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Yitian Gao
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Fengyi Hu
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Shuai Yang
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Zeyuan Gao
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Keying Zhang
- Peking University Health Science Center, Beijing 100191, China
| | - Wenbin Bai
- Peking University Health Science Center, Beijing 100191, China
| | - Jin Cheng
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Xiaoqing Hu
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Qinwei Guo
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Xi Gong
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Yingfang Ao
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
| | - Weili Shi
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, China
- Beijing Key Laboratory of Sports Injuries, Beijing 100191, China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing 100191, China
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Yuan Z, Yao Z, Mao X, Gao X, Wu S, Mao H. Epigenetic mechanisms in stem cell therapies for achilles tendinopathy. Front Cell Dev Biol 2025; 13:1516250. [PMID: 40181824 PMCID: PMC11965899 DOI: 10.3389/fcell.2025.1516250] [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: 10/24/2024] [Accepted: 02/20/2025] [Indexed: 04/05/2025] Open
Abstract
Achilles tendinopathy (AT) is a chronic degenerative tendinopathy that affects people's daily lives. Multiple clinical studies have found that current conservative treatments fail to promote quality tendon healing. Recent studies have found that stem cell therapy can target pathophysiological changes in the tendon by replenishing tendon-derived cells, promoting extracellular matrix (ECM) remodeling, and modulating the inflammatory response to improve the microenvironment of Achilles tendon regeneration. And epigenetic modifications play an important role in stem cell fate determination and function. In this review, we provided a brief overview of the biological properties of relevant stem cells. The influence of epigenetic modifications on stem cell proliferation, differentiation, and immune regulatory function in the treatment of AT was also explored. We focused on gene regulatory mechanisms controlled by DNA methylation, histones and non-coding RNAs including microRNAs, circRNAs and long non-coding RNAs. We also discuss the current challenges faced by stem cell therapies in treating AT and their potential solutions. Further research in this area will provide a more comprehensive epigenetic explanation for stem cell therapy for AT, leading to the development of stable, safe and effective stem cell therapies.
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Affiliation(s)
| | | | | | | | | | - Haijiao Mao
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
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Rahman E, Carruthers JDA, Rao P, Abu-Farsakh HN, Garcia PE, Ioannidis S, Sayed K, Philipp-Dormston WG, Mosahebi A, Webb WR. Regenerative Aesthetics: A Genuine Frontier or Just a Facet of Regenerative Medicine: A Systematic Review. Aesthetic Plast Surg 2025; 49:341-355. [PMID: 39198280 DOI: 10.1007/s00266-024-04287-5] [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: 05/11/2024] [Accepted: 07/24/2024] [Indexed: 09/01/2024]
Abstract
BACKGROUND Regenerative aesthetics claims to enhance cosmetic outcomes through advanced biological interventions like Stem cell and Exosome therapy, Polydeoxyribonucleotide (PDRN), Photobiomodulation, bioactive peptides and treatment for cellular senescence yet lacks substantial scientific and regulatory validation. OBJECTIVE To evaluate the scientific and clinical foundations of regenerative medicine techniques in non-surgical aesthetics and assess the legitimacy of regenerative aesthetics as a medical specialty. METHODS A systematic review was conducted according to PRISMA guidelines, searching databases including PubMed, Scopus, and Web of Science for studies published in the last ten years. We included 19 studies, comprising 14 randomized controlled trials (RCTs) and 5 prospective studies, focusing on interventions that purportedly use regenerative medicine principles in aesthetic applications. RESULTS The review highlights a prevalent gap in molecular and clinical evidence supporting the efficacy and safety of regenerative aesthetics. Despite the robust design of the included RCTs and prospective studies, there remains a significant lack of consistent, high-quality evidence proving the effectiveness of these interventions. Issues such as inadequate reporting, unclear molecular mechanisms, and absence of long-term safety data were common. CONCLUSION The field of regenerative aesthetics lacks the necessary scientific rigour and regulatory compliance to be recognized as a legitimate medical specialty. This review underscores the need for stringent scientific validation and regulatory oversight to ensure patient safety and treatment efficacy before these techniques can be recommended for clinical use. LEVEL OF EVIDENCE II This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Eqram Rahman
