组织工程化肱二头肌自体肌腱补片增强了兔冈下肌腱缺损模型的肩袖大面积缺损修复。

IF 4.2 2区 医学 Q1 ORTHOPEDICS
Youguo Liao, Hengzhi Liu, Jiayun Huang, Zetao Wang, Tao Zhang, Xiangjun Hu, Qiulin He, Zichen Wang, Yang Fei, Yuxiang Zhang, Fangyuan Cai, Dengfeng Ruan, Hong Zhang, Luyong Jiang, Zi Yin, Hongwei Ouyang, Xiao Chen, Weiliang Shen
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The in vivo animal study was conducted using 8- to 12-week-old New Zealand White rabbits. The left shoulder of each animal was operated on, with equal numbers of males and females. There were 12 rabbits in the control group and 15 rabbits each in the gel and patch groups. Six rabbits were allocated to each of the three groups at the 1- and 3-month time points and three rabbits each were in the gel and patch groups at 2-month time point. Through an infraspinatus tendon defect model, the effectiveness of tissue-engineered bicipital autologous tendon patches (patch group) in tendon repair was assessed compared with untreated (control group) and fibrin glue (gel group) treatments in vivo. 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引用次数: 0

摘要

背景:肩袖大块缺损是肩部疼痛和功能障碍的重要原因,严重降低了患者的生活质量。肩袖大面积缺损的主要治疗方法包括完全或部分修复和补片增量。然而,由于肌腱的再生能力有限,肩袖缺损修复后肌腱再撕裂的风险仍然很高。因此,需要一种新疗法来促进肌腱再生,以修复大面积肩袖缺损:通过体外分析,我们首先提出了以下问题:(1)纤维蛋白胶的生物相容性和胶原合成能力如何,由纤维蛋白胶和肱二头肌肌腱组织颗粒组成的组织工程肱二头肌肌腱补片的细胞生长情况如何?然后,利用新西兰白兔冈下肌腱全厚缺损的体内动物模型,我们提出了以下问题:(2)组织工程双腱鞘自体肌腱补片促进肌腱再生的潜力如何?我们进行了体外实验,以评估在纤维蛋白胶中培养的肌腱干/祖细胞的存活、增殖和胶原合成能力。分别通过活/死细胞存活率检测、细胞计数试剂盒-8(CCK-8)检测和天狼星红染色来实现。体内动物研究使用的是 8 至 12 周大的新西兰白兔。每只兔子的左肩都接受了手术,雌雄数量相等。对照组有 12 只兔子,凝胶组和贴片组各有 15 只兔子。在 1 个月和 3 个月的时间点,三组各分配 6 只兔子,在 2 个月的时间点,凝胶组和贴片组各分配 3 只兔子。通过冈下肌腱缺损模型,评估了组织工程双膝自体肌腱贴片(贴片组)与未处理组(对照组)和纤维蛋白胶(凝胶组)的肌腱修复效果。评估包括修复组织形态的组织学评估、再生胶原纤维的透射电子显微镜(TEM)评估以及 RNA 测序,以探索组织工程双腱鞘自体肌腱贴片在肌腱再生中的潜在机制:体外实验表明,与单独的标准细胞培养(0.27 ± 0.02,平均差 0.11 [95% CI 0.07 至 0.14];p < 0.001)相比,纤维蛋白胶增强了肌腱干细胞/祖细胞的胶原合成能力(0.38 ± 0.02)。随着培养时间的延长,培养 14 天后(78.13%±3.68%)与培养 11 天(13.05%±8.78%,平均差-65.08%[95%CI-77.99%至-52.15%];p<0.001)、7天(2.67%±2.62%,平均差异-75.46%[95%CI-88.37%至-62.53%];p<0.001)和1天(0.33%±0.30%,平均差异-77.80%[95%CI-90.71%至-64.87%];p<0.001)。移植后 3 个月的体内实验显示,与对照组和凝胶组相比,贴片组的修复效果更好。与凝胶组(10.67 ± 0.58,平均差 6.84 [95% CI 3.67 至 10.00];p = 0.001)和对照组(10.75 ± 0.66,平均差 6.92 [95% CI 3.75 to 10.08]; p = 0.001),以及补片组(77.52 ± 44.41 nm)与对照组(53.34 ± 6.64 nm,平均差 24.18 [95% CI 22.24 to 26.11]; p < 0.001)相比,新形成的胶原纤维排列规则且直径更大。RNA 测序分析表明,组织工程双腱鞘自体肌腱补片通过调节免疫反应、促进胶原纤维组织和减轻血管收缩促进了肌腱再生:这项动物研究表明,组织工程双腱鞘自体肌腱补片可有效调节免疫反应和胶原纤维组织,从而促进肌腱再生:组织工程双腱鞘自体肌腱补片是一种很有前景的肌腱再生策略,在临床肩袖手术中修复肩袖大面积缺损方面具有潜力。后续研究可侧重于使用组织工程双腱鞘自体肌腱补片进行大型动物实验,以探索其临床转化的可行性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tissue-engineered Bicipital Autologous Tendon Patch Enhances Massive Rotator Cuff Defect Repair in a Rabbit Infraspinatus Tendon Defect Model.

