Xu Zhuoming, Ma Jun, Hu Hanyin, Liu Jintao, Yang Haiyang, Chen Jiayi, Xu Hongwei, Wang Xinyu, Luo Huanhuan, Chen Gang
Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Orthopaedics, Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
Front Bioeng Biotechnol. 2025 Jan 28;13:1540592. doi: 10.3389/fbioe.2025.1540592. eCollection 2025.
Osteoarthritis (OA) is a degenerative disease of the joints characterized by cartilage degradation and synovial inflammation. Due to the complex pathogenesis of OA, multifaceted therapies that modulate inflammatory and immune microenvironmental disturbances while promoting cartilage regeneration are key to control the progression of OA.
Herein, a multifunctional nanoparticle (DIC/Mg-PDA NPs) was constructed successfully by the metal chelation effect between Mg and catecholamine bond from dopamine, followed by the amidation with diclofenac (DIC), which was then prepared into an injectable hydrogel microsphere (DIC/Mg-PDA@HM) with immune-regulating and cartilage-repairing abilities through microfluidic technology for the treatment of osteoarthritis.
The sustained release of Mg from the composite hydrogel microspheres achieved inflammatory immune regulation by converting macrophages from M1 to M2 and promoted cartilage regeneration through the differentiation of BMSCs. Moreover, the enhanced release of DIC and polydopamine (PDA) effectively downregulated inflammatory factors, and finally achieved OA therapy. In addition, MRI and tissue section staining of OA model proved the significant efficacy of the hydrogel microspheres on OA. In conclusion, these novel hydrogel microspheres demonstrated a promising prospect for multidisciplinary repairing of OA.
骨关节炎（OA）是一种关节退行性疾病，其特征在于软骨降解和滑膜炎症。由于OA的发病机制复杂，在调节炎症和免疫微环境紊乱的同时促进软骨再生的多方面治疗是控制OA进展的关键。
在此，通过镁与多巴胺的儿茶酚胺键之间的金属螯合作用，成功构建了一种多功能纳米颗粒（DIC/Mg-PDA NPs），随后用双氯芬酸（DIC）进行酰胺化，然后通过微流控技术将其制备成具有免疫调节和软骨修复能力的可注射水凝胶微球（DIC/Mg-PDA@HM）用于治疗骨关节炎。
复合水凝胶微球中镁的持续释放通过将巨噬细胞从M1型转变为M2型实现了炎症免疫调节，并通过骨髓间充质干细胞的分化促进了软骨再生。此外，双氯芬酸（DIC）和聚多巴胺（PDA）的增强释放有效地下调了炎症因子，最终实现了OA治疗。此外，OA模型的MRI和组织切片染色证明了水凝胶微球对OA具有显著疗效。总之，这些新型水凝胶微球在OA的多学科修复方面显示出广阔的前景。
