聚乳酸/聚羟基乙酸共聚物支架复合骨形态发生蛋白2基因增强的脂肪干细胞促进软骨缺损修复

摘要

背景:基因增强的组织工程技术可促进种子细胞的增殖和分化,降低异体免疫性,促进血管化,利于骨软骨缺损的修复.目的:观察双层聚乳酸/聚羟基乙酸共聚物支架材料复合慢病毒介导人骨形态发生蛋白2转染的兔脂肪干细胞修复骨软骨缺损的效果.方法:取30只雄性新西兰大白兔,制作双侧股骨关节软骨缺损模型,随机分2组干预,实验组(n=15)于骨缺损处植入骨形态发生蛋白2增强的脂肪干细胞-双层聚乳酸/聚羟基乙酸共聚物支架复合体,结合Mosaicplasty组织工程学技术将自体软骨组织用于填充骨软骨柱间隙;对照组(n=15)植入脂肪干细胞-双层聚乳酸/聚羟基乙酸共聚物支架复合体,结合Mosaicplasty组织工程学技术将自体软骨组织用于填充骨软骨柱间隙;植入后3个月,取缺损处骨修复组织,进行生物力学及蛋白聚糖水平检测;植入后3,6,12个月,取缺损处骨修复组织,进行组织形态学观察.结果与结论:①植入后3个月,实验组压缩模量、蛋白聚糖水平均高于对照组(P＜0.01);②对照组植入后3-12个月的缺损关节表面、颜色、形态及组织学形态均无任何明显变化;与对照组相比,实验组植入后3,6,12个月的缺损关节表面变得光滑,颜色变浅,有透明软骨样组织形成,缺损均有不同程度的愈合,且随着植入后时间的增加,上述变化趋势越来越明显;③结果表明,双层聚乳酸/聚羟基乙酸共聚物支架复合骨形态发生蛋白2基因增强的脂肪干细胞可显著促进骨软骨缺损的修复.%BACKGROUND:Gene-enhanced tissue engineering can promote the proliferation and differentiation of seed cells,reduce allogeneic immunity,promote vascularization,and facilitate the repair of osteochondral defects.OBJECTIVE:To observe the effect of lentivirus-mediated human bone morphogenetic protein-2 (BMP-2) transfected rebbit adipose-derived stem cells (ADSCs) cultured on polylactic acid/polyglycolic acid copolymer scaffold (PLGA) on osteochondral defect repair.METHODS:Thirty male New Zealand rabbits were randomly divided into control group (n=15) and experimental group (n=15).Animal models of bilateral femoral cartilage defects were made in all rabbits.The experimental group was implanted with BMP-2-enhanced ADSCs/PLGA copolymer scaffold,and the control group was implanted with ADSCs/PLGA copolymer scaffold.In both groups,autologous osteochondral mosaicplasty was then performed.After 3 months of implantation,bone tissues at defect region were taken for biomechanical and proteoglycans detection.Histological observation was done at 3,6,12 months after implantation.RESULTS AND CONCLUSION:(1) The compressive modulus and proteoglycan content of the experimental group were significantly higher than those of the control group at 3 months after implantation (P ＜ 0.01).(2) At 3,6 and 12 months after implantation,with the increase of postoperative time,the joint surface in the experimental group became more and more smooth,the color became more and more shallow,and the healing degree of the defect increased to different extent.However,there were no obvious changes in the joint surface,color,morphology and histomorphology in the control group.To conclude,BMP-2-enhanced ADSCs/PLGA copolymer scaffold could significantly promote the repair of osteochondral defects.