Background: Massive rotator cuff defects represent an important source of shoulder pain and functional debilitation, substantially diminishing patients' quality of life. The primary treatment of massive rotator cuff defects includes complete or partial repair and patch augmentation. However, because of the tendon's limited regenerative ability, the tendon retear risk after rotator cuff defect repair is still high. Thus, a new therapy is needed to promote tendon regeneration for repair of massive rotator cuff defects.

Questions/purposes: Using an in vitro analysis, we first asked: (1) What is the biocompatibility and collagen synthesis ability of fibrin glue, and what is the cell growth of tissue-engineered bicipital tendon patches, which is comprised of fibrin glue and biceps tendon tissue particles? Then, using an in vivo animal model of full-thickness defects in the infraspinatus tendon in New Zealand White rabbits, we asked: (2) What is the potential of the tissue-engineered bicipital autologous tendon patch to promote tendon regeneration?

Methods: In vitro experiments were conducted to assess the survival, proliferation, and collagen synthesis ability of tendon stem/progenitor cells cultured in fibrin glue. This was achieved through an assay of live/dead cell viability, cell counting kit-8 (CCK-8) assay, and Sirius red staining, respectively. The in vivo animal study was conducted using 8- to 12-week-old New Zealand White rabbits. The left shoulder of each animal was operated on, with equal numbers of males and females. There were 12 rabbits in the control group and 15 rabbits each in the gel and patch groups. Six rabbits were allocated to each of the three groups at the 1- and 3-month time points and three rabbits each were in the gel and patch groups at 2-month time point. Through an infraspinatus tendon defect model, the effectiveness of tissue-engineered bicipital autologous tendon patches (patch group) in tendon repair was assessed compared with untreated (control group) and fibrin glue (gel group) treatments in vivo. This assessment included histological evaluation of repaired tissue morphology, transmission electron microscopy (TEM) evaluation of regenerated collagen fibrils, and RNA sequencing to explore the potential mechanisms of tissue-engineered bicipital autologous tendon patches in tendon regeneration.

Results: In vitro experiments demonstrated that fibrin glue enhanced the collagen synthesis ability of tendon stem/progenitor cells (0.38 ± 0.02) compared with standard cell culture alone (0.27 ± 0.02, mean difference 0.11 [95% CI 0.07 to 0.14]; p < 0.001). With prolonged cultivation, the cell growth area of tissue-engineered bicipital tendon patches showed a notable increase after culturing for 14 days (78.13% ± 3.68%) compared with 11 days (13.05% ± 8.78%, mean difference -65.08% [95% CI -77.99% to -52.15%]; p󿇀001), 7 days (2.67% ± 2.62%, mean difference -75.46% [95% CI -88.37% to -62.53%]; p󿇀001), and 1 day (0.33% ± 0.30%, mean difference -77.80% [95% CI -90.71% to -64.87%]; p<0.001). At 3 months after transplantation, in vivo experiments revealed that compared with the control and gel groups, the patch group displayed improved repair outcomes. This was evidenced by better histological scores in the patch group (3.83 ± 2.01) compared with the gel group (10.67 ± 0.58, mean difference 6.84 [95% CI 3.67 to 10.00]; p = 0.001) and control group (10.75 ± 0.66, mean difference 6.92 [95% CI 3.75 to 10.08]; p = 0.001), and by regular alignment and larger diameters of newly formed collagen fibrils in the patch group (77.52 ± 44.41 nm) compared with the control group (53.34 ± 6.64 nm, mean difference 24.18 [95% CI 22.24 to 26.11]; p < 0.001). RNA sequencing analysis revealed that a tissue-engineered bicipital autologous tendon patch facilitated tendon regeneration by modulating the immune response, promoting collagen fibril organization, and alleviating vasoconstriction.

Conclusion: This animal study demonstrates that the tissue-engineered bicipital autologous tendon patch effectively modulates an immune response and collagen fibril organization, leading to the promotion of tendon regeneration.

Clinical relevance: The tissue-engineered bicipital autologous tendon patch represents a promising strategy for tendon regeneration, offering potential in the repair of massive rotator cuff defects during clinical rotator cuff surgery. Subsequent research could focus on large animal experiments using a tissue-engineered bicipital autologous tendon patch to explore their feasibility for clinical translation.

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来源期刊
CiteScore
7.00
自引率
11.90%
发文量
722
审稿时长
2.5 months
期刊介绍: Clinical Orthopaedics and Related Research® is a leading peer-reviewed journal devoted to the dissemination of new and important orthopaedic knowledge. CORR® brings readers the latest clinical and basic research, along with columns, commentaries, and interviews with authors.
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