Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.
Departments of Ophthalmology and Visual Sciences, Cell and Developmental Biology, and Biochemistry and Molecular Biology, SUNY Upstate Medical University, 505 Irving Ave, Syracuse, NY, 13210, USA.
Commun Biol. 2021 Jan 19;4(1):89. doi: 10.1038/s42003-020-01576-y.
Biomimetic bone tissue engineering strategies partially recapitulate development. We recently showed functional restoration of femoral defects using scaffold-free human mesenchymal stem cell (hMSC) condensates featuring localized morphogen presentation with delayed in vivo mechanical loading. Possible effects of construct geometry on healing outcome remain unclear. Here, we hypothesized that localized presentation of transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2 to engineered hMSC tubes mimicking femoral diaphyses induces endochondral ossification, and that TGF-β1 + BMP-2-presenting hMSC tubes enhance defect healing with delayed in vivo loading vs. loosely packed hMSC sheets. Localized morphogen presentation stimulated chondrogenic priming/endochondral differentiation in vitro. Subcutaneously, hMSC tubes formed cartilage templates that underwent bony remodeling. Orthotopically, hMSC tubes stimulated more robust endochondral defect healing vs. hMSC sheets. Tissue resembling normal growth plate was observed with negligible ectopic bone. This study demonstrates interactions between hMSC condensation geometry, morphogen bioavailability, and mechanical cues to recapitulate development for biomimetic bone tissue engineering.
仿生骨组织工程策略部分再现了发育过程。我们最近展示了使用无支架的人类间充质干细胞（hMSC）凝聚物，通过局部呈现形态发生因子并延迟体内机械加载，实现股骨缺损的功能恢复。构建几何形状对愈合结果的可能影响尚不清楚。在这里，我们假设模拟股骨干的工程化 hMSC 管中局部呈现转化生长因子（TGF）-β1 和骨形态发生蛋白（BMP）-2 会诱导软骨内骨化，并且与松散包装的 hMSC 片相比，TGF-β1+BMP-2 呈现的 hMSC 管在延迟体内加载时会增强缺陷愈合。局部形态发生因子呈现刺激体外软骨形成/软骨内分化。皮下，hMSC 管形成软骨模板，经历骨重塑。原位，hMSC 管刺激更强的软骨内缺陷愈合与 hMSC 片。观察到类似于正常生长板的组织，异位骨形成可忽略不计。这项研究表明 hMSC 凝聚几何形状、形态发生因子生物利用度和机械线索之间的相互作用，以模拟发育用于仿生骨组织工程。
