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通过可注射自修复水凝胶中镁/姜黄素的持续释放产生的抗炎和促进分化作用协同增强肌腱-骨愈合。

Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg/curcumin from injectable self-healing hydrogels.

机构信息

Department of Orthopaedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.

Frontier Institute of Science and Technology, and State Key Laboratory for Mechanical Behavior of Materials, and Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710049, China.

出版信息

Theranostics. 2021 Apr 3;11(12):5911-5925. doi: 10.7150/thno.56266. eCollection 2021.

DOI:10.7150/thno.56266
PMID:33897889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8058719/
Abstract

Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing. In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated and . Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests. The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing. The composite hydrogel mediated sustained release of curcumin and Mg to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.

摘要

肩袖重建后愈合反应不良是多因素的,病变部位的炎症微环境和干细胞分化因子缺乏与愈合不良最相关。然而,目前缺乏有效的组织工程策略,既能发挥抗炎作用,又能促进分化,从而促进肩袖愈合。在本研究中,我们合成并表征了一种新型的活性药物递送载体,成功克服了同时高效装载和控制镁和姜黄素释放的挑战。评估了复合水凝胶的抗炎和促分化作用。此外,通过组织学、免疫荧光和生物力学测试研究了肩袖腱骨界面的愈合情况。复合水凝胶表现出优异的生物相容性和可注射性、良好的粘附性和快速的自修复能力。释放的姜黄素表现出明显的抗炎和抗氧化作用,保护了干细胞和腱基质。此外,释放的镁促进了干细胞的聚集和软骨形成。此外,手术后 8 周大鼠肩袖撕裂模型的生物力学测试和组织学结果表明,复合水凝胶显著增强了腱骨愈合。复合水凝胶介导姜黄素和镁的持续释放,通过抗炎和促分化作用有效促进肩袖腱骨愈合。因此,这种复合水凝胶为肩袖修复提供了很好的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/8058719/1d7e44a1661e/thnov11p5911g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/8058719/1d7e44a1661e/thnov11p5911g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/8058719/92bb2b7283d0/thnov11p5911g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/8058719/2e0934bc4751/thnov11p5911g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/8058719/1d7e44a1661e/thnov11p5911g009.jpg

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