Polylactic acid/polyglycolic acid copolymer scaffolds carrying bone morphogenetic protein 2 gene enhanced adipose-derived stem cells promote cartilage defect repair

doi:10.3969/j.issn.2095-4344.0056

Abstract

Abstract:

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 rabbit 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.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Bone Morphogenetic Proteins, Stem Cells, Cartilage, Articular, Tissue Engineering

CLC Number:

R318

Ruan Shi-qiang, Deng Jiang, Yan Ling, Huang Wen-liang. Polylactic acid/polyglycolic acid copolymer scaffolds carrying bone morphogenetic protein 2 gene enhanced adipose-derived stem cells promote cartilage defect repair[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(6): 840-845.

Figures/Tables 4

References

[1]秦勇,代志军,吕松岑.关节软骨损伤修复与再生的研究进展[J].医学综述,2013,19(15):2794-2801.

[2]徐杨俊,赵建宁.关节软骨损伤修复的研究进展[J].医学研究生学报,2010,23(8):889-894.

[3]罗飞,许建中.基因增强的骨组织工程研究进展[J].第三军医大学学报,2005,27(16):1702-1704.

[4]阮征,尹庆水,张余,等.关节软骨损伤修复技术的研究与进展[J].临床与病理杂志.2015,35(3):455-461.

[5]陈继营.关节软骨损伤组织工程修复的进展[J].中华关节外科杂志,2013,7(6):744-746.

[6]王君,周琦,邓廉夫,等.PLGA-Fibrin杂合支架构建及与脂肪源性干细胞复合成软骨的研究[J].细胞与分子免疫学杂志,2010, 26(8):758-760.

[7]郭刚,李旭,孙骏,等.自体骨髓基质干细胞辅助Mosaicplasty技术促进骨软骨缺损修复整合[J].中华创伤科杂志, 2006,8(11): 1067-1071.

[8]王跃,杨志明,解慧,等.组织工程化软骨的应力-应变研究[J].生物医学工程学杂志,2001,18(2):169-172.　

[9]王震,梁大川,白洁玉.慢病毒介导的Sox9基因在兔骨髓间充质干细胞的过表达促进软骨损伤修复[J].中国骨伤, 2015,28(5): 433-440.

[10]van den Borne MP,Raijmakers NJ,Vanlauwe J,et al. International Cartilage Repair Society (ICRS) and Oswestry macroscopic cartilage evaluation scores validated for use in Autologous Chondrocyte Implantation (ACI) and microfracture. Osteoarthritis Cartilage. 2007;15(12):1397-1402.

[11]Guo X,Park H,Young S,et al.Repair of osteochondral defects with biodegradable hydrogel composites encapsulating marrow mesenchymal stem cells in a rabbit model.Acta Biomater.2010;6(1):39-47.

[12]李卿,刘伟,夏万尧,等.爱茜蓝法检测组织工程化软骨及软骨细胞中蛋白聚糖的含量[J].中华实验外科杂志,2003,20(1):89.

[13]代岭辉,杜宁.关节软骨损伤生物学修复的研究进展[J].中国骨伤,2009,22(9):721-724.

[14]宋希元,亓建洪.骨软骨移植修复关节软骨缺损的研究进展[J].泰山医学院学报,2004,25(3):244-247.

[15]吕成昱,张海宁,王英振.自体骨髓基质干细胞及可注射藻酸钙凝胶联合Mosaicplasty技术修复山羊膝关节股骨头大面积缺损[J].中国组织工程研究与临床康复,2009,13(47):9253-9256.

[16]Chadli L,Cottalorda J,Delpont M,et al.Autologous osteochondral mosaicplasty in osteochondritis dissecans of the patella in adolescents.Int Orthop.2017;41(1):197-202

[17]Erol MF,Karakoyun O.A new point of view for mosaicplasty in the treatment of focal cartilage defects of knee joint: honeycomb pattern.Springerplus.2016;5(1):1170.

[18]段小军,左镇华,杨柳.细胞移植技术修复关节软骨缺损的临床研究进展[J].中华关节外科杂志,2010,4(1):124-128.

[19]古振,刘芳.脂肪干细胞在骨组织工程中的研究进展[J].组织工程与重建外科杂,2012,2(1):53-55.

[20]Jin MS,Shi S,Zhang Y,et al.Icariin-mediated differentiation of mouse adipose-derived stem cells into cardiomyocytes.Mol Cell Biochem.2010;344(1-2):1-9.

[21]Long JX, Zuk P,Berke GS,et al.Epithelial differentiation of adipose-derived stem cells for laryngeal tissue engineering. Laryngoscope.2010;120(1):125-131.

[22]Gimble J,Guilak F.Adipose-derived adult stem cells: isolation,characterization, and differentiation potential. Cytotherapy.2003;5(5):362-369.

[23]Assoian RK,Grotendorst GR,Miller DM,et al.Cellular transformation by coordinated action of three pep-tide growth factors from human platelets.Nature.1984;309(5971): 804-806.

[24]Han SH,Kim YH,Park MS,et al.Histological and biomechanical properties of regenerated articular cartilage using chondrogenic bone marrow stromal cells with a PLGA scaffold in vivo.J Biomed Mater Res.2008;87(4):850-861.

[25]Karageorgiou V,Kaplan D.Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials.2005;26(27):5474-5491.

[26]刘云忠,牛树茸.同种异体软骨细胞复合PLGA支架修复关节软骨缺损的免疫学观察[J].中国医疗前沿,2010,5(23):26-27.

[27]Julia S,Uwe G,Roger T,et al.Controlled release of gentamicin from cacilum phosphate-poly (lactic acid-coglycolicacid) composite bone cement.Biomaterials.2006;27(9):4239-4249.

[28]蒋宜伟,宋敏,史达,等.关节软骨缺损的基因治疗研究进展[J].颈腰痛杂志,2004,25(1):60-63.

[29]Miyazono K,Maeda S,Imamura T.BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk.Cytokine Growth Factor Rev.2005;16:251-263.

[30]Rosen V.BMP2 signaling in bone development and repair. Cytokine Growth Factor Rev.2009;20(5-6):475-480.

[31]孙骏,侯筱魁,匡勇,等.不同比例骨软骨镶嵌成形术联合基因增强组织工程方法治疗骨软骨缺损[J].中国骨伤, 2011,24(9): 768-744.

[32]郑培惠,魏奉才,晋国营,等.腺病毒介导的骨形态发生蛋白-2基因转染脂肪间充质干细胞的实验研究[J].华西口腔医学杂志, 2006, 24(3):195-198.

[33]邓敏,张楠,唐璐,等.腺病毒介导骨形态发生蛋白2基因转染诱导脂肪间充质干细胞向成骨细胞的定向分化[J].中国组织工程研究与临床康复,2009,13(1):80-83.