Journal of Orthopaedic Surgery and Research
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2025
·Vol. 20
·期 1
·1-12
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IF 2.8
He Zhenhong,Zeng Shengqiang,Qin Bo,Liu Gang,Liu Huan,Bao Dingsu
ObjectiveTendon injury is a common and frequent disease in the field of sports medicine, and tendon repair after injury is a common clinical difficulty. Repair strategy based on tendon stem cells (TDSCs) therapy is considered a promising therapeutic option for the treatment of tendon injuries. Icariin (ICA) has been shown to be an effective herbal monomer for the treatment of tendon-bone healing and may be effective in the repair of tendon injuries.Methods In vitro, TDSCs isolated from C57 mice were treated with ICA (0.01–100 µM) to assess proliferation (CCK-8 assay) and tendonogenic differentiation (qRT-PCR). In vivo, 42 C57 mice with surgically induced patellar tendon defects were randomized into three groups (n = 14/group): (1) 20 mg/kg ICA, (2) 40 mg/kg ICA, and (3) control group (DMSO), administered intraperitoneally for 14 days. Half of each group (n = 7) underwent histopathological (hematoxylin-eosin staining, Masson staining) and molecular (qRT-PCR) analyses at 2 and 4 weeks post-surgery.Results In vitro, after 7 days of ICA intervention in TDSC, the expression of Mohawk (MKX), Scleraxis (SCX), fibromodulin (FMOD), and Tenomodulin (TNC) were higher in the ICA group than in the control group. In vivo, the expression of MKX, SCX, FMOD, and TNC was higher in the 20 mg/kg ICA group and 40 mg/kg ICA group than in the control group at 2 and 4 weeks after surgery. Histological evaluation revealed superior tendon repair in both ICA-treated groups compared to controls at both 2 and 4 weeks postoperative intervals. The 20 mg/kg ICA group demonstrated a significant enhancement in tissue continuity and collagen fiber organization, exhibiting greater defect filling, fewer interstitial gaps, and reduced vascular infiltration. In contrast, control specimens exhibited disorganized collagen architecture with prominent interstitial gaps. The 40 mg/kg ICA group showed intermediate repair outcomes between the 20 mg/kg ICA and control groups.Conclusion ICA can improve tendon injury repair by enhancing tendonogenic differentiation of TDSC.
研究领域:
运动医学
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再生医学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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2022
·
IF 3.511
Qinghui Han,Shuguang Wang,Dawei Chen,Di Gan,Tao Wang
Tendon injuries are common clinical issues resulted from tissue overuse and age-related degeneration. Previous sutdies have suggested that exosomes secreted by mesenchymal stem cells (MSCs) contribute to tissue injury repair. Here, we provide evidence for a critical role of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes in reducing tendon injury by activating the RhoA signaling. Treatment of primary injured tenocytes with hucMSC exosomes increases cell proliferation and invasion, which correlates with increased RhoA activity. RhoA mediates the effects of hucMSC exosomes, as treatment of primary injured tenocytes with the RhoA inhibitor, CCG-1423, abolishes the effects of hucMSC exosomes on cell proliferation and invasion. Mechanistically, we observe that hucMSC exosomes induce the expression of a microRNA, miR-27b-3p, which targets and suppresses ARHGAP5, a negative regulator of RhoA. Consistent with this observation, ARHGAP5 overexpression suppresses the effects of hucMSC exosomes on cell proliferation and invasion, while knockdown of ARHGAP5 rescues these effects. Finally, we demonstrate the functional significance of our findings in vivo using an Achilles tendon injury model and show that treatment with exosomes reduces tendon injury in rats, which correlates with increased RhoA activity and reduced ARHGAP5 expression. Taken together, our findings highlight a critical role of hucMSC exosomes in reducing tendon injury via miR-27b-3p-mediated suppression of ARHGAP5, resulting in RhoA activation, and leading to increased cell proliferation and invasion of primary injured tenocytes.
研究领域:
干细胞生物学
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分子生物学
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再生医学
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骨科
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Zhen Ren,Zhiguang Duan,Zhuo Zhang,Rongzhan Fu,Chenhui Zhu,Daidi Fan
The treatment of tendon injuries is an important healthcare challenge. Irregular wounds, hypocellularity, and prolonged inflammation impede the rate of healing for tendon injuries. To address these problems, a high-tenacity shape-adaptive, mussel-like hydrogel (PH/ [email protected] &PDA) was designed and constructed with polyvinyl alcohol (PVA) and hyaluronic acid grafted with phenylboronic acid (BA-HA) by encapsulating polydopamine and gelatin microspheres containing basic fibroblast growth factor ( [email protected] ). The shape-adaptive PH/ [email protected] &PDA hydrogel can quickly adapt to irregular tendon wounds, and the strong adhesion (101.46 ± 10.88 kPa) can keep the hydrogel adhered to the wound at all times. In addition, the high tenacity and self-healing properties allow the hydrogel to move with the tendon without fracture. Additionally, even if fractured, it can quickly self-heal and continue to adhere to the tendon wound, while slowly releasing basic fibroblast growth factor during the inflammatory phase of the tendon repair process, promoting cell proliferation, migration and shortening the inflammatory phase. In acute tendon injury and chronic tendon injury models, PH/ [email protected] &PDA significantly alleviated inflammation and promoted collagen I secretion, enhancing wound healing through the synergistic effects of its shape-adaptive and high-adhesion properties.
