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自体血管内皮祖细胞移植于多孔 PLGA 支架上可构建出用于兔关节透明软骨再生的微环境。

Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.

机构信息

Department of Biomedical Engineering, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan.

出版信息

Osteoarthritis Cartilage. 2013 Oct;21(10):1613-22. doi: 10.1016/j.joca.2013.07.016. Epub 2013 Aug 6.

Abstract

OBJECTIVE

Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery.

METHODS

EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation.

RESULTS

At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-β2 and TGF-β3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th).

CONCLUSION

The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors.

摘要

目的

修复关节软骨在临床上具有挑战性。我们研究了一种简单、有效且具有临床可行性的细胞治疗方法,使用聚(乳酸-共-乙醇酸)(PLGA)支架接种自体内皮祖细胞(EPC),通过一步手术修复兔的全层骨软骨缺损。

方法

通过从兔的少量外周血中纯化获得 EPC,将其接种到高度多孔、生物相容的 PLGA 支架中,即 EPC-PLGA,并植入内侧股骨髁的骨软骨缺损中。22 只兔子随机分为三组:空缺陷组(ED)、PLGA 组或 EPC-PLGA 组。植入后 4 周和 12 周评估缺损部位。

结果

在测试结束时,只有 EPC-PLGA 组显示出具有光滑、透明和整合关节表面的新软骨组织的发育。此外,组织学分析显示出软骨再生的明显差异。在第 4 周时,EPC-PLGA 组 TGF-β2 和 TGF-β3 表达较高,合成糖胺聚糖(GAG)含量较多,修复组织中的骨软骨血管生成程度较高。在第 12 周时,EPC-PLGA 组表现出增强的透明软骨再生,具有正常柱状软骨细胞排列、较高的 SOX9 表达以及更高的 GAG 和胶原 II(COLII)含量。此外,EPC-PLGA 组表现出有组织的骨软骨整合,形成富含血管的结节状骨,并且组织体积和小梁厚度(Tb.Th)的骨体积分数显著更高。

结论

本 EPC-PLGA 细胞输送系统在没有外源性生长因子补充的情况下,为骨软骨再生产生了合适的原位微环境。

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