- Research and Innovation Hub, Innovation Aesthetics, London, WC2H 9JQ, UK
| | - Jean D A Carruthers
- Department of Ophthalmology, University of British Columbia, Vancouver, BC, Canada
| | - Parinitha Rao
- The Skin Address, Aesthetic Dermatology Practice, Bangalore, India
| | | | | | | | - Karim Sayed
- Nomi Oslo, Oslo, Norway
- University of South-Eastern Norway, Drammen, Norway
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Roets B, Abrahamse H, Crous A. The Application of Photobiomodulation on Mesenchymal Stem Cells and its Potential Use for Tenocyte Differentiation. Curr Stem Cell Res Ther 2025; 20:232-245. [PMID: 38847377 DOI: 10.2174/011574888x295488240319111911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 02/23/2024] [Accepted: 03/02/2024] [Indexed: 05/13/2025]
Abstract
Tendinopathy is a prevalent and debilitating musculoskeletal disorder. Uncertainty remains regarding its pathophysiology, but it is believed to be a combination of inflammation, damage, degenerative changes, and unsuccessful repair mechanisms. Cell-based therapy is an emerging regenerative medicine modality that uses mesenchymal stem cells (MSCs), their progeny or exosomes to promote tendon healing and regeneration. It is based on the fact that MSCs can be differentiated into tenocytes, the major cell type within tendons, and facilitate tendon repair. Photobiomodulation (PBM) is a non-invasive and potentially promising therapeutic technique that utilizes low-level light to alter intracellular processes and promote tissue healing and regeneration. Recent studies have examined the potential for PBM to improve MSC therapy use in tendinopathy by promoting viability, proliferation, and differentiation. As well as enhance tendon regeneration. This review focuses on Photobiomodulation and MSC therapy applications in regenerative medicine and their potential for tendon tissue engineering.
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Affiliation(s)
- Brendon Roets
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa
| | - Anine Crous
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa
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Fernandez‐Yague MA, Palma M, Tofail SAM, Duffy M, Quinlan LR, Dalby MJ, Pandit A, Biggs MJ. A Tympanic Piezo-Bioreactor Modulates Ion Channel-Associated Mechanosignaling to Stabilize Phenotype and Promote Tenogenesis in Human Tendon-Derived Cells. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2405711. [PMID: 39439240 PMCID: PMC11615817 DOI: 10.1002/advs.202405711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 08/22/2024] [Indexed: 10/25/2024]
Abstract
Preserving the function of human tendon-derived cells (hTDCs) during cell expansion is a significant challenge in regenerative medicine. In this study, a non-genetic approach is introduced to control the differentiation of hTDCs using a newly developed tympanic bioreactor. The system mimics the functionality of the human tympanic membrane, employing a piezoelectrically tuned acoustic diaphragm made of polyvinylidene fluoride-co-trifluoroethylene and boron nitride nanotubes. The diaphragm is vibrationally actuated to deliver targeted electromechanical stimulation to hTDCs. The results demonstrate that the system effectively maintains the tendon-specific phenotype of hTDCs, even under conditions that typically induce nonspecific differentiation, such as osteogenesis. This stabilization is achieved by modulating integrin-mediated mechanosignaling via ion channel-regulated calcium activity, potentially by TREK-1 and PIEZO1, yet targeted studies are required for confirmation. Finally, the system sustains the activation of key differentiation pathways (bone morphogenetic protein, BMP) while downregulating osteogenesis-associated (mitogen-ctivated protein kinase, MAPK and wingless integrated, WNT) pathways and upregulating Focal Adhesion Kinase (FAK) signaling. This approach offers a finely tunable, dose-dependent control over hTDC differentiation, presenting significant potential for non-genetic approaches in cell therapy, tendon tissue engineering, and the regeneration of other mechanosensitive tissues.
