Abstract：
Frozen shoulder (FS) is a common and progressive shoulder disorder that causes glenohumeral joint stiffness, characterized by inflammation and fibrosis. The treatment options are quite limited, and the therapeutic response is hindered by the fibrous membrane formed by excessive collagen and the rapid removal by synovial fluid. To address these challenges, we designed a hyaluronic acid/Pluronic F-127 (HP)-based injectable thermosensitive hydrogel as a drug carrier loaded with dexamethasone and collagenase (HPDC). We screened for an optimal HP hydrogel that can sustain drug release for approximately 10 days both in vitro and in vivo. In the meanwhile, we found that HP hydrogel could inhibit the proliferation and diminish the adhesion capacity of rat synovial cells induced by transforming growth factor-β1. Furthermore, using an established immobilization rat model of FS, intra-articular injection of HPDC significantly improved joint range of motion compared to medication alone. Relying on sustained drug release, the accumulated collagen fibers were degraded by collagenase to promote the deep delivery of dexamethasone. These findings showed a positive combined treatment effect of HPDC, providing a novel idea for the comprehensive treatment of FS.
摘要：
冻结肩（FS）是一种常见的进行性肩关节疾病，可导致肱骨关节僵硬，以炎症和纤维化为特征。治疗方案相当有限,治疗反应受到过多胶原蛋白形成的纤维膜和滑液的快速去除的阻碍。为了应对这些挑战，我们设计了一种基于透明质酸/PluronicF-127（HP）的可注射热敏水凝胶作为负载地塞米松和胶原酶（HPDC）的药物载体。我们筛选了可以在体外和体内维持药物释放约10天的最佳HP水凝胶。同时,我们发现HP水凝胶可以抑制转化生长因子β1诱导的大鼠滑膜细胞的增殖和粘附能力。此外，使用建立的FS固定大鼠模型，与单独药物治疗相比,HPDC关节内注射显著改善关节活动范围.依靠持续的药物释放，积累的胶原纤维被胶原酶降解，促进地塞米松的深层递送。这些发现显示了HPDC的积极联合治疗效果，为FS的综合治疗提供了新的思路。
