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新型分段式聚氨酯/聚乳酸-共-羟基乙酸双层支架局部递送转化生长因子-β1 或骨形态发生蛋白-2 修复软骨。

Cartilage repair by local delivery of transforming growth factor-β1 or bone morphogenetic protein-2 from a novel, segmented polyurethane/polylactic-co-glycolic bilayered scaffold.

机构信息

Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, San Cristóbal de La Laguna 38200, Spain.

出版信息

J Biomed Mater Res A. 2014 Apr;102(4):1110-20. doi: 10.1002/jbma.34769. Epub 2013 Jun 14.

DOI:10.1002/jbma.34769
PMID:23766296
Abstract

This study aimed to analyze the in vitro and in vivo release kinetics and evaluate the grades of repair induced by either the release of 50 ng of transforming growth factor-β1 or 2.5 or 5 μg of bone morphogenetic protein-2 (BMP-2) from a bilayer scaffold of segmented polyurethane/polylactic-co-glycolic (SPU/PLGA) in osteochondral defects, in a rabbit model. The scaffold consisted of a porous, bone-directed PLGA layer, overlaid with a cartilage-directed layer of growth factor (GF)-loaded PLGA microspheres, dispersed in a matrix of SPU. The PLGA porous layer was fabricated by gas foaming. Microspheres were prepared by a double emulsion method. SPU was synthesized by following the two-step method. GF release kinetics were assessed using iodinated ((125)I) GFs. The in vivo release profiles of both GFs fitted to zero-order kinetics, demonstrating a consistently good control of their release rates by SPU. Cartilage-like tissue, characterized by histological analysis, scoring, and immunolabeling of chondrogenic differentiation markers, was observed only after 12 weeks, maintaining integrity up to at least 24 weeks, independently of the GF and the dose of BMP-2. The biocompatibility and the resulting good quality, hyaline repair cartilage convert this system into a promising candidate for future applications in osteochondral lesions.

摘要

本研究旨在分析转化生长因子-β1(TGF-β1)或骨形态发生蛋白-2(BMP-2)从双层多孔聚己内酯/聚乳酸共聚物(SPU/PLGA)支架中的体外和体内释放动力学,并评估其在兔骨软骨缺损模型中诱导修复的程度。支架由多孔的骨导向 PLGA 层和生长因子(GF)负载的 PLGA 微球组成的软骨导向层组成,分散在 SPU 基质中。PLGA 多孔层通过气体发泡法制备。微球通过复乳法制备。SPU 通过两步法合成。使用碘标记的(125)GF 评估 GF 释放动力学。两种 GF 的体内释放曲线均符合零级动力学,表明 SPU 能很好地控制其释放速度。只有在 12 周后才观察到软骨样组织,通过组织学分析、评分和软骨分化标志物的免疫标记进行评估,在至少 24 周内保持完整性,与 GF 和 BMP-2 的剂量无关。该系统具有良好的生物相容性和修复质量,产生透明软骨,使其成为未来骨软骨病变应用的有前途的候选者。

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