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Affiliation(s)
- Marc A. Fernandez‐Yague
- CÚRAM SFI Research Centre for Medical DevicesUniversity of GalwayGalwayH91W2TYIreland
- Department of ChemistryQueen Mary University of LondonMile End RoadLondonE1 4NSUnited Kingdom
| | - Matteo Palma
- Department of ChemistryQueen Mary University of LondonMile End RoadLondonE1 4NSUnited Kingdom
| | - Syed A. M. Tofail
- Department of Physics and Bernal InstituteUniversity of LimerickLimerickV94 T9PXIreland
| | - Maeve Duffy
- CÚRAM SFI Research Centre for Medical DevicesUniversity of GalwayGalwayH91W2TYIreland
| | - Leo R. Quinlan
- CÚRAM SFI Research Centre for Medical DevicesUniversity of GalwayGalwayH91W2TYIreland
| | - Mathew J. Dalby
- Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research CentreUniversity of Glasgow11 Chapel LaneGlasgowG11 6EWUnited Kingdom
| | - Abhay Pandit
- CÚRAM SFI Research Centre for Medical DevicesUniversity of GalwayGalwayH91W2TYIreland
| | - Manus J. Biggs
- CÚRAM SFI Research Centre for Medical DevicesUniversity of GalwayGalwayH91W2TYIreland
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Morya VK, Shahid H, Lang J, Kwak MK, Park SH, Noh KC. Advancements in Therapeutic Approaches for Degenerative Tendinopathy: Evaluating Efficacy and Challenges. Int J Mol Sci 2024; 25:11846. [PMID: 39519397 PMCID: PMC11545934 DOI: 10.3390/ijms252111846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/31/2024] [Accepted: 11/02/2024] [Indexed: 11/16/2024] Open
Abstract
Degenerative tendinopathy results from the accumulation of minor injuries following unsuccessful tendon repair during acute tendon injuries. The process of tendon repair is prolonged and varies between individuals, making it susceptible to reinjury. Moreover, treating chronic tendinopathy often requires expensive and extensive rehabilitation, along with a variety of combined therapies to facilitate recovery. This condition significantly affects the quality of life of affected individuals, underscoring the urgent need for more efficient and cost-effective treatment options. Although traditional treatments have improved significantly and are being used as substitutes for surgical interventions, the findings have been inconsistent and conflicting. This review aims to clarify these issues by exploring the strengths and limitations of current treatments as well as recent innovations in managing various forms of degenerative tendinopathy.
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Affiliation(s)
- Vivek Kumar Morya
- Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si 18450, Republic of Korea; (V.K.M.); (J.L.)
- School of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Hamzah Shahid
- Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si 18450, Republic of Korea; (V.K.M.); (J.L.)
- School of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Jun Lang
- Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si 18450, Republic of Korea; (V.K.M.); (J.L.)
- School of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Mi Kyung Kwak
- Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si 18450, Republic of Korea; (V.K.M.); (J.L.)
- School of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Sin-Hye Park
- Department of Food Science & Nutrition, Hallym University, Chuncheon 24252, Republic of Korea
| | - Kyu-Cheol Noh
- School of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
- Hallym University Sacred Heart Hospital, Anyang-si 14068, Republic of Korea
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Ruan WJ, Xu SS, Xu DH, Li ZP. Orthopedic revolution: The emerging role of nanotechnology. World J Orthop 2024; 15:932-938. [PMID: 39473517 PMCID: PMC11514548 DOI: 10.5312/wjo.v15.i10.932] [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: 02/21/2024] [Revised: 08/24/2024] [Accepted: 09/11/2024] [Indexed: 10/11/2024] Open
Abstract
This review summarizes the latest progress in orthopedic nanotechnology, explores innovative applications of nanofibers in tendon repair, and evaluates the potential of selenium and cerium oxide nanoparticles in osteoarthritis and osteoblast differentiation. This review also describes the emerging applications of injectable hydrogels in cartilage engineering, emphasizing the critical role of interdisciplinary research and highlighting the challenges and future prospects of integrating nanotechnology into orthopedic clinical practice. This comprehensive approach provides a holistic perspective on the transformative impact of nanotechnology in orthopedics, offering valuable insights for future research and clinical applications.
