Department of orthopedics, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, 215000, China.
Institute of Clinical Medicine Research, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, 215000, China.
Small. 2023 Oct;19(40):e2302799. doi: 10.1002/smll.202302799. Epub 2023 Jun 1.
Effective treatments for cartilage defects are currently lacking. Gene delivery using proper delivery systems has shown great potential in cartilage regeneration. However, the inflammatory microenvironment generated by the defected cartilage severely affects the system's delivery efficiency. Therefore, this study reports a silk fibroin microcapsule (SFM) structure based on layer-by-layer self-assembly, in which interleukin-4 (IL-4) is modified on silk by click chemistry and loaded with lysyl oxidase plasmid DNA (LOX pDNA). The silk microcapsules display good biocompatibility and the release rate of genes can be adjusted by controlling the number of self-assembled layers. Moreover, the functionalized SFMs mixed with methacrylated gelatin (GelMA) exhibit good injectability. The IL-4 on the outer layer of the SFM can regulate macrophages to polarize toward the M2 type, thereby promoting cartilage matrix repair and inhibiting inflammation. The LOX pDNA loaded inside can be effectively delivered into cells to promote extracellular matrix generation, significantly promoting cartilage regeneration. The results of this study provide a promising biomaterial for cartilage repair, and this novel silk-based microcapsule delivery system can also provide strategies for the treatment of other diseases.
目前，针对软骨缺陷尚无有效的治疗方法。使用适当的递送系统进行基因递送在软骨再生方面显示出巨大的潜力。然而，受损软骨产生的炎症微环境严重影响了该系统的递送效率。因此，本研究报告了一种基于层层自组装的丝素蛋白微胶囊（SFM）结构，其中通过点击化学将白细胞介素 4（IL-4）修饰在丝素上，并负载赖氨酰氧化酶质粒 DNA（LOX pDNA）。丝素微胶囊具有良好的生物相容性，并且可以通过控制自组装层数来调节基因的释放速率。此外，功能化的 SFM 与甲基丙烯酰化明胶（GelMA）混合具有良好的可注射性。SFM 外层的 IL-4 可以调节巨噬细胞向 M2 型极化，从而促进软骨基质修复并抑制炎症。内部负载的 LOX pDNA 可以有效地递送到细胞中，促进细胞外基质的产生，显著促进软骨再生。本研究结果为软骨修复提供了一种有前途的生物材料，这种新型丝素基微胶囊递送系统也可为治疗其他疾病提供策略。
