Department of Orthopaedic Surgery, Korea University Ansan Hospital, Ansan Si, Gyeonggi Do, Korea.
Tissue Eng Part A. 2011 Oct;17(19-20):2389-97. doi: 10.1089/ten.tea.2011.0032. Epub 2011 Jun 17.
The choice of an appropriate carrier and its microarchitectural design is integral in directing bone ingrowth into the defect site and determining its subsequent rate of bone formation and remodeling. We have selected a three-dimensional polycaprolactone (PCL) scaffold with an interconnected honeycomb-like porous structure to provide a conduit for vasculature ingrowth as well as an osteoconductive pathway to guide recruited cells responding to a unique triphasic release of osteoinductive bone morphogenetic proteins (BMP) from these PCL scaffolds. We hypothesize that the use of recombinant human bone morphogenetic protein 2 (rhBMP2)-PCL constructs promotes rapid union and bone regeneration of a large defect. Results of our pilot study on a unilateral 15 mm mid-diaphyseal segmental rabbit ulna defect demonstrated enhanced bone healing with greater amount of bone formation and bridging under plain radiography and microcomputed tomography imaging when compared with an empty PCL and untreated group after 8 weeks postimplantation. Quantitative measurements showed significantly higher bone volume fraction and trabecular thickness, with lower trabecular separation in the rhBMP2-treated groups. Histology evaluation also revealed greater mature bone formation spanning across the entire scaffold region compared with other groups, which showed no bone regeneration within the central defect zone. We highlight that it is the uniqueness of the scaffold having a highly porous network of channels that promoted vascular integration and allowed for cellular infiltration, leading to a discontinuous triphasic BMP2 release profile that mimicked the release profile during natural repair mechanisms in vivo. This study serves as preclinical evidence demonstrating the potential of combining osteoinductive rhBMP2 with our PCL constructs for the repair of large defects in a large animal model.
选择合适的载体及其微观结构设计对于引导骨长入缺损部位并确定随后的骨形成和重塑速率至关重要。我们选择了具有互连通孔蜂窝状多孔结构的三维聚己内酯 (PCL) 支架，为血管长入提供了一个通道，并为募集的细胞提供了一个引导途径，以响应这些 PCL 支架中骨形态发生蛋白 (BMP) 的独特三相释放。我们假设使用重组人骨形态发生蛋白 2 (rhBMP2)-PCL 构建体可促进大缺损的快速愈合和骨再生。在单侧 15 毫米骨干节段性兔尺骨缺损的初步研究中，与植入后 8 周时的空 PCL 和未处理组相比，在普通放射摄影和 microCT 成像下，具有更多骨形成和桥接的增强骨愈合，我们假设使用重组人骨形态发生蛋白 2 (rhBMP2)-PCL 构建体可促进大缺损的快速愈合和骨再生。在单侧 15 毫米骨干节段性兔尺骨缺损的初步研究中，与植入后 8 周时的空 PCL 和未处理组相比，在普通放射摄影和 microCT 成像下，具有更多骨形成和桥接的增强骨愈合，我们假设使用重组人骨形态发生蛋白 2 (rhBMP2)-PCL 构建体可促进大缺损的快速愈合和骨再生。在单侧 15 毫米骨干节段性兔尺骨缺损的初步研究中，与植入后 8 周时的空 PCL 和未处理组相比，在普通放射摄影和 microCT 成像下，具有更多骨形成和桥接的增强骨愈合，结果显示，与空 PCL 和未处理组相比，在植入后 8 周时，普通放射摄影和 microCT 成像显示，骨形成量增加，桥接更多，骨小梁厚度增加，骨小梁分离度降低。定量测量显示，rhBMP2 处理组的骨体积分数和骨小梁厚度明显更高，而其他组在中央缺损区无骨再生。我们强调，正是支架具有高度多孔的通道网络的独特性促进了血管整合，并允许细胞浸润，导致 BMP2 的释放呈不连续的三相释放曲线，模拟了体内自然修复机制中的释放曲线。这项研究为结合有诱导成骨作用的 rhBMP2 和我们的 PCL 构建体来修复大动物模型中的大缺损提供了临床前证据。
