Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital East Campus, Shanghai University of Medicine and Health Sciences, Shanghai, People's Republic of China; Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109833. doi: 10.1016/j.msec.2019.109833. Epub 2019 May 30.
The different lineage-specific biological properties of articular cartilage and subchondral bone present a great challenge in the construction of bi-lineage scaffolds for simultaneous osteochondral regeneration. To overcome this challenge, strontium incorporated calcium silicate (Sr-CS) ceramic was prepared for bi-lineage formation of scaffolds in this study. The positive result of Sr-CS in the regeneration of osteochondral defects was first proven by its improved effect on the osteogenesis and chondrogenesis induction of mesenchymal stem cells (MSCs). After that, scaffold-mediated macrophage polarization between classically activated inflammatory macrophages (termed M1Ф) and alternatively activated inflammatory macrophages (termed M2Ф) was assayed to investigate whether the incorporation of Sr into calcium silicate could alter host-to-scaffold immune response. Furthermore, the interactions between Sr-CS pretreated macrophages and MSCs differentiation were performed to prove the enhancement effect of suppressed inflammatory response on osteogenesis and chondrogenesis. In vivo transplantation showed that the Sr-CS scaffolds distinctly improved the regeneration of cartilage and subchondral bone, as compared to the calcium silicate scaffolds. On the one hand, the mechanism attributes to enhancement of strontium on the osteogenic and chondrogenic differentiation of MSCs. On the other hand, the reason can partially be attributed to suppressed synovial inflammatory response, which has improved effects on enhancement of osteogenesis and chondrogenesis. These findings suggest that monophasic Sr-CS scaffolds with a bi-lineage conducive property and an inflammatory response regulatory property represents a viable strategy for simultaneous regeneration of osteochondral defects.
关节软骨和软骨下骨的不同谱系特异性生物学特性在构建用于同时进行骨软骨再生的双谱系支架方面提出了巨大挑战。为了克服这一挑战，本研究中制备了掺入锶的硅酸钙（Sr-CS）陶瓷，以用于支架的双谱系形成。Sr-CS 在骨软骨缺损再生中的积极作用首先通过其对间充质干细胞（MSCs）成骨和成软骨诱导的改善作用得到证实。之后，通过检测支架介导的巨噬细胞向经典激活的炎性巨噬细胞（称为 M1Ф）和选择性激活的炎性巨噬细胞（称为 M2Ф）的极化来研究将 Sr 掺入硅酸钙是否可以改变宿主对支架的免疫反应。此外，还进行了 Sr-CS 预处理巨噬细胞与 MSC 分化之间的相互作用，以证明抑制炎性反应对成骨和成软骨的增强作用。体内移植表明，与硅酸钙支架相比，Sr-CS 支架明显改善了软骨和软骨下骨的再生。一方面，其机制归因于 Sr 对 MSCs 的成骨和成软骨分化的增强作用。另一方面，部分原因可归因于抑制性滑膜炎症反应，该反应对增强成骨和成软骨有积极作用。这些发现表明，具有双谱系促进特性和炎症反应调节特性的单相 Sr-CS 支架是同时再生骨软骨缺损的可行策略。
