Zhai Dong, Chen Lei, Chen Yu, Zhu Yufang, Xiao Yin, Wu Chengtie
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China. zhuyufang @mail.sic.ac.cn.
Biomater Sci. 2020 Aug 21;8(16):4521-4534. doi: 10.1039/d0bm00450b. Epub 2020 Jul 10.
Articular cartilage lesions occur frequently but unfortunately the damaged cartilage has a very limited intrinsic repair capacity. Since the cartilage damage can cause sterile inflammation, the effects of inflammation on cartilage repair should be well understood for precise treatment. Our previous study showed that bioceramics play an important role in cartilage regeneration. However, it is unclear how the immune microenvironment induced by bioactive ceramics influences cartilage regeneration. In this study, we applied the model bioactive ceramic lithium calcium silicate (LiCaSiO, LCS) to prepare scaffolds and explore whether LCS scaffolds could promote cartilage maturation by regulating macrophage polarization. It was found that LCS induced the shifting of macrophages to anti-inflammatory M2 phenotype by downregulating the expressions of inflammatory genes TNFα, IL-6 and IL-1β and promoting the expression of IL-10 genes. The conditioned medium from LCS-treated macrophages promoted the proliferation, migration and maturation of chondrocytes. In a chondrocyte and macrophage co-culture system, LCS scaffolds induced chondrocyte maturation. These results demonstrated that LCS significantly promoted chondrocyte maturation by immunomodulating the M2 macrophage polarization. Hence, LCS scaffolds have great potential in cartilage repair, indicating that bioceramics may be used in cartilage regeneration due to their immunomodulatory effects on macrophages.
关节软骨损伤很常见,但不幸的是,受损软骨的内在修复能力非常有限。由于软骨损伤会引发无菌性炎症,因此为了进行精准治疗,需要深入了解炎症对软骨修复的影响。我们之前的研究表明,生物陶瓷在软骨再生中发挥着重要作用。然而,尚不清楚生物活性陶瓷诱导的免疫微环境如何影响软骨再生。在本研究中,我们应用模型生物活性陶瓷硅酸锂钙(LiCaSiO,LCS)制备支架,并探讨LCS支架是否能通过调节巨噬细胞极化来促进软骨成熟。研究发现,LCS通过下调炎症基因TNFα、IL-6和IL-1β的表达并促进IL-10基因的表达,诱导巨噬细胞向抗炎M2表型转变。LCS处理的巨噬细胞的条件培养基促进了软骨细胞的增殖、迁移和成熟。在软骨细胞与巨噬细胞共培养系统中,LCS支架诱导软骨细胞成熟。这些结果表明,LCS通过免疫调节M2巨噬细胞极化显著促进了软骨细胞成熟。因此,LCS支架在软骨修复方面具有巨大潜力,这表明生物陶瓷因其对巨噬细胞的免疫调节作用,可能用于软骨再生。