BMP2活性多肽／PLGA复合物植入异位成骨的实验研究

Experimental study on ectopic osteogenesis of a BMP2-derived peptide/PLGA complex

目的用动物实验的方法评价自行研制合成的BMP2活性多肽生物因子与可降解PLGA复合物的异位诱导成骨能力。方法实验分3组。A组：BMP2活性多肽／PLGA复合物组；B组：单纯PLGA组；C组：明胶海绵组。分别于Wistar大鼠背部两侧骶棘肌下包埋植入。术后1、4、8和12周取材。经组织学观察和CT三维成像比较成骨情况，western blot检测Ⅰ型胶原及骨桥蛋白的蛋白表达，了解异位成骨的情况。结果植入块周围初期均表现为急性炎症反应，后期均为淋巴细胞、巨噬细胞浸润为主的非特异性炎症反应。A组植入4周时植入区有软骨生成，8周时有活跃的成骨细胞出现，并有非编织骨结构。12周可见大量新骨形成，有典型的骨小梁新生血管结构。B组和C组12周时仅见纤维组织形成，未见成骨。结论人工合成的BMP2活性多肽体内能启动软骨化骨过程，具有较强的异位诱导成骨能力。有与天然BMP2类似的骨诱导活性，具有广阔的应用前景。

Objective To evaluated the ectopic osteogenetic capacity of synthesis BMP2-derived peptide / polylactide-co-glycolic acid（PLGA） complex by animal experiment. Methods Wistar rats were divided into three groups. The BMP2-derived peptide/PLGA complex was implanted in Group A. Pure PLGA was implanted in Group B, while gelatin sponges were implanted in Group C as control group. The materials were implanted into back muscles of rats. The rats were killed and tissue samples were harvested at 1st, 4th, 8th and 12th week after implantation. Bone formation was detected by X-ray examination. Tissue response was observed histologically. Western blot was used to detect collagen Ⅰ（Col-Ⅰ）and osteopontin （OPN） expression. Results There was acute inflammation in the tissue around all the implants at early stage. Cartilage was found around the materials at 4 weeks after the implantation of BMP2-derived peptide/PLGA complex（Group A）. At 8 weeks, the implanted BMP2-derived peptide/PLGA complex was mostly absorbed while cartilage and osteoblast were found as non-woved bone structur around the implants. At 12 weeks, multiply new bone and woved bone was observed in Group A, some of typical trabecular bone structure. Conclusion PLGA is an ideal scaffold material for bone tissue engineering. BMP2-derived peptide can initiate osteocartilaginea process and induce ectopic osteogenesis more effectively.