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Affiliation(s)
- Wen-Jie Ruan
- Department of Sports Medicine, Zhejiang Provincial People's Hospital (The Affiliated People's Hospital), Hangzhou 310000, Zhejiang Province, China
| | - Si-Si Xu
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Dong-Hui Xu
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Zhi-Peng Li
- The Second Department of Orthopedics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, Henan Province, China
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He W, Jiang C, Zhou P, Hu X, Gu X, Zhang S. Role of tendon-derived stem cells in tendon and ligament repair: focus on tissue engineer. Front Bioeng Biotechnol 2024; 12:1357696. [PMID: 39175617 PMCID: PMC11338810 DOI: 10.3389/fbioe.2024.1357696] [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: 12/18/2023] [Accepted: 07/29/2024] [Indexed: 08/24/2024] Open
Abstract
This review offered a comprehensive analysis of tendon and ligament injuries, emphasizing the crucial role of tendon-derived stem cells (TDSCs) in tissue engineering as a potential solution for these challenging medical conditions. Tendon and ligament injuries, prevalent among athletes, the elderly, and laborers, often result in long-term disability and reduced quality of life due to the poor intrinsic healing capacity of these avascular structures. The formation of biomechanically inferior scar tissue and a high rate of reinjury underscore the need for innovative approaches to enhance and guide the regenerative process. This review delved into the complexities of tendon and ligament structure and function, types of injuries and their impacts, and the limitations of the natural repair process. It particularly focused on the role of TDSCs within the context of tissue engineering. TDSCs, with their ability to differentiate into tenocytes, are explored in various applications, including biocompatible scaffolds for cell tracking, co-culture systems to optimize tendon-bone healing, and graft healing techniques. The review also addressed the challenges of immunoreactivity post-transplantation, the importance of pre-treating TDSCs, and the potential of hydrogels and decellularized matrices in supporting tendon regeneration. It concluded by highlighting the essential roles of mechanical and molecular stimuli in TDSC differentiation and the current challenges in the field, paving the way for future research directions.
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Affiliation(s)
- Wei He
- Shaoxing People’s Hospital, Shaoxing, Zhejiang, China
| | - Chao Jiang
- Shaoxing People’s Hospital, Shaoxing, Zhejiang, China
| | - Ping Zhou
- Shaoxing People’s Hospital, Shaoxing, Zhejiang, China
| | - Xujun Hu
- Shaoxing People’s Hospital, Shaoxing, Zhejiang, China
| | - XiaoPeng Gu
- Department of Clinical Medicine, Health Science Center, Ningbo University, Ningbo, Zhejiang, China
- Department of Orthopedics, Zhoushan Guhechuan Hospital, Zhoushan, Zhejiang, China
| | - SongOu Zhang
- Shaoxing People’s Hospital, Shaoxing, Zhejiang, China
- Department of Clinical Medicine, Health Science Center, Ningbo University, Ningbo, Zhejiang, China
- Department of Orthopedics, Zhoushan Guhechuan Hospital, Zhoushan, Zhejiang, China
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Shahid H, Morya VK, Oh JU, Kim JH, Noh KC. Hypoxia-Inducible Factor and Oxidative Stress in Tendon Degeneration: A Molecular Perspective. Antioxidants (Basel) 2024; 13:86. [PMID: 38247510 PMCID: PMC10812560 DOI: 10.3390/antiox13010086] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 01/23/2024] Open
Abstract
Tendinopathy is a debilitating condition marked by degenerative changes in the tendons. Its complex pathophysiology involves intrinsic, extrinsic, and physiological factors. While its intrinsic and extrinsic factors have been extensively studied, the role of physiological factors, such as hypoxia and oxidative stress, remains largely unexplored. This review article delves into the contribution of hypoxia-associated genes and oxidative-stress-related factors to tendon degeneration, offering insights into potential therapeutic strategies. The unique aspect of this study lies in its pathway-based evidence, which sheds light on how these factors can be targeted to enhance overall tendon health.
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Affiliation(s)
- Hamzah Shahid
- Dongtan Sacred Heart Hospital, Hallym University, Hwaseong-si 18450, Gyeonggi-do, Republic of Korea (J.-H.K.)
- School of Medicine, Hallym University, Chuncheon City 24252, Gangwon-do, Republic of Korea
| | - Vivek Kumar Morya
- Dongtan Sacred Heart Hospital, Hallym University, Hwaseong-si 18450, Gyeonggi-do, Republic of Korea (J.-H.K.)
| | - Ji-Ung Oh
- Dongtan Sacred Heart Hospital, Hallym University, Hwaseong-si 18450, Gyeonggi-do, Republic of Korea (J.-H.K.)
| | - Jae-Hyung Kim
- Dongtan Sacred Heart Hospital, Hallym University, Hwaseong-si 18450, Gyeonggi-do, Republic of Korea (J.-H.K.)
| | - Kyu-Cheol Noh
- Dongtan Sacred Heart Hospital, Hallym University, Hwaseong-si 18450, Gyeonggi-do, Republic of Korea (J.-H.K.)