研究领域:
生物医学工程
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组织工程
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材料科学
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药学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Cheng Peng,Shiqi Kang,Meijun Jiang,Mingxi Yang,Xu Gong
Background The formation of adhesion after tendon injury represents a major obstacle to tendon repair, and currently there is no effective anti-adhesion method in clinical practice. Oxidative stress, inflammation, and fibrosis can occur in tendon injury and these factors can lead to tendon adhesion. Antioxidant carbon dots and ursolic acid (UA) both possess antioxidant and anti-inflammatory properties. In this experiment, we have for the first time created RCDs/UA@Lipo-HAMA using red fluorescent carbon dots and UA co-encapsulated liposomes composite hyaluronic acid methacryloyl hydrogel. We found that RCDs/UA@Lipo-HAMA could better attenuate adhesion formation and enhance tendon healing in tendon injury.Materials and Methods RCDs/UA@Lipo-HAMA were prepared and characterized. In vitro experiments on cellular oxidative stress and fibrosis were performed. Reactive oxygen species (ROS), and immunofluorescent staining of collagens type I (COL I), collagens type III (COL III), and α-smooth muscle actin (α-SMA) were used to evaluate anti-oxidative and anti-fibrotic abilities. In vivo models of Achilles tendon injury repair (ATI) and flexor digitorum profundus tendon injury repair (FDPI) were established. The major organs and blood biochemical indicators of rats were tested to determine the toxicity of RCDs/UA@Lipo-HAMA. Biomechanical testing, motor function analysis, immunofluorescence, and immunohistochemical staining were performed to assess the tendon adhesion and repair after tendon injury.Results In vitro, the RCDs/UA@Lipo group scavenged excessive ROS, stabilized the mitochondrial membrane potential (ΔΨm), and reduced the expression of COL I, COL III, and α-SMA. In vivo, assessment results showed that the RCDs/UA@Lipo-HAMA group improved collagen arrangement and biomechanical properties, reduced tendon adhesion, and promoted motor function after tendon injury. Additionally, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the RCDs/UA@Lipo-HAMA group increased; the levels of cluster of differentiation 68 (CD68), inducible Nitric Oxide Synthase (iNOS), COL III, α-SMA, Vimentin, and matrix metallopeptidase 2 (MMP2) decreased.Conclusion In this study, the RCDs/UA@Lipo-HAMA alleviated tendon adhesion formation and enhanced tendon healing by attenuating oxidative stress, inflammation, and fibrosis. This study provided a novel therapeutic approach for the clinical treatment of tendon injury.
研究领域:
生物医学工程
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药学
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组织工程
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骨科
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伤口愈合
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
·
IF 13.3
Yingxue Jiang,Chenhui Zhu,Xiaoxuan Ma,Daidi Fan
To address the high complexity and challenging nature of large-scale tendon injury repair, an innovative Janus structured hydrogel patch (JAHP@bFGF) was designed in this study. The patch combines microenvironmental responsiveness with efficient repair function, aiming to optimise and accelerate the tendon healing process. The outer layer is a PVA/SA/Na 3 Cit hydrogel with excellent mechanical properties, protein resistance, and low friction, which provides firm support to the tendon and reduces adhesions to ensure the recovery of gliding function. The inner layer of TCSB@bFGF microgel responds intelligently to changes in the microenvironment, precisely regulates the release of bFGF, promotes cell proliferation and migration, accelerates tissue regeneration, and has high adhesion strength and antimicrobial properties, which significantly reduces the risk of postoperative infection. Experimental results show that JAHP@bFGF significantly optimises the healing process, accelerates the repair speed and improves the repair quality under simulated large-scale tendon injury conditions. The unique Janus surface design and the intelligent drug release function, in synergy, not only bring new hope to patients with large-scale tendon injuries, but also provide an important reference for the application of biomedical materials in the repair of complex tissues, which heralds the arrival of the era of more efficient and personalised tendon repair.
研究领域:
生物医学工程
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组织工程
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材料科学
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再生医学
✓ 已验证
DOI
高影响因子
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