Department of Orthopedic Surgery, UConn Health, Farmington, CT, 06030, United States; Institute for Regenerative Engineering, The Raymond Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT, 06030, United States.
Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, School of Dental Medicine, UConn Health, Farmington, CT, 06030, United States.
Int J Biol Macromol. 2018 Jan;106:1159-1165. doi: 10.1016/j.ijbiomac.2017.08.116. Epub 2017 Aug 25.
The study aimed to investigate the localized osteogenic activity of recombinant human bone morphogenetic protein (rhBMP-2), when delivered using enzymatically crosslinkable injectable glycol chitosan hydrogel. A critical sized bilateral calvarial defect model was used wherein one defect was implanted with rhBMP-2 loaded hydrogel (HPP-GC+BMP). The neighboring defect was implanted with an osteoconductive, collagen hydroxyapatite matrix "Healos". The implantation of HPP-GC+BMP led to complete closure of the critical sized defect at 4 weeks post-implantation. The neighboring site implanted with Healos however, did not show any bone formation. The spatial control of rhBMP-2 bioactivity at the cellular level was confirmed by histological and histomorphometric analysis of the calvaria isolated from Col3.6 transgenic animals which can express fluorescence in osteoblast and pre-osteoblast cells. The retained rhBMP-2 in HPPGC+BMP implant was able to localize osteoprogenitor recruitment and osteogenesis, at the implantation site. The results demonstrate the efficacy of HPP-GC hydrogel in minimizing the diffusive loss of rhBMP-2 from the implantation site, compared to the collagen hydroxyapatite scaffold.
该研究旨在探讨局部成骨活性的重组人骨形态发生蛋白（rhBMP-2），当使用可酶交联的注射性乙二醇壳聚糖水凝胶传递。一个关键大小的双侧颅骨缺损模型被用来其中一个缺陷是植入 rhBMP-2 负载水凝胶（HPP-GC+BMP）。相邻的缺陷被植入骨传导性胶原羟基磷灰石基质“Healos”。植入 HPP-GC+BMP 导致临界大小的缺陷在植入后 4 周完全闭合。然而，植入 Healos 的相邻部位没有显示任何骨形成。rhBMP-2 生物活性的空间控制在细胞水平上通过 Col3.6 转基因动物分离的颅骨的组织学和组织形态计量分析得到证实，Col3.6 转基因动物可以在成骨细胞和前成骨细胞中表达荧光。保留在 HPP-GC+BMP 植入物中的 rhBMP-2 能够定位在植入部位的成骨前体细胞募集和骨生成。结果表明，与胶原羟基磷灰石支架相比，HPP-GC 水凝胶在最小化 rhBMP-2 从植入部位的扩散损失方面具有疗效。