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10
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Deng X, Li Q, Yuan H, Hu H, Fan S. Galangin Promotes Tendon Repair Mediated by Tendon-Derived Stem Cells through Activating the TGF-β1/Smad3 Signaling Pathway. Chem Pharm Bull (Tokyo) 2024; 72:669-675. [PMID: 39010213 DOI: 10.1248/cpb.c24-00117] [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: 07/17/2024]
Abstract
Tendon injury is a prevalent orthopedic disease that currently lacks effective treatment. Galangin (GLN) is a vital flavonoid found abundantly in galangal and is known for its natural activity. This study aimed to investigate the GLN-mediated molecular mechanism of tendon-derived stem cells (TDSCs) in tendon repair. The TDSCs were characterized using alkaline phosphatase staining, alizarin red S staining, oil red O staining, and flow cytometry. The effect of GLN treatment on collagen deposition was evaluated using Sirius red staining and quantitative (q)PCR, while a Western bot was used to assess protein levels and analyze pathways. Results showed that GLN treatment not only increased the collagen deposition but also elevated the mRNA expression and protein levels of multiple tendon markers like collagen type I alpha 1 (COL1A1), decorin (DCN) and tenomodulin (TNMD) in TDSCs. Moreover, GLN was also found to upregulate the protein levels of transforming growth factor β1 (TGF-β1) and p-Smad3 to activate the TGF-β1/Smad3 signaling pathway, while GLN mediated collagen deposition in TDSCs was reversed by LY3200882, a TGF-β receptor inhibitor. The study concluded that GLN-mediated TDSCs enhanced tendon repair by activating the TGF-β1/Smad3 signaling pathway, suggesting a novel therapeutic option in treating tendon repair.
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Affiliation(s)
- Xiongwei Deng
- Department of Foot and Ankle Surgery, Nanchang Hongdu Hospital of Traditional Chinese Medicine
| | - Qiang Li
- Department of Foot and Ankle Surgery, Nanchang Hongdu Hospital of Traditional Chinese Medicine
| | - Haitao Yuan
- Department of Foot and Ankle Surgery, Nanchang Hongdu Hospital of Traditional Chinese Medicine
| | - Hejun Hu
- Department of Foot and Ankle Surgery, Nanchang Hongdu Hospital of Traditional Chinese Medicine
| | - Shaoyong Fan
- Department of Foot and Ankle Surgery, Nanchang Hongdu Hospital of Traditional Chinese Medicine
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11
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Xue Y, Riva N, Zhao L, Shieh JS, Chin YT, Gatt A, Guo JJ. Recent advances of exosomes in soft tissue injuries in sports medicine: A critical review on biological and biomaterial applications. J Control Release 2023; 364:90-108. [PMID: 37866405 DOI: 10.1016/j.jconrel.2023.10.031] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 10/08/2023] [Accepted: 10/19/2023] [Indexed: 10/24/2023]
Abstract
Sports medicine is generally associated with soft tissue injuries including muscle injuries, meniscus and ligament injuries, tendon ruptures, tendinopathy, rotator cuff tears, and tendon-bone healing during injuries. Tendon and ligament injuries are the most common sport injuries accounting for 30-40% of all injuries. Therapies for tendon injuries can be divided into surgical and non-surgical methods. Surgical methods mainly depend on the operative procedures, the surgeons and postoperative interventions. In non-surgical methods, cell therapy with stem cells and cell-free therapy with secretome of stem cell origin are current directions. Exosomes are the main paracrine factors of mesenchymal stem cells (MSCs) containing biological components such as proteins, nucleic acids and lipids. Compared with MSCs, MSC-exosomes (MSC-exos) possess the capacity to escape phagocytosis and achieve long-term circulation. In addition, the functions of exosomes from various cell sources in soft tissue injuries in sports medicine have been gradually revealed in recent years. Along with the biological and biomaterial advances in exosomes, exosomes can be designed as drug carriers with biomaterials and exosome research is providing promising contributions in cell biology. Exosomes with biomaterial have the potential of becoming one of the novel therapeutic modalities in regenerative researches. This review summarizes the derives of exosomes in soft tissue regeneration and focuses on the biological and biomaterial mechanism and advances in exosomal therapy in soft tissue injuries.
