Department of Orthopaedics, Union Hospital, Tongji, Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
ACS Biomater Sci Eng. 2023 Mar 13;9(3):1672-1681. doi: 10.1021/acsbiomaterials.2c01144. Epub 2023 Feb 16.
Osteoarthritis (OA) is an inflammatory disease accompanied by synovial joint inflammation, and IL-36 plays an important role in this process. Local application of IL-36 receptor antagonist (IL-36Ra) can effectively control the inflammatory response, thereby protecting cartilage and slowing down the development of OA. However, its application is limited by the fact that it is rapidly metabolized locally. We designed and prepared a temperature-sensitive poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel (IL-36Ra@Gel) system carrying IL-36Ra and evaluated its basic physicochemical characteristics. The drug release curve of IL-36Ra@Gel indicated that this system could slowly release the drug over a longer period. Furthermore, degradation experiments showed that it could be largely degraded from the body within 1 month. The biocompatibility-related results showed that it had no significant effect on cell proliferation compared to the control group. In addition, the expression of MMP-13 and ADAMTS-5 was lower in IL-36Ra@Gel-treated chondrocytes than in the control group, and the opposite results appeared in aggrecan and collagen X. After 8 weeks of treatment with IL-36Ra@Gel by joint cavity injection, HE and Safranin O/Fast green staining showed that the degree of cartilage tissue destruction in the IL-36Ra@Gel-treated group was less than those in other groups. Meanwhile, the joints of mice in the IL-36Ra@Gel group had the most intact cartilage surface, the smallest thickness of cartilage erosion, and the lowest OARSI and Mankins score among all groups. Consequently, the combination of IL-36Ra and PLGA-PLEG-PLGA temperature-sensitive hydrogels can greatly improve the therapeutic effect and prolong the drug duration time, thus effectively delaying the progression of degenerative changes in OA, providing a new feasible nonsurgical treatment for OA.
骨关节炎（OA）是一种炎症性疾病，伴有滑膜关节炎症，IL-36 在这一过程中发挥重要作用。局部应用 IL-36 受体拮抗剂（IL-36Ra）可以有效控制炎症反应，从而保护软骨并减缓 OA 的发展。然而，其应用受到局部快速代谢的限制。我们设计并制备了一种携带 IL-36Ra 的温敏聚（乳酸-共-羟基乙酸）-聚（乙二醇）-聚（乳酸-共-羟基乙酸）（PLGA-PEG-PLGA）水凝胶（IL-36Ra@Gel）系统，并对其基本理化特性进行了评价。IL-36Ra@Gel 的药物释放曲线表明，该系统可以在较长时间内缓慢释放药物。此外，降解实验表明，它可以在 1 个月内从体内大量降解。与对照组相比，生物相容性相关结果表明其对细胞增殖没有显著影响。此外，在 IL-36Ra@Gel 处理的软骨细胞中，MMP-13 和 ADAMTS-5 的表达低于对照组，而在聚集蛋白聚糖和胶原 X 中则出现相反的结果。关节腔内注射 IL-36Ra@Gel 8 周后，HE 和 Safranin O/Fast green 染色显示，IL-36Ra@Gel 处理组的软骨组织破坏程度低于其他组。同时，IL-36Ra@Gel 组的关节软骨表面最完整，软骨侵蚀厚度最小，OARSI 和 Mankins 评分最低。因此，IL-36Ra 与 PLGA-PLEG-PLGA 温敏水凝胶的结合可以极大地提高治疗效果并延长药物作用时间，从而有效延缓 OA 退行性变化的进展，为 OA 提供一种新的可行的非手术治疗方法。
