School of Dentistry, The University of Queensland, Brisbane, Queensland, 4006, Australia.
School of Dentistry, The University of Queensland, Brisbane, Queensland, 4006, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove Campus, Brisbane, 4006, Australia.
Biochem Biophys Res Commun. 2019 May 14;512(4):889-895. doi: 10.1016/j.bbrc.2019.03.132. Epub 2019 Mar 28.
Traditional treatments for bone repair with allografts and autografts are limited by the source of bone substitutes. Bone tissue engineering via a cell-based bone tissue scaffold is a new strategy for treatment against large bone defects with many advantages, such as the accessibility of biomaterials, good biocompatibility and osteoconductivity; however, the inflammatory immune response is still an issue that impacts osteogenesis. Sphingosine 1-phosphate (S1P) is a cell-derived sphingolipid that can mediate cell proliferation, immunoregulation and bone regeneration. We hypothesised that coating S1P on a β-Tricalcium phosphate (β-TCP) scaffold could regulate the immune response and increase osteogenesis. We tested the immunoregulation capability on macrophages and the osteogenic capability on rat bone marrow stromal cells of the coated scaffolds, which showed good biocompatibility. Additionally, the coated scaffolds exhibited dose-dependent inhibition of inflammatory-related gene expression. A high concentration of S1P (0.5 μM) upregulated osteogenic-related gene expression of OPN, OCN and RUNX2, which also significantly increased the alkaline phosphatase activity, as compared with the control group. In conclusion, S1P coated β-TCP scaffold could inhibit inflammation and promote bone regeneration.
传统的同种异体骨和自体骨修复方法受到骨替代物来源的限制。基于细胞的骨组织支架的骨组织工程是治疗大骨缺损的一种新策略，具有生物材料易得、良好的生物相容性和骨诱导性等优点；然而，炎症免疫反应仍然是影响成骨的一个问题。1-磷酸鞘氨醇（S1P）是一种细胞衍生的鞘脂，可以介导细胞增殖、免疫调节和骨再生。我们假设在 β-磷酸三钙（β-TCP）支架上涂覆 S1P 可以调节免疫反应并增加成骨作用。我们测试了涂层支架对巨噬细胞的免疫调节能力和对大鼠骨髓基质细胞的成骨能力，结果显示其具有良好的生物相容性。此外，涂层支架表现出对炎症相关基因表达的剂量依赖性抑制作用。与对照组相比，高浓度 S1P（0.5 μM）上调了 OPN、OCN 和 RUNX2 的成骨相关基因表达，同时还显著增加了碱性磷酸酶活性。总之，S1P 涂层的 β-TCP 支架可以抑制炎症并促进骨再生。
