制备载BMP-2活性肽新型可降解水凝胶及诱导体内异位成骨的实验研究  

Preparation and ectopic osteogenesis in vivo of scaffold based on new synthetic biodegradable hydrogel loaded with synthetic BMP-2-derived peptide

作　　者：赵晶晶[1] 方真华[1] 黄若昆[1] 肖凯[1] 李静[1] 谢鸣[1] 勘武生[1] 

机构地区：[1]华中科技大学同济医学院附属普爱医院骨科,武汉430034

出　　处：《国际生物医学工程杂志》2013年第3期147-150,I0002,共5页International Journal of Biomedical Engineering

摘　　要：目的将骨形态发生蛋白-2（BMP-2）活性多肽P24复合于聚三甲基碳酸酯-（聚氧乙烯-聚氧丙烯-聚氧乙烯）-聚三甲基碳酸酯（PTMC11-F127-PTMC11）凝胶材料上，测定BMP-2活性多肽P24体外释放曲线是否符合缓释要求。载P24／PTMC11-F127-PTMC11凝胶植人大鼠骶棘肌内，观察异位成骨情况。方法将P24复合于不同质量分数（16％，20％，25％）的PTMC11-F127-PTMC11凝胶材料成形后，二喹啉甲酸（BCA）法测定释放的多肽；将载P24／PTMC11-F127-PTMC11凝胶植于大鼠骶棘肌，行组织学切片HE染色检测。结果根据BCA法检测结果绘制释放曲线分析，质量分数为16％载P24／PTMC11-F127-PTMC11凝胶突释效应较质量分数为20％、25％载P24／PTMC11-F127-PTMC11凝胶突释效应大，后2者在突释效应后释效均匀，可持续释放1个月左右，累积释放97．4％。第4周取材行组织学切片HE染色示-定量不成熟、散在的针状骨小梁组织；第6周可见骨小梁增宽增粗，骨陷窝细胞增多。结论载P24／PTMC11-F127-PTMC11凝胶体外释放曲线符合缓释要求。载P24／PTMC11-F127-PTMC11凝胶在大鼠体内能平稳释放活性多肽，使BMP-2活性多肽在体内能发挥其诱导成骨活性，PTMC11-F127-PTMC11凝胶在体内引起炎症反应少，生物相容性良好，可作为骨形态发生蛋白-2活性多肽合适的载体材料。Objective To prepare P24/PTMC11-F127-PTMC11 hydrogel, to study the in vitro release profile and to observe ectopic bone formation in p24 peptide incorporated PTMC11-F127-PTMC11 hydrogel. Methods Corresponding weight powder of p24 peptide was infunded into tubes of PTMC11-F127-PTMC11 solution with concentrations of 16%, 20% and 25%. Release profiles of P24 peptide in different concentration PTMC11-F127- PTMC11 hydrogel were measured in vitro by BCA assay. PTMC11-F127-PTMC11 hydrogel was implanted into each rat＇s erector muscle of spine, and the implanted gel was detected by hematoxylin and eosin stain （HE）. Results PTMC11-F127-PTMC11 hydrogel showed sustained slow release for the whole process after the initial burst release. With the increase of concentration in PTMCl：F127-PTMCH hydrogel, the initial burst release was reduced significantly. Ectopic bone formation was observed by computed tomography in p24 peptide incorporated PTMC11-F127-PTMC11 hydrogel after four weeks. Bone trabeculae surround the P24/PTMC11-F127-PTMC11 hydrogel was observed at forth week by hematoxylin and eosin stain. The bone trabeculae became thicker from sixth week. Conclusion Delayed release of peptide from the hydrogel was mainly controlled by disintegration of hydrogel and a satisfactory release profile was observed. These results suggest that the p24-1oaded PTMC11-F127-PTMC11 hydrogel remains active of p24 at the implanted site, continuously induce differentiation of osteoblast precursor ceils into osteoblasts, and activate osteoblasts to promote eetopic calcification.

关 键 词：骨组织工程 骨形态发生蛋白-2 水凝胶 自组装 骨诱导 

分 类 号：R943[医药卫生—药剂学]