PDF(Pubmed)
Abstract：
Osteoarthritis (OA) is a degenerative disease potentially exacerbated due to inflammation, cartilage degeneration, and increased friction. Both mesenchymal stem cells (MSCs) and pro-inflammatory macrophages play important roles in OA. A promising approach to treating OA is to modify multi-functional hydrogel microspheres to target the OA microenvironment and structure. Arginyl-glycyl-aspartic acid (RGD) is a peptide widely used in bioengineering owing to its cell adhesion properties, which can recruit BMSCs and macrophages. We developed TLC-R, a microsphere loaded with TGF-β1-containing liposomes. The recruitment effect of TLC-R on macrophages and BMSCs was verified by in vitro experiments, along with its function of promoting chondrogenic differentiation of BMSCs. And we evaluated the effect of TLC-R in balancing OA metabolism in vitro and in vivo. When TLC-R was co-cultured with BMSCs and lipopolysaccharide (LPS)-treated macrophages, it showed the ability to recruit both cells in substantial numbers. As the microspheres degraded, TGF-β1 and chondroitin sulfate (ChS) were released to promote chondrogenic differentiation of the recruited BMSCs, modulate chondrocyte metabolism and inhibit inflammation induced by the macrophages. Furthermore, in vivo analysis showed that TLC-R restored the narrowed space, reduced osteophyte volume, and improved cartilage metabolic homeostasis in OA rats. Altogether, TLC-R provides a comprehensive and novel solution for OA treatment by dual-modulating inflammatory and chondrocyte metabolism.
摘要：
骨关节炎（OA）是一种退行性疾病，可能由于炎症而加剧，软骨退化，增加摩擦。间充质干细胞（MSCs）和促炎巨噬细胞在OA中起重要作用。治疗OA的一种有希望的方法是修饰多功能水凝胶微球以靶向OA微环境和结构。精氨酰-甘氨酰-天冬氨酸（RGD）是一种由于其细胞粘附特性而广泛用于生物工程的肽，可以招募BMSCs和巨噬细胞。我们开发了TLC-R,载有含有TGF-β1的脂质体的微球。通过体外实验验证了TLC-R对巨噬细胞和BMSCs的募集作用,并具有促进BMSCs向软骨分化的作用。并且我们评估了TLC-R在平衡体外和体内OA代谢中的作用。当TLC-R与BMSCs和脂多糖（LPS）处理的巨噬细胞共培养时，它显示了大量募集两个细胞的能力。随着微球的降解，TGF-β1和硫酸软骨素（ChS）被释放以促进招募的BMSCs的软骨分化，调节软骨细胞代谢并抑制巨噬细胞诱导的炎症。此外，体内分析表明，TLC-R恢复了狭窄的空间，骨赘体积减少，改善OA大鼠软骨代谢稳态。总之,TLC-R通过双重调节炎症和软骨细胞代谢为OA治疗提供了一种全面而新颖的解决方案。
