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BMP-12 过表达间充质干细胞负载 3D 打印 PLGA 支架在兔肩袖修复中的应用。

The application of BMP-12-overexpressing mesenchymal stem cells loaded 3D-printed PLGA scaffolds in rabbit rotator cuff repair.

机构信息

Department of Sports Medicine, Peking University Shenzhen Hospital, 518000 Shenzhen, China.

First Clinical Medical College of Anhui Medical University, 230000 Hefei, China.

出版信息

Int J Biol Macromol. 2019 Oct 1;138:79-88. doi: 10.1016/j.ijbiomac.2019.07.041. Epub 2019 Jul 8.

Abstract

This study investigates if the application of bone marrow-derived mesenchymal stem cells (BM-MSCs) loaded 3D-printed scaffolds could improve rotator cuff repair. The polylactic-co-glycolic acid (PLGA) scaffolds were fabricated by 3D print technology. Rabbit BM-MSCs were transfected with a recombinant adenovirus encoding bone morphogenic protein 12 (BMP-12). The effect of BM-MSCs loaded PLGA scaffolds on tendon-bone healing was assessed by biomechanical testing and histological analysis in a rabbit rotator cuff repair model. We found that the PLGA scaffolds had good biocompatible and biodegradable property. Overexpression of BMP-12 increased the mRNA and protein expression of tenogenic genes in BM-MSCs cultured with DMEM medium and seeded in PLGA scaffolds. When BMP-12-overexpressing BM-MSCs-loaded PLGA scaffolds were implanted into the injured rabbit supraspinatus tendon-bone junctions, the tendon-bone healing was improved. Our results suggest that application of BMP-12 overexpressing BM-MSCs loaded 3D-printed PLGA scaffolds promote the healing of tendon-bone interface, improve collagen organization and increase fibrocartilage in the rabbit rotor cuff repair. Rotator cuff regeneration achieved by BMP-12-overexpressing BM-MSCs-loaded PLGA scaffolds may represent a novel approach for the management of rotator cuff defect.

摘要

本研究旨在探讨骨髓间充质干细胞(BM-MSCs)负载三维打印支架是否能改善肩袖修复。采用 3D 打印技术制备聚乳酸-共-羟基乙酸(PLGA)支架。兔 BM-MSCs 转染携带骨形态发生蛋白 12(BMP-12)的重组腺病毒。通过生物力学测试和兔肩袖修复模型的组织学分析评估负载 BM-MSCs 的 PLGA 支架对腱骨愈合的影响。我们发现 PLGA 支架具有良好的生物相容性和可降解性。BMP-12 的过表达增加了 DMEM 培养基中培养的 BM-MSCs 和接种在 PLGA 支架中的腱性基因的 mRNA 和蛋白表达。当 BMP-12 过表达的 BM-MSCs 负载的 PLGA 支架植入受伤的兔冈上肌腱-骨结合处时,腱骨愈合得到改善。我们的结果表明,应用 BMP-12 过表达的 BM-MSCs 负载的 3D 打印 PLGA 支架可促进腱骨界面愈合,改善胶原组织,增加兔肩袖修复中的纤维软骨。BMP-12 过表达的 BM-MSCs 负载 PLGA 支架的肩袖再生可能代表了一种治疗肩袖缺损的新方法。

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