Sharmin Farzana, Adams Douglas, Pensak Michael, Dukas Alexander, Lieberman Jay, Khan Yusuf
Department of Materials Science and Engineering, University of Connecticut, Storrs, Connecticut.
Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut.
J Biomed Mater Res A. 2015 Sep;103(9):2847-54. doi: 10.1002/jbm.a.35435. Epub 2015 Feb 26.
According to 5- and 10-year clinical follow-up studies large-scale bone allografts have a high failure rate, largely due to poor allograft incorporation with adjacent bone and subsequent poor remodeling. The goal of this study was to develop a methodology to deliver growth factors from large-scale bone allografts in a temporally controlled manner. Intact long bone allografts were coated with a micron-scale thick layer of degradable polymer that maintained inherent pore structures and acted as a delivery vehicle for bone morphogenetic protein-2 and vascular endothelial growth factor. VEGF was loaded onto the surface of the polymer to produce rapid release, to encourage initial vascularization at the defect site, while BMP-2 was encapsulated within the polymer layer to promote a more sustained release, to encourage bone formation over time. Release kinetics from factor-loaded polymer-coated allografts show an early burst release of VEGF over the first 7 days followed by a more sustained release of BMP-2 over the second and third week. In vitro cell studies using human mesenchymal stem cells confirm the bioactivity of the released BMP-2. In-vivo results show robust bone formation over the first 8 weeks of healing in femoral segmental defects in rats implanted with BMP-2 loaded polymer-coated allografts. A microscale thin coating of degradable polymer on a large-scale bone allograft provides temporal control over the delivery of growth factor loaded onto one allograft, while maintaining its microscale pore structure. Enhancing the incorporation and subsequent remodeling of allografts would reduce the incidence of allograft failure over time, and potentially speed healing at the earliest stages after implantation.
根据5年和10年的临床随访研究，大规模骨移植的失败率很高，这主要是由于异体骨与相邻骨的结合不佳以及随后的重塑不良。本研究的目的是开发一种方法，以时间可控的方式从大规模骨移植中递送生长因子。完整的长骨移植体被涂上一层微米级厚的可降解聚合物，该聚合物保持了固有的孔隙结构，并作为骨形态发生蛋白-2和血管内皮生长因子的递送载体。将血管内皮生长因子（VEGF）加载到聚合物表面以实现快速释放，促进缺损部位的初始血管化，而骨形态发生蛋白-2（BMP-2）则被包裹在聚合物层内以促进更持续的释放，随着时间的推移促进骨形成。负载因子的聚合物涂层移植体的释放动力学显示，VEGF在最初7天有早期爆发式释放，随后在第二和第三周BMP-2有更持续的释放。使用人间充质干细胞的体外细胞研究证实了释放的BMP-2的生物活性。体内结果显示，在植入负载BMP-2的聚合物涂层移植体的大鼠股骨节段性缺损愈合的前8周内有强劲的骨形成。在大规模骨移植体上进行微米级薄涂层的可降解聚合物，可对负载在一个移植体上的生长因子的递送进行时间控制，同时保持其微米级孔隙结构。增强移植体的结合及随后的重塑将随着时间的推移降低移植体失败的发生率，并有可能在植入后的最早阶段加快愈合。
