A crucial component of the musculoskeletal system, the tendon is one of the most commonly injured tissues in the body. In severe cases, the ruptured tendon leads to permanent dysfunction. Although many efforts have been devoted to seeking a safe and efficient treatment for enhancing tendon healing, currently existing treatments have not yet achieved a major clinical improvement. Here, an injectable granular hyaluronic acid (gHA)-hydrogel is engineered to deliver fibromodulin (FMOD)—a bioactive extracellular matrix (ECM) that enhances tenocyte mobility and optimizes the surrounding ECM assembly for tendon healing. The FMOD-releasing granular HA (FMOD/gHA)-hydrogel exhibits unique characteristics that are desired for both patients and health providers, such as permitting a microinvasive application and displaying a burst-to-sustained two-phase release of FMOD, which leads to a prompt FMOD delivery followed by a constant dose-maintaining period. Importantly, the generated FMOD-releasing granular HA hydrogel significantly augmented tendon-healing in a fully-ruptured rat's Achilles tendon model histologically, mechanically, and functionally. Particularly, the breaking strength of the wounded tendon and the gait performance of treated rats returns to the same normal level as the healthy controls. In summary, a novel effective FMOD/gHA-hydrogel is developed in response to the urgent demand for promoting tendon healing.

中文翻译：

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一种用于肌腱愈合和功能恢复的新型可注射纤维调节蛋白释放颗粒水凝胶

作为肌肉骨骼系统的重要组成部分，肌腱是身体中最常受伤的组织之一。在严重的情况下，断裂的肌腱会导致永久性功能障碍。尽管许多努力都致力于寻求一种安全有效的治疗方法来促进肌腱愈合，但目前现有的治疗方法尚未取得重大的临床改善。在这里，一种可注射的颗粒状透明质酸 (gHA)-水凝胶被设计用于递送纤维调节蛋白 (FMOD)——一种具有生物活性的细胞外基质 (ECM)，可增强肌腱细胞的流动性并优化周围的 ECM 组装以促进肌腱愈合。释放 FMOD 的颗粒状 HA (FMOD/gHA)-水凝胶具有独特的特性，是患者和医疗保健提供者都需要的，例如允许微创应用和显示 FMOD 的爆发到持续的两相释放，这导致 FMOD 迅速交付，然后是恒定的剂量维持期。重要的是，生成的释放 FMOD 的颗粒状 HA 水凝胶在组织学、机械和功能上显着增强了完全断裂大鼠跟腱模型的肌腱愈合。特别是，受伤肌腱的断裂强度和治疗大鼠的步态性能恢复到与健康对照组相同的正常水平。总之，为了响应促进肌腱愈合的迫切需求，开发了一种新型有效的 FMOD/gHA-水凝胶。生成的释放 FMOD 的颗粒状 HA 水凝胶在组织学、机械和功能上显着增强了完全断裂大鼠跟腱模型的肌腱愈合。特别是，受伤肌腱的断裂强度和治疗大鼠的步态性能恢复到与健康对照组相同的正常水平。总之，为了响应促进肌腱愈合的迫切需求，开发了一种新型有效的 FMOD/gHA-水凝胶。生成的释放 FMOD 的颗粒状 HA 水凝胶在组织学、机械和功能上显着增强了完全断裂大鼠跟腱模型的肌腱愈合。特别是，受伤肌腱的断裂强度和治疗大鼠的步态性能恢复到与健康对照组相同的正常水平。总之，为了响应促进肌腱愈合的迫切需求，开发了一种新型有效的 FMOD/gHA-水凝胶。