Background:Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues.Purpose:To fabricate a tendon stem cell–derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo.Study Design:Controlled laboratory study.Methods:TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)–based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in vitro by culturing them in saline, PCL-based scaffold (S), COL-I loaded scaffold (COL-I-S), and TSC-Exos-S. In vivo studies were conducted on a rabbit UMRCT model, where bridging was repaired with S, COL-I-S, TSC-Exos-S, and autologous fascia lata (FL). Histological and biomechanical analyses were performed at 8 and 16 weeks postoperatively.Results:TSC-Exos-S exhibited reliable mechanical strength and subcutaneous degradation, which did not occur before tissue regeneration. TSC-Exos-S significantly promoted the proliferation, migration, and tenogenic differentiation of rabbit BMSCs in vitro. In vivo studies showed that UMRCT repaired with TSC-Exos-S exhibited significant signs of tendinous tissue regeneration at the bridging site with regard to specific collagen staining. Moreover, no significant differences were observed in the histological and biomechanical properties compared with those repaired with autologous FL.Conclusion:TSC-Exos-S achieved tendinous tissue regeneration in UMRCT by providing mechanical support and promoting the trend toward tenogenic differentiation.Clinical Relevance:The present study proposes a potential strategy for repairing UMRCT with severely retracted musculotendinous tissues and large tendinous tissue defects.

中文翻译：

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肌腱干细胞衍生的外泌体加载支架的 3 维生物打印，以桥接不可修复的大规模肩袖撕裂


背景：由于肩袖肌腱组织严重回缩以及肩袖肌腱组织的极端缺陷，不可修复的大面积肩袖撕裂（UMRCT）对外科医生来说是一个挑战。目的：制造肌腱干细胞衍生的外泌体负载支架（TSC-Exos） -S) 并研究其对体外细胞生物活性和体内兔 UMRCT 模型修复的影响。研究设计：对照实验室研究。方法：通过加载 TSC-Exos 和 1 型胶原 (COL- I) 到基于 3 维生物打印和聚己内酯 (PCL) 的支架中。通过在盐水、基于 PCL 的支架 (S)、COL-I 负载支架 (COL-I-S) 和 TSC- 中培养兔骨髓干细胞 (BMSC)，体外评估其增殖、迁移和肌腱分化活性。 Exos-S。在兔 UMRCT 模型上进行了体内研究，其中用 S、COL-I-S、TSC-Exos-S 和自体阔筋膜 (FL) 修复桥接。术后8周和16周进行组织学和生物力学分析。结果：TSC-Exos-S表现出可靠的机械强度和皮下降解，这在组织再生前不会发生。 TSC-Exos-S 显着促进体外兔 BMSC 的增殖、迁移和肌腱分化。体内研究表明，就特定胶原染色而言，用 TSC-Exos-S 修复的 UMRCT 在桥接部位表现出显着的肌腱组织再生迹象。此外，与自体 FL 修复相比，在组织学和生物力学特性方面没有观察到显着差异。结论：TSC-Exos-S 通过提供机械支撑和促进肌腱分化趋势，在 UMRCT 中实现肌腱组织再生。临床意义：本研究提出了修复严重回缩的肌腱组织和大肌腱组织缺损的 UMRCT 的潜在策略。