Background:

Retraction and degenerative changes of chronic rotator cuff tears limit the healing capacity after routine surgical repair.

Purpose:

To fabricate a mesenchymal stem cell–derived exosome (MSC–Exos) loaded patch and evaluate the effect of this patch on the activity of rabbit tenocytes in vitro and on the repair of chronic rotator cuff tears associated with degenerative changes in vivo.

Study Design:

Controlled laboratory study.

Methods:

The MSC–Exos loaded patch was fabricated using a dynamic wet-spinning system. In the in vitro studies, the proliferation and migration activities of tenocytes were evaluated by culturing tenocytes with saline, a fiber-aligned patch, or an MSC–Exos loaded patch. In the in vivo studies, a rabbit model of chronic rotator cuff tear was established and directly repaired, repaired with fiber-aligned patch augmentation (RFPA group), and repaired with MSC–Exos loaded patch augmentation (REPA group). Histological and biomechanical analyses were performed at 4, 8, and 12 weeks after surgery.

Results:

An MSC–Exos loaded patch with inner aligned fibers, a loose microstructure, and reliable initial strength was fabricated using a dynamic wet-spinning system. The MSC–Exos loaded patch significantly promoted tenocyte proliferation and migration activities in vitro. In vivo, the REPA group exhibited significantly higher tendon maturing scores at 8 and 12 weeks after surgery compared with both the control and the RFPA groups. Fatty infiltration was significantly reduced in the REPA group at 4, 8, and 12 weeks compared with both the control and the RFPA groups. Biomechanical properties, including load to failure and stress, were also significantly improved at 12 weeks in the REPA group compared with both the control and the RFPA groups.

Conclusion:

Results in the present study suggested that an MSC–Exos loaded patch was able to enhance the repair of a chronic rotator cuff tear by providing mechanical support and minimizing degeneration.

Clinical Relevance:

This work supported the idea that loading bioactive MSC–Exos into a traditionally designed rotator cuff patch might exert a better effect on the repair of chronic rotator cuff tears than augmented patch repair alone.

中文翻译：

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将间充质干细胞衍生的外泌体加载到传统设计的肩袖贴片中：增强与退行性变化相关的慢性肩袖撕裂修复的潜在策略

背景：

慢性肩袖撕裂的回缩和退行性变化限制了常规手术修复后的愈合能力。

目的：

制造间充质干细胞衍生的外泌体 (MSC-Exos) 加载贴片，并评估该贴片对体外兔肌腱细胞活性和体内退行性变化相关慢性肩袖撕裂修复的影响。

学习规划：

受控实验室研究。

方法：

MSC-Exos 加载贴片是使用动态湿纺系统制造的。在体外研究中，通过用盐水、纤维对齐贴片或 MSC-Exos 加载贴片培养肌腱细胞来评估肌腱细胞的增殖和迁移活性。在体内研究中，建立了兔慢性肩袖撕裂模型并直接修复，纤维对齐补片增强修复（RFPA组），MSC-Exos加载补片增强修复（REPA组）。在手术后 4、8 和 12 周进行组织学和生物力学分析。

结果：

使用动态湿纺系统制造具有内部对齐纤维、松散的微观结构和可靠的初始强度的 MSC-Exos 加载贴片。MSC-Exos 加载贴片显着促进体外肌腱细胞增殖和迁移活动。在体内，与对照组和 RFPA 组相比，REPA 组在术后 8 周和 12 周的肌腱成熟评分显着提高。与对照组和 RFPA 组相比，REPA 组在 4、8 和 12 周时的脂肪浸润显着减少。与对照组和 RFPA 组相比，REPA 组在 12 周时的生物力学性能（包括失效载荷和应力）也显着改善。

结论：

本研究的结果表明，加载 MSC-Exos 的贴片能够通过提供机械支持和最大限度地减少退化来增强慢性肩袖撕裂的修复。

临床相关性：

这项工作支持将生物活性 MSC-Exos 加载到传统设计的肩袖补片中可能比单独的增强补片修复对慢性肩袖撕裂的修复产生更好的效果的想法。