Xu Xue, Zhang Yulong, Ha Pin, Chen Yao, Li Chenshuang, Yen Emily, Bai Yuxing, Chen Renji, Wu Benjamin M, Da Lio Andrew, Ting Kang, Soo Chia, Zheng Zhong
Department of Oral and Maxillofacial Plastic and Traumatic Surgery Beijing Stomatological Hospital of Capital Medical University Beijing China.
Division of Plastic and Reconstructive Surgery David Geffen School of Medicine, University of California Los Angeles California USA.
Bioeng Transl Med. 2022 Jul 14;8(1):e10355. doi: 10.1002/btm2.10355. eCollection 2023 Jan.
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.
肌腱是肌肉骨骼系统的关键组成部分，是人体最常受伤的组织之一。在严重情况下，断裂的肌腱会导致永久性功能障碍。尽管人们为寻求安全有效的肌腱愈合治疗方法付出了诸多努力，但目前现有的治疗方法尚未取得重大的临床进展。在此，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），这是一种生物活性细胞外基质（ECM），可增强肌腱细胞的迁移能力，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）水凝胶具有患者和医疗服务提供者都期望的独特特性，例如允许微创应用，并呈现FMOD的突释到缓释的两相释放，这导致FMOD的快速递送，随后是持续的剂量维持期。重要的是，在完全断裂的大鼠跟腱模型中，所制备的释放FMOD的颗粒状HA水凝胶在组织学、力学和功能方面均显著增强了肌腱愈合。特别是，受伤肌腱的断裂强度和治疗大鼠的步态表现恢复到与健康对照组相同的正常水平。总之，针对促进肌腱愈合的迫切需求，开发出了一种新型有效的FMOD/gHA水凝胶。