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Affiliation(s)
- Yulun Xue
- Department of Orthopaedic Surgery, Suzhou Municipal Hospital/The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou 215006, Jiangsu, PR China; Department of Orthopedics and Sports Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, PR China
| | - Nicoletta Riva
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - Lingying Zhao
- Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health of PR China, Suzhou 215006, Jiangsu, PR China; Department of Hematology, National Clinical Research Center for Hematologic Disease, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, PR China
| | - Ju-Sheng Shieh
- Department of Periodontology, School of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei City 11490, Taiwan
| | - Yu-Tang Chin
- Department of Periodontology, School of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei City 11490, Taiwan
| | - Alexander Gatt
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; Department of Haematology, Mater Dei Hospital, Msida, Malta
| | - Jiong Jiong Guo
- Department of Orthopedics and Sports Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, PR China; Department of Hematology, National Clinical Research Center for Hematologic Disease, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, PR China.
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12
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Lu J, Chen H, Lyu K, Jiang L, Chen Y, Long L, Wang X, Shi H, Li S. The Functions and Mechanisms of Tendon Stem/Progenitor Cells in Tendon Healing. Stem Cells Int 2023; 2023:1258024. [PMID: 37731626 PMCID: PMC10509002 DOI: 10.1155/2023/1258024] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 08/20/2023] [Accepted: 08/24/2023] [Indexed: 09/22/2023] Open
Abstract
Tendon injury is one of the prevalent disorders of the musculoskeletal system in orthopedics and is characterized by pain and limitation of joint function. Due to the difficulty of spontaneous tendon healing, and the scar tissue and low mechanical properties that usually develops after healing. Therefore, the healing of tendon injury remains a clinical challenge. Although there are a multitude of approaches to treating tendon injury, the therapeutic effects have not been satisfactory to date. Recent studies have shown that stem cell therapy has a facilitative effect on tendon healing. In particular, tendon stem/progenitor cells (TSPCs), a type of stem cell from tendon tissue, play an important role not only in tendon development and tendon homeostasis, but also in tendon healing. Compared to other stem cells, TSPCs have the potential to spontaneously differentiate into tenocytes and express higher levels of tendon-related genes. TSPCs promote tendon healing by three mechanisms: modulating the inflammatory response, promoting tenocyte proliferation, and accelerating collagen production and balancing extracellular matrix remodeling. However, current investigations have shown that TSPCs also have a negative effect on tendon healing. For example, misdifferentiation of TSPCs leads to a "failed healing response," which in turn leads to the development of chronic tendon injury (tendinopathy). The focus of this paper is to describe the characteristics of TSPCs and tenocytes, to demonstrate the roles of TSPCs in tendon healing, while discussing the approaches used to culture and differentiate TSPCs. In addition, the limitations of TSPCs in clinical application and their potential therapeutic strategies are elucidated.
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Affiliation(s)
- Jingwei Lu
- School of Physical Education, Southwest Medical University, Luzhou, China
| | - Hui Chen
- Geriatric Department, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Kexin Lyu
- School of Physical Education, Southwest Medical University, Luzhou, China
| | - Li Jiang
- School of Physical Education, Southwest Medical University, Luzhou, China
| | - Yixuan Chen
- School of Physical Education, Southwest Medical University, Luzhou, China
| | - Longhai Long
- Spinal Surgery Department, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Xiaoqiang Wang
- Spinal Surgery Department, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Houyin Shi
- Spinal Surgery Department, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Sen Li
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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13
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Qu F, Shen X, Wang K, Sun C, Li P. Tenogenic differentiation of human tendon-derived stem cells induced by long non-coding RNA LINCMD1 via miR-342-3p/EGR1 axis. Connect Tissue Res 2023; 64:479-490. [PMID: 37287279 DOI: 10.1080/03008207.2023.2217258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 05/16/2023] [Indexed: 06/09/2023]
Abstract
BACKGROUND Tendon-derived stem cells (TDSCs) are proposed as a potential cell-seed for the treatment of tendon injury due to their tenogenic differentiation potential. In this work, we defined the action of long non-coding RNA (lncRNA) muscle differentiation 1 (LINCMD1) in tenogenic differentiation of human TDSCs (hTDSCs). METHODS Quantitative real-time PCR (qRT-PCR) was used to assess the levels of LINCMD1, microRNA (miR)-342-3p, and early growth response-1 (EGR1) mRNA. Cell proliferation was detected by the XTT colorimetric assay. Protein expression was quantified by western blot. hTDSCs were grown in an osteogenic medium to induce osteogenic differentiation, and the extent of osteogenic differentiation was assessed by Alizarin Red Staining (ARS). The activity of alkaline phosphatase (ALP) was measured by the ALP Activity Assay Kit. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-342-3p and LINCMD1 or EGR1. RESULTS Our results showed that enforced expression of LINCMD1 or suppression of miR-342-3p accelerated the proliferation and tenogenic differentiation and reduced osteogenic differentiation of hTDSCs. LINCMD1 regulated miR-342-3p expression by binding to miR-342-3p. EGR1 was identified as a direct and functional target of miR-342-3p, and knockdown of EGR1 reversed the effects of miR-342-3p suppression on cell proliferation and tenogenic and osteogenic differentiation. Furthermore, the miR-342-3p/EGR1 axis mediated the regulation of LINCMD1 on hTDSC proliferation and tenogenic and osteogenic differentiation. CONCLUSION Our study suggests the induction of LINCMD1 in tenogenic differentiation of hTDSCs through miR-342-3p/EGR1 axis.
