Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0363, USA.
J Mech Behav Biomed Mater. 2012 Jul;11:123-31. doi: 10.1016/j.jmbbm.2011.11.007. Epub 2011 Nov 28.
The use of tissue grafting for the repair of large bone defects has numerous limitations including donor site morbidity and the risk of disease transmission. These limitations have prompted research efforts to investigate the effects of combining biomaterial scaffolds with biochemical cues to augment bone repair. The goal of this study was to use a critically-sized rat femoral segmental defect model to investigate the efficacy of a delivery system consisting of an electrospun polycaprolactone (PCL) nanofiber mesh tube with a silk fibroin hydrogel for local recombinant bone morphogenetic protein 2 (BMP-2) delivery. Bilateral 8 mm segmental femoral defects were formed in 13-week-old Sprague Dawley rats. Perforated electrospun PCL nanofiber mesh tubes were fitted into the adjacent native bone such that the lumen of the tubes contained the defect (Kolambkar et al., 2011b). Silk hydrogels with or without BMP-2 were injected into the defect. Bone regeneration was longitudinally assessed using 2D X-ray radiography and 3D microcomputed topography (μCT). Following sacrifice at 12 weeks after surgery, the extracted femurs were either subjected to biomechanical testing or assigned for histology. The results demonstrated that silk was an effective carrier for BMP-2. Compared to the delivery system without BMP-2, the delivery system that contained BMP-2 resulted in more bone formation (p<0.05) at 4, 8, 12 weeks after surgery. Biomechanical properties were also significantly improved in the presence of BMP-2 (p<0.05) and were comparable to age-matched intact femurs. Histological evaluation of the defect region indicated that the silk hydrogel has been completely degraded by the end of the study. Based on these results, we conclude that a BMP-2 delivery system consisting of an electrospun PCL nanofiber mesh tube with a silk hydrogel presents an effective strategy for functional repair of large bone defects.
组织移植修复大骨缺损有许多局限性，包括供体部位发病率和疾病传播的风险。这些局限性促使研究人员努力研究将生物材料支架与生化线索结合起来以增强骨修复的效果。本研究的目的是使用大鼠股骨节段性缺损模型来研究由静电纺聚己内酯（PCL）纳米纤维网管和丝素水凝胶组成的输送系统用于局部重组骨形态发生蛋白 2（BMP-2）输送的功效。在 13 周龄的 Sprague Dawley 大鼠中形成双侧 8mm 节段性股骨缺损。将穿孔的静电纺 PCL 纳米纤维网管安装到相邻的天然骨中，使得管腔包含缺损（Kolambkar 等人，2011b）。将含有或不含有 BMP-2 的丝素水凝胶注入缺损部位。使用二维 X 射线射线照相术和三维微计算机断层扫描（μCT）对骨再生进行纵向评估。手术后 12 周处死时，提取的股骨要么进行生物力学测试，要么进行组织学评估。结果表明丝素是 BMP-2 的有效载体。与不含 BMP-2 的输送系统相比，含有 BMP-2 的输送系统在手术后 4、8、12 周时可导致更多的骨形成（p<0.05）。在存在 BMP-2 的情况下，生物力学性能也得到了显著改善（p<0.05），并且与同龄的完整股骨相当。对缺损区域的组织学评估表明，丝素水凝胶在研究结束时已完全降解。基于这些结果，我们得出结论，由静电纺 PCL 纳米纤维网管和丝素水凝胶组成的 BMP-2 输送系统为大骨缺损的功能性修复提供了一种有效的策略。
