Kuang Yiwen, Hua Bingqiang, Ye Xiaoping, Zhao Yujin, Yu Meng, Liu Xianwen
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China.
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Mater Today Bio. 2025 Jul 15;33:102103. doi: 10.1016/j.mtbio.2025.102103. eCollection 2025 Aug.
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by variable degrees of inflammatory cartilage degeneration and subchondral bone erosion. Current clinical treatments mainly focus on symptomatic relief, such as pain management, and no disease-modifying osteoarthritis (OA) drugs (DMOADs) have been approved for widespread clinical use by regulatory bodies. Although fibroblast growth factor (FGF18) has shown great potential to be DMOADs in clinical trials for OA treatment by stimulating cartilage regeneration, its efficacy of inducing anabolic responses in articular cartilage is significantly limited by inflammatory conditions. In this study, we delivered FGF18 using an innovative hydrogel that underwent responsive degradation in the reactive oxygen species (ROS)-enriched TMJOA sites, continuously delivering the cartilage-repairing FGF18 and consuming ROS, further counteracting the limitation of inflammatory factors on cartilage repair ability of FGF18, thereby hindering the progression of TMJOA. This is the first attempt to hinder TMJOA progression with FGF18, and has demonstrated the dual function of hydrogel in reducing inflammation levels and promoting cartilage repair in TMJOA environment. This discovery addresses the limitations of short retention time of FGF18 in clinical applications, and also provides a new strategy for improving articular cartilage repair by overcoming the inflammatory environment.
颞下颌关节骨关节炎（TMJOA）是一种退行性疾病，其特征为不同程度的炎症性软骨退变和软骨下骨侵蚀。目前的临床治疗主要集中在症状缓解，如疼痛管理，且尚无疾病修饰性骨关节炎（OA）药物（DMOADs）获监管机构批准广泛用于临床。尽管成纤维细胞生长因子（FGF18）在OA治疗的临床试验中通过刺激软骨再生显示出作为DMOADs的巨大潜力，但其在关节软骨中诱导合成代谢反应的功效因炎症状态而受到显著限制。在本研究中，我们使用一种创新水凝胶递送FGF18，该水凝胶在富含活性氧（ROS）的TMJOA部位发生响应性降解，持续递送修复软骨的FGF18并消耗ROS，进一步抵消炎症因子对FGF18软骨修复能力的限制，从而阻碍TMJOA的进展。这是首次尝试用FGF18阻碍TMJOA进展，并证明了水凝胶在降低TMJOA环境中炎症水平和促进软骨修复方面的双重功能。这一发现解决了FGF18在临床应用中保留时间短的局限性，也为通过克服炎症环境改善关节软骨修复提供了新策略。
