Osteogenesis and Trophic Factor Secretion are Influenced by the Composition of Hydroxyapatite/Poly(Lactide-Co-Glycolide) Composite Scaffolds
Osteogenesis and Trophic Factor Secretion are Influenced by the Composition of Hydroxyapatite/Poly(Lactide-Co-Glycolide) Composite Scaffolds
复制标题
DOI：
10.1089/ten.tea.2009.0255
复制
发表时间：
2010-01-01
影响因子：
4.1
通讯作者：
Leach, J. Kent
中科院分区：
文献类型：
--
作者：
He, Jiawei;Genetos, Damian C.;Leach, J. Kent
使用复合生物材料进行骨修复利用了单个材料的有益方面，同时定制了复合材料的机械性能。我们假设基质成分会调节人间充质干细胞（hMSCs）的成骨反应和强效营养因子的分泌。将纳米羟基磷灰石（HA）和聚（乳酸-羟基乙酸）（PLG）微球以0：1至5：1的不同比例组合，制备复合支架。将hMSCs接种于支架上，用于成骨条件下的培养或皮下植入裸鼠体内。压缩模量随HA含量以近线性方式增加。培养4周后，碱性磷酸酶活性和骨桥蛋白分泌测定显示hMSCs的成骨分化呈剂量依赖性增加。此外，对于接种在2.5：1和5：1 HA：PLG支架中的hMSC，血管内皮生长因子的内源性分泌在28天内维持在显著更高的水平。植入8周后，具有较高HA：PLG比率的支架表现出更大的血管化和更多的矿化组织。这些数据表明，可以通过控制聚合物-生物陶瓷复合物的组成来定制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。
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.