Department of Biomedical Engineering, University of California-Davis, Davis, California, USA.
Tissue Eng Part A. 2010 Jan;16(1):127-37. doi: 10.1089/ten.TEA.2009.0255.
The use of composite biomaterials for bone repair capitalizes on the beneficial aspects of individual materials while tailoring the mechanical properties of the composite. We hypothesized that substrate composition would modulate the osteogenic response and secretion of potent trophic factors by human mesenchymal stem cells (hMSCs). Composite scaffolds were prepared by combining nanosized hydroxyapatite (HA) and microspheres formed of poly(lactic-co-glycolic acid) (PLG) at varying ratios between 0:1 and 5:1. Scaffolds were seeded with hMSCs for culture in osteogenic conditions or subcutaneous implantation into nude rats. Compressive moduli increased with HA content in a near-linear fashion. The osteogenic differentiation of hMSCs increased in a dose-dependent manner as determined by alkaline phosphatase activity and osteopontin secretion after 4 weeks of culture. Further, endogenous secretion of vascular endothelial growth factor was sustained at significantly higher levels over 28 days for hMSCs seeded in 2.5:1 and 5:1 HA:PLG scaffolds. Eight weeks after implantation, scaffolds with higher HA:PLG ratios exhibited greater vascularization and more mineralized tissue. These data demonstrate that the mechanical properties, osteogenic differentiation, as well as the timing and duration of trophic factor secretion by hMSCs can be tailored through controlling the composition of the polymer-bioceramic composite.
利用复合生物材料进行骨修复利用了各材料的有益方面，同时调整了复合材料的机械性能。我们假设，基底组成将调节人骨髓间充质干细胞（hMSC）的成骨反应和分泌强效营养因子。通过将纳米级羟基磷灰石（HA）和聚（乳酸-共-乙醇酸）（PLG）微球以 0:1 至 5:1 的不同比例组合来制备复合支架。将 hMSC 接种到支架上，在成骨条件下培养或皮下植入裸鼠。支架的压缩模量随 HA 含量呈近线性增加。通过碱性磷酸酶活性和培养 4 周后骨桥蛋白分泌的测定，hMSC 的成骨分化呈剂量依赖性增加。此外，在接种 2.5:1 和 5:1 HA:PLG 支架的 hMSC 中，内源性血管内皮生长因子的分泌在 28 天内持续保持在更高水平。植入 8 周后，具有较高 HA:PLG 比例的支架表现出更高的血管化和更多矿化组织。这些数据表明，通过控制聚合物-生物陶瓷复合材料的组成，可以调整 hMSC 的机械性能、成骨分化以及营养因子分泌的时间和持续时间。
