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经细胞化处理的猪跟腱贴片包裹肌腱源性干细胞,用于兔模型肩袖修复。

Acellular porcine Achilles tendon patch encapsulating tendon-derived stem cells for rotator cuff repair in a rabbit model.

机构信息

Wuhan Fourth Hospital, Wuhan, 430030, China.

Wuhan Sports Medicine Center, Wuhan, 430030, China.

出版信息

Sci Rep. 2024 Mar 27;14(1):7257. doi: 10.1038/s41598-024-57495-z.

DOI:10.1038/s41598-024-57495-z
PMID:38538703
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10973360/
Abstract

Currently, the predominant method for repairing rotator cuff involves surgical suture techniques, but the failure rate remains notably high. Failure of the rotator cuff insertion to provide adequate biomechanics during early healing is considered a major cause of failure. Addressing this problem, biological augmentation emerges as a promising strategy for enhancing the biomechanical properties during early stages. Tendon-derived stem cells (TDSCs), which facilitate the differentiation of repair-supportive cells, hold the potential to improve the efficacy of patch application. The study aims to assess the behavior of TDSCs in acellular porcine Achilles tendon (APAT) patches and to explore the capacity of the APAT patch encapsulating TDSCs in promoting both tendon-to-bone healing and biomechanical enhancements in a rabbit rotator cuff repair model. Transmission electron microscopy (TEM) analyses validated the complete cellular clearance of native cells from APAT patches, with uniform distribution of TDSCs. Immunofluorescence staining confirmed successful TDSCs attachment, while population doubling time (PDT) underscored increased TDSCs proliferation on APAT patches. Quantitative polymerase chain reaction (qPCR) demonstrated upregulation of tenocyte and osteocyte related genes in TDSCS cultured within the patches. In the subsequent in vivo experiment, fifty-four rabbits were used to create rotator cuff injury models and randomly assigned to a control group, an APAT patch group, and an APAT patch with TDSCs group. Histological analysis showed that the APAT patch with TDSCs group had significantly enhanced tendon-to-bone healing and a distinctly organized tendon-fibrocartilage-bone structure, as compared to the APAT patch group. In addition, the biomechanical properties of the APAT patch with TDSCs group were significantly improved. In conclusion, APAT patches promote TDSC proliferation and stimulate tenogenic and osteogenic differentiation. APAT patches encapsulating TDSCs have shown considerable potential in promoting tendon-to-bone healing of rotator cuff injuries, indicating that their use in rotator cuff repair surgery is clinically meaningful.

摘要

目前,修复肩袖撕裂的主要方法是手术缝合技术,但失败率仍然很高。肩袖插入物在早期愈合过程中不能提供足够的生物力学性能被认为是失败的主要原因。为了解决这个问题,生物增强被认为是一种在早期阶段增强生物力学特性的有前途的策略。肌腱衍生干细胞(TDSCs)可以促进修复支持细胞的分化,有可能提高补片应用的效果。本研究旨在评估 TDSCs 在脱细胞猪跟腱(APAT)补片中的行为,并探讨 APAT 补片包封 TDSCs 促进兔肩袖修复模型中的腱骨愈合和生物力学增强的能力。透射电子显微镜(TEM)分析验证了 APAT 补片中天然细胞的完全细胞清除,TDSCs 分布均匀。免疫荧光染色证实了 TDSCs 的成功附着,而倍增时间(PDT)强调了 TDSCs 在 APAT 补片上的增殖增加。定量聚合酶链反应(qPCR)显示在补片中培养的 TDSCs 中上调了肌腱细胞和成骨细胞相关基因。在随后的体内实验中,使用 54 只兔子建立肩袖损伤模型,并随机分为对照组、APAT 补片组和 APAT 补片加 TDSCs 组。组织学分析表明,与 APAT 补片组相比,APAT 补片加 TDSCs 组具有明显增强的腱骨愈合和明显组织化的腱纤维软骨骨结构。此外,APAT 补片加 TDSCs 组的生物力学性能得到了显著改善。总之,APAT 补片促进 TDSC 增殖,并刺激肌腱和成骨分化。APAT 补片包封 TDSCs 在促进肩袖损伤的腱骨愈合方面显示出相当大的潜力,表明其在肩袖修复手术中的应用具有临床意义。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9726/10973360/03cb6a00b9c4/41598_2024_57495_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9726/10973360/29e92a37664a/41598_2024_57495_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9726/10973360/7bee32c3b9f7/41598_2024_57495_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9726/10973360/0a9c0a5b85d2/41598_2024_57495_Fig9_HTML.jpg
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