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Affiliation(s)
- Feng Qu
- Department of Foot and ankle surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xuezhen Shen
- Department of Orthopedics, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, PR China
| | - Ketao Wang
- Department of Foot and ankle surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Chengyi Sun
- Department of Foot and ankle surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Pengfei Li
- Department of Foot and ankle surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Li C, Wang J, Yang W, Yu K, Hong J, Ji X, Yao M, Li S, Lu J, Chen Y, Yan S, Wu H, Ma C, Yu X, Jiang G, Liu A. 3D-printed hydrogel particles containing PRP laden with TDSCs promote tendon repair in a rat model of tendinopathy. J Nanobiotechnology 2023; 21:177. [PMID: 37268942 DOI: 10.1186/s12951-023-01892-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 04/11/2023] [Indexed: 06/04/2023] Open
Abstract
Long-term chronic inflammation after Achilles tendon injury is critical for tendinopathy. Platelet-rich plasma (PRP) injection, which is a common method for treating tendinopathy, has positive effects on tendon repair. In addition, tendon-derived stem cells (TDSCs), which are stem cells located in tendons, play a major role in maintaining tissue homeostasis and postinjury repair. In this study, injectable gelatine methacryloyl (GelMA) microparticles containing PRP laden with TDSCs (PRP-TDSC-GM) were prepared by a projection-based 3D bioprinting technique. Our results showed that PRP-TDSC-GM could promote tendon differentiation in TDSCs and reduce the inflammatory response by downregulating the PI3K-AKT pathway, thus promoting the structural and functional repair of tendons in vivo.
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Affiliation(s)
- Congsun Li
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Jie Wang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Weinan Yang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Kang Yu
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Hangzhou, Zhejiang, PR China
| | - Jianqiao Hong
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Xiaoxiao Ji
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
| | - Minjun Yao
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Sihao Li
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Jinwei Lu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Yazhou Chen
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Shigui Yan
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Haobo Wu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Chiyuan Ma
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China
| | - Xiaohua Yu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China.
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China.
| | - Guangyao Jiang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China.
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China.
| | - An Liu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.
- Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China.
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, PR China.
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15
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The Influence of Different Modes of Exercise on Healthy and Injured Tendons. Stem Cells Int 2022; 2022:3945210. [PMID: 36117720 PMCID: PMC9481386 DOI: 10.1155/2022/3945210] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 07/03/2022] [Accepted: 08/25/2022] [Indexed: 11/17/2022] Open
Abstract
Tendons are essential components of the musculoskeletal system that links the skeletal muscle to the skeleton. This dense connective tissue exhibits great plasticity. Therefore, research on the influence of types of exercise, including acute and long-term training, on the structural and mechanical properties of tendons in athletic and sedentary populations is of critical importance in the design of scientific-based exercise plans and effective tendinopathy treatment. Here, we review recent studies on the relationship between exercise and tendon health and tendinopathy repair to provide a general understanding of how exercise may reshape tendons.
