Han Ying, Yang Jielai, Zhao Weiwei, Wang Haimang, Sun Yulong, Chen Yuji, Luo Jing, Deng Lianfu, Xu Xiangyang, Cui Wenguo, Zhang Hongyu
State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Bioact Mater. 2021 Mar 26;6(10):3596-3607. doi: 10.1016/j.bioactmat.2021.03.022. eCollection 2021 Oct.
The occurrence of osteoarthritis (OA) is highly associated with the reduced lubrication property of the joint, where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism. In this study, bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel, we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment. Particularly, the lubricating microspheres (GelMA@DMA-MPC) were fabricated by dip coating a self-adhesive polymer (DMA-MPC, synthesized by free radical copolymerization) on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres (GelMA, prepared via microfluidic technology), and encapsulated with an anti-inflammatory drug of diclofenac sodium (DS) to achieve the dual-functional performance. The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres. In addition, the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model, and the biological tests including qRT-PCR, immunofluorescence staining assay, X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA. In summary, the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release, therefore representing a facile and promising technique for the treatment of OA.
骨关节炎（OA）的发生与关节润滑性能降低高度相关，其中关节软骨的进行性和不可逆损伤以及随之而来的炎症反应主导了这一机制。在本研究中，受软骨超润滑特性和贻贝儿茶酚胺化学的启发，我们成功开发了具有增强润滑和可控药物释放功能的可注射水凝胶微球用于OA治疗。具体而言，润滑微球（GelMA@DMA-MPC）是通过将一种自粘性聚合物（DMA-MPC，通过自由基共聚合成）浸涂在光交联甲基丙烯酸明胶水凝胶微球（GelMA，通过微流控技术制备）的表面而制成的，并包裹有双氯芬酸钠（DS）抗炎药物以实现双重功能。摩擦学测试和药物释放测试表明GelMA@DMA-MPC微球具有增强的润滑性和持续的药物释放性能。此外，将功能化微球关节内注射到OA模型大鼠膝关节中，包括qRT-PCR、免疫荧光染色分析、X射线摄影和组织学染色分析在内的生物学测试均表明，生物相容性微球对OA的发展具有显著的治疗效果。总之，本文开发的可注射水凝胶微球极大地改善了润滑性能并实现了局部药物的持续释放，因此是一种治疗OA的简便且有前景 的技术。
