Bone Tissue Engineering Center, Department of Biomedical Engineering and Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15219, USA.
Biomed Mater. 2012 Aug;7(4):045008. doi: 10.1088/1748-6041/7/4/045008. Epub 2012 Jun 1.
The purposes of this study were to determine the pharmacokinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) from a polyurethane (PUR)-based porous scaffold and to determine the biological responses of human mesenchymal stem cells (hMSCs) to the rhBMP-2 released from those scaffolds. The rhBMP-2 was incorporated into the PUR three-dimensional (3D) porous scaffolds and release profiles were determined using enzyme-linked immunosorbent assay. The bioactivity of the rhBMP-2 containing releasates was determined using hMSCs and compared with exogenous rhBMP-2. Release of rhBMP-2 from PUR-based systems was bi-phasic and characterized by an initial burst followed by a sustained release for up to 21 days. Expression of alkaline phosphatase activity by hMSCs treated with the rhBMP-2 releasates was significantly greater than the cells alone (control) throughout the time periods. Furthermore, after 14 days of culture, the hMSCs cultured with rhBMP-2 releasate had a greater amount of mineralization compared to exogenous rhBMP-2. Overall, the rhBMP-2 release from the PUR-based scaffolds was sustained for 21 days and the releasates appeared to be bioactive and promoted earlier osteogenic differentiation and mineralization of hMSCs than the exogenous rhBMP-2.
本研究旨在确定源自聚氨酯(PUR)多孔支架的重组人骨形态发生蛋白-2(rhBMP-2)的药代动力学,并确定人间充质干细胞(hMSC)对rhBMP-2 从这些支架中释放的生物反应。rhBMP-2 被掺入 PUR 三维(3D)多孔支架中,并使用酶联免疫吸附测定法确定释放曲线。使用 hMSC 测定含有 rhBMP-2 的释放物的生物活性,并与外源性 rhBMP-2 进行比较。rhBMP-2 从 PUR 基系统中的释放呈双相特征,最初是爆发性释放,然后持续释放长达 21 天。用 rhBMP-2 释放物处理的 hMSC 表达碱性磷酸酶活性在整个时间段内均明显大于单独的细胞(对照)。此外,在培养 14 天后,与外源性 rhBMP-2 相比,用 rhBMP-2 释放物培养的 hMSC 具有更多的矿化。总体而言,rhBMP-2 从 PUR 基支架中的释放可持续 21 天,并且释放物似乎具有生物活性,并促进了 hMSC 的早期成骨分化和矿化,优于外源性 rhBMP-2。