Chu Tien-Min G, Sargent Peter, Warden Stuart J, Turner Charles H, Stewart Rena L
Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Biomed Sci Instrum. 2006;42:42-7.
Large segmental defects in bones can result from tumor removal, massive trauma, congenital malformation, or non-union fractures. Such defects often are difficult to manage and require multiple-phase surgery to achieve adequate union and function. In this study, we propose a novel design of bone morphogenetic protein 2 (BMP-2) carrier for tissue engineering of segmental defect regeneration. The tube-shaped BMP-2 carrier was fabrication from a poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) composite via casting technique developed in our laboratory. An in vitro evaluation showed that the compressive strength of the carrier decreased about 48% in 12 weeks while maintained a pH in the 6.8-7.4 range. In vivo study was conducted by implanting carriers loaded with 10 microg of BMP-2 in 5 mm rat femur gap model for 15 weeks. X-ray evidence of bridging was first found in the BMP group at 3 weeks. Bridging in all animals (N = 4) in the BMP group was found at 9 weeks. No x-ray evidence of bridging was found in the No BMP group (N = 3). pQCT analysis indicated that the bone mineral density of the callus in the BMP group has reached the level of native femur at 15 weeks after implantation, while the callus in the No BMP group has a bone mineral density at a lower level of 84% to the native femur. Histology analysis shows that a normal fatty bone marrow was restored and mineralized callus formed and bridged the segmental defect.
骨骼中的大段骨缺损可由肿瘤切除、严重创伤、先天性畸形或骨折不愈合引起。此类缺损往往难以处理,需要多阶段手术才能实现充分愈合和功能恢复。在本研究中,我们提出了一种用于节段性缺损再生组织工程的新型骨形态发生蛋白2(BMP-2)载体设计。管状BMP-2载体由聚富马酸丙二醇酯/磷酸三钙(PPF/TCP)复合材料通过我们实验室开发的浇铸技术制成。体外评估表明,载体的抗压强度在12周内下降了约48%,同时pH值保持在6.8-7.4范围内。通过将负载10微克BMP-2的载体植入5毫米大鼠股骨间隙模型中进行15周的体内研究。在BMP组中,3周时首次发现有桥接的X线证据。BMP组所有动物(N = 4)在9周时均发现有桥接。未添加BMP组(N = 3)未发现X线桥接证据。pQCT分析表明,植入后15周,BMP组骨痂的骨密度已达到正常股骨水平,而未添加BMP组骨痂的骨密度较低,为正常股骨的84%。组织学分析显示,恢复了正常的脂肪骨髓,形成了矿化骨痂并桥接了节段性缺损。