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Tang Y, Wang Z, Xiang L, Zhao Z, Cui W. Functional biomaterials for tendon/ligament repair and regeneration. Regen Biomater 2022; 9:rbac062. [PMID: 36176715 PMCID: PMC9514853 DOI: 10.1093/rb/rbac062] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/30/2022] [Accepted: 08/13/2022] [Indexed: 11/29/2022] Open
Abstract
With an increase in life expectancy and the popularity of high-intensity exercise, the frequency of tendon and ligament injuries has also increased. Owing to the specificity of its tissue, the rapid restoration of injured tendons and ligaments is challenging for treatment. This review summarizes the latest progress in cells, biomaterials, active molecules and construction technology in treating tendon/ligament injuries. The characteristics of supports made of different materials and the development and application of different manufacturing methods are discussed. The development of natural polymers, synthetic polymers and composite materials has boosted the use of scaffolds. In addition, the development of electrospinning and hydrogel technology has diversified the production and treatment of materials. First, this article briefly introduces the structure, function and biological characteristics of tendons/ligaments. Then, it summarizes the advantages and disadvantages of different materials, such as natural polymer scaffolds, synthetic polymer scaffolds, composite scaffolds and extracellular matrix (ECM)-derived biological scaffolds, in the application of tendon/ligament regeneration. We then discuss the latest applications of electrospun fiber scaffolds and hydrogels in regeneration engineering. Finally, we discuss the current problems and future directions in the development of biomaterials for restoring damaged tendons and ligaments.
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Affiliation(s)
- Yunkai Tang
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P. R. China
| | - Zhen Wang
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P. R. China
| | - Lei Xiang
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P. R. China
| | - Zhenyu Zhao
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P. R. China
| | - Wenguo Cui
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P. R. China
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17
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Ferdousi F, Sasaki K, Xu D, Zheng YW, Szele FG, Isoda H. Editorial: Directing Stem Cell Fate Using Plant Extracts and Their Bioactive Compounds. Front Cell Dev Biol 2022; 10:957601. [PMID: 35846354 PMCID: PMC9277474 DOI: 10.3389/fcell.2022.957601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 06/08/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Farhana Ferdousi
- AIST-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), AIST, University of Tsukuba, Tsukuba, Japan
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan
| | - Kazunori Sasaki
- AIST-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), AIST, University of Tsukuba, Tsukuba, Japan
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan
| | - Dongzhu Xu
- AIST-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), AIST, University of Tsukuba, Tsukuba, Japan
- Cardiovascular Division, Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Yun-Wen Zheng
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Francis G Szele
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
| | - Hiroko Isoda
- AIST-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), AIST, University of Tsukuba, Tsukuba, Japan
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan
- Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan
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Shengnan Q, Bennett S, Wen W, Aiguo L, Jiake X. The role of tendon derived stem/progenitor cells and extracellular matrix components in the bone tendon junction repair. Bone 2021; 153:116172. [PMID: 34506992 DOI: 10.1016/j.bone.2021.116172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 08/22/2021] [Accepted: 09/02/2021] [Indexed: 12/29/2022]
Abstract
Fibrocartilage enthesis is the junction between bone and tendon with a typical characteristics of fibrocartilage transition zones. The regeneration of this transition zone is the bottleneck for functional restoration of bone tendon junction (BTJ). Biomimetic approaches, especially decellularized extracellular matrix (ECM) materials, are strategies which aim to mimic the components of tissues to the utmost extent, and are becoming popular in BTJ healing because of their ability not only to provide scaffolds to allow cells to attach and migrate, but also to provide a microenvironment to guide stem/progenitor cells lineage-specific differentiation. However, the cellular and molecular mechanisms of those approaches, especially the ECM proteins, remain unclear. For BTJ reconstruction, fibrocartilage regeneration is the key for good integrity of bone and tendon as well as its mechanical recovery, so the components which can guide stem cells to a chondrogenic commitment in biomimetic approaches might well be the key for fibrocartilage regeneration and eventually for the better BTJ healing. In this review, we firstly discuss the importance of cartilage-like formation in the healing process of BTJ. Next, we explore the possibility of tendon-derived stem/progenitor cells as cell sources for BTJ regeneration due to their multi-differentiation potential. Finally, we summarize the role of extracellular matrix components of BTJ in guiding stem cell fate to a chondrogenic commitment, so as to provide cues for understanding the mechanisms of lineage-specific potential of biomimetic approaches as well as to inspire researchers to incorporate unique ECM components that facilitate BTJ repair into design.
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Affiliation(s)
- Qin Shengnan
- Guangzhou Institute of Traumatic Surgery, Department of Orthopedics, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, China
| | - Samuel Bennett
- School of Biomedical Sciences, The University of Western Australia, Perth, Australia
| | - Wang Wen
- Guangzhou Institute of Traumatic Surgery, Department of Orthopedics, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, China
| | - Li Aiguo
- Guangzhou Institute of Traumatic Surgery, Department of Orthopedics, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, China.
| | - Xu Jiake
- School of Biomedical Sciences, The University of Western Australia, Perth, Australia.
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