Lei Lei, Wang Shuo, Wu Honghui, Ju Wei, Peng Jian, Qahtan Anwar Saeed Ahmed, Chen Chen, Lu Yanqin, Peng Jieying, Zhang Xing, Nie Hemin
Department of Stomatology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
J Biomed Mater Res A. 2015 Jan;103(1):252-61. doi: 10.1002/jbm.a.35168. Epub 2014 Apr 2.
In the modern design, most delivery systems for bone regeneration focus on a single growth factor (GF) or a simple mixture of multiple GFs, overlooking the coordination of proliferation and osteogenesis induced by various factors. In this study, core-shell microspheres with poly-l-lactide core-poly(lactic-co-glycolic acid) shell were fabricated, and two GFs, basic fibroblast growth factor 2 (FGF-2) and bone morphogenetic protein 2 (BMP-2) were encapsulated into the core or/and shell. The effects of different release patterns (parallel or sequential manners) of FGF-2 and BMP-2 from these core-shell microspheres on the osteogenic differentiation of low-population density human mesenchymal stem cells (hMSCs) were investigated and the temporal organization of GF release was optimized. In vitro experiments suggested that induction of osteogenic differentiation of low-population density hMSCs by the sequential delivery of FGF-2 followed by BMP-2 from the core-shell microspheres (group S2) was much more efficient than that by the parallel release of the two factors from uniform microspheres (group U). The osteogenic induction by the sequential delivery of BMP-2 followed by FGF-2 from core-shell microspheres (group S1) was even worse than that from microspheres loaded with BMP-2 in both core and shell (group B), although comparable to the cases of parallel delivery of dual GFs (group P). This study showed the advantages of group S2 microspheres in inducing osteogenic differentiation of low-population density hMSCs and the necessity of time sequence studies in tissue engineering while multiple GFs are involved.
在现代设计中，大多数用于骨再生的递送系统都聚焦于单一生长因子（GF）或多种GF的简单混合物，而忽略了各种因子诱导的增殖与成骨之间的协同作用。在本研究中，制备了具有聚左旋丙交酯核-聚（乳酸-乙醇酸）壳的核壳微球，并将两种生长因子，即碱性成纤维细胞生长因子2（FGF-2）和骨形态发生蛋白2（BMP-2）封装到核层或/和壳层中。研究了FGF-2和BMP-2从这些核壳微球中不同释放模式（平行或顺序方式）对低细胞密度人骨髓间充质干细胞（hMSCs）成骨分化的影响，并优化了生长因子释放的时间组织。体外实验表明，核壳微球按顺序先释放FGF-2后释放BMP-2（S2组）诱导低细胞密度hMSCs成骨分化的效率远高于两种因子从均匀微球中平行释放（U组）。核壳微球按顺序先释放BMP-2后释放FGF-2（S1组）的成骨诱导效果甚至比核层和壳层都负载BMP-2的微球（B组）更差，尽管与双生长因子平行释放的情况（P组）相当。本研究显示了S2组微球在诱导低细胞密度hMSCs成骨分化方面的优势，以及在组织工程中涉及多种生长因子时进行时间序列研究的必要性。
