Wang Qiang, Zhang Yanxia, Li Bin, Chen Liang
Department of Orthopaedic Surgery, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P. R. China.
J Mater Chem B. 2017 Sep 7;5(33):6963-6972. doi: 10.1039/c7tb00949f. Epub 2017 Aug 14.
The controlled co-release of osteoinductive and angiogenic factors is an efficient approach to promote vascularized bone regeneration, and a suitable controlled release system can largely reduce the usage of these factors to avoid cost and safety problems. In this study, a cell-free vascularized bone tissue engineering system based on a silk fibroin (SF)/nanohydroxyapatite (nHAp) scaffold was developed, in which very low doses of osteoinductive and angiogenic factors, bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), were embedded and released in a controlled manner to facilitate bone formation and vascularization, respectively. BMP-2 and VEGF were adsorbed onto SF microspheres (diameter of 1.5 ± 0.3 μm) that were prepared using a co-flow capillary device, and these microspheres were subsequently incorporated within the SF/nHAp scaffolds to provide controlled release. BMP-2 and VEGF were incorporated into SF microspheres via chemical covalent bonding and physical adsorption, respectively, leading to their controlled and sustained release from the SF/nHAp scaffolds. The rapid initial release of VEGF mimicked its expression at the early bone healing stage and promoted angiogenesis, and the relatively slow and sustained release of BMP-2 facilitated osteogenic differentiation both in vitro and in vivo, and the bone completely bridged the rat calvarial defects after 12 weeks of implantation. Overall, our findings suggest that the controlled dual release of very low doses of BMP-2 (300 ng per scaffold) and VEGF (20 ng per scaffold) from SF/nHAp scaffolds results in a synergistic effect on vascularized bone regeneration; this controlled release system can largely reduce the usage of BMP-2 as compared to other systems.
骨诱导和血管生成因子的可控共释放是促进血管化骨再生的有效方法，合适的控释系统可以大大减少这些因子的用量，避免成本和安全问题。在本研究中，开发了一种基于丝素蛋白（SF）/纳米羟基磷灰石（nHAp）支架的无细胞血管化骨组织工程系统，其中极低剂量的骨诱导和血管生成因子，即骨形态发生蛋白-2（BMP-2）和血管内皮生长因子（VEGF），以可控方式包埋并释放，分别促进骨形成和血管化。BMP-2和VEGF吸附到使用共流毛细管装置制备的SF微球（直径为1.5±0.3μm）上，随后将这些微球掺入SF/nHAp支架中以实现控释。BMP-2和VEGF分别通过化学共价键合和物理吸附掺入SF微球中，从而使其从SF/nHAp支架中可控且持续地释放。VEGF的快速初始释放模拟了其在早期骨愈合阶段的表达并促进血管生成，而BMP-2相对缓慢且持续的释放促进了体外和体内的成骨分化，植入12周后骨完全桥接大鼠颅骨缺损。总体而言，我们的研究结果表明，从SF/nHAp支架中可控地双重释放极低剂量的BMP-2（每个支架300 ng）和VEGF（每个支架20 ng）对血管化骨再生产生协同作用；与其他系统相比，这种控释系统可以大大减少BMP-2的用量。
