Bioactive materials have now raised considerable attention for the treatment of osteoarthritis (OA), such as knee OA, rheumatoid OA, and temporomandibular joint (TMJ) OA. TMJ-OA is a common disease associated with an imbalance of cartilage regeneration, tissue inflammation, and disability in mouth movement. Recently, biological materials or molecules have been developed for TMJ-OA therapy; however, ideal treatment is still lacking. In this study, we used the combination of a human platelet rich plasma with hyaluronic acid (hPRP/HA) for TMJ-OA therapy to perform a clinical trial in dish to humans. Herein, hPRP was prepared, and the hPRP/HA combined concentration was optimized by MTT assay. For the clinical trial in dish, pro-inflammatory-induced in-vitro and in-vivo mimic 3D TMJ-OA models were created, and proliferation, gene expression, alcian blue staining, and IHC were used to evaluate chondrocyte regeneration. For the animal studies, complete Freund’s adjuvant (CFA) was used to induce the TMJ-OA rat model, and condyle and disc regeneration were investigated through MRI. For the clinical trial in humans, 12 patients with TMJ-OA who had disc displacement and pain were enrolled. The disc displacement and pain at baseline and six months were measured by MRI, and clinical assessment, respectively. Combined hPRP/HA treatment ameliorated the proinflammatory-induced TMJ-OA model and promoted chondrocyte proliferation by activating SOX9, collagen type I/II, and aggrecan. TMJ-OA pathology–related inflammatory factors were efficiently downregulated with hPRP/HA treatment. Moreover, condylar cartilage was regenerated by hPRP/HA treatment in a proinflammatory-induced 3D neocartilage TMJ-OA-like model. During the animal studies, hPRP/HA treatment strongly repaired the condyle and disc in a CFA-induced TMJ-OA rat model. Furthermore, we performed a clinical trial in humans, and the MRI data demonstrated that after 6 months of treatment, hPRP/HA regenerated the condylar cartilage, reduced disc displacement, alleviated pain, and increased the maximum mouth opening (MMO). Overall, clinical trials in dish to human results revealed that hPRP/HA promoted cartilage regeneration, inhibited inflammation, reduced pain, and increased joint function in TMJ-OA. Conclusively, this study highlighted the therapeutic potential of the hPRP and HA combination for TMJ-OA therapy, with detailed evidence from bench to bedside. Trial registration Taipei Medical University Hospital (TMU-JIRB No. N201711041). Registered 24 November 2017. https://tmujcrc.tmu.edu.tw/inquiry_general.php .

中文翻译：

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含透明质酸的血小板衍生生物材料可缓解颞下颌关节骨关节炎：从培养皿到人体的临床试验

生物活性材料目前在治疗骨关节炎（OA）方面引起了相当大的关注，例如膝关节OA、类风湿性OA和颞下颌关节（TMJ）OA。TMJ-OA 是一种常见疾病，与软骨再生失衡、组织炎症和口腔运动障碍相关。最近，已经开发出用于TMJ-OA治疗的生物材料或分子；然而，仍缺乏理想的治疗方法。在这项研究中，我们使用富含人类血小板的血浆与透明质酸 (hPRP/HA) 的组合进行 TMJ-OA 治疗，在人体培养皿中进行了临床试验。在此，制备hPRP，并通过MTT测定优化hPRP/HA组合浓度。对于培养皿中的临床试验，创建了促炎诱导的体外和体内模拟 3D TMJ-OA 模型，并使用增殖、基因表达、阿尔新蓝染色和 IHC 来评估软骨细胞再生。在动物研究中，使用完全弗氏佐剂（CFA）诱导TMJ-OA大鼠模型，并通过MRI研究髁突和椎间盘再生。在人体临床试验中，招募了 12 名患有椎间盘移位和疼痛的 TMJ-OA 患者。分别通过 MRI 和临床评估测量基线和六个月时的椎间盘移位和疼痛。hPRP/HA 联合治疗可改善促炎诱导的 TMJ-OA 模型，并通过激活 SOX9、I/II 型胶原蛋白和聚集蛋白聚糖促进软骨细胞增殖。hPRP/HA 治疗可有效下调 TMJ-OA 病理相关炎症因子。此外，在促炎诱导的 3D 新软骨 TMJ-OA 样模型中，通过 hPRP/HA 治疗，髁软骨得以再生。在动物研究中，hPRP/HA 治疗可有效修复 CFA 诱导的 TMJ-OA 大鼠模型中的髁突和椎间盘。此外，我们在人体中进行了一项临床试验，MRI数据表明，治疗6个月后，hPRP/HA使髁突软骨再生，减少椎间盘移位，减轻疼痛，并增加最大张口度（MMO）。总体而言，人体培养皿临床试验结果表明，hPRP/HA 促进软骨再生、抑制炎症、减轻疼痛并增强 TMJ-OA 的关节功能。总之，这项研究强调了 hPRP 和 HA 组合治疗 TMJ-OA 的治疗潜力，并提供了从实验室到临床的详细证据。试验注册台北医学大学附设医院（TMU-JIRB No. N201711041）。2017 年 11 月 24 日注册。 https://tmujcrc.tmu.edu.tw/inquiry_general.php 。