A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: Controlled release for cartilage tissue engineering

A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: Controlled release for cartilage tissue engineering
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一种在多孔不可降解水凝胶内直接制造负载生长因子的微球的新方法:软骨组织工程的控制释放

DOI:
10.1016/j.jconrel.2011.09.057
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发表时间:
2012-01-10
影响因子:
10.8
通讯作者:
Lowman, Anthony M.
Lowman, Anthony M.
中科院分区:
医学1区
文献类型:
--
作者:
Spiller, Kara L.;Liu, Yu;Lowman, Anthony M.

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由于与天然软骨具有相似的机械性能,基于聚乙烯醇(PVA)的合成水凝胶已被提议用于替代受损的关节软骨,但它们与周围组织完全缺乏整合。在这项研究中,胰岛素样生长因子-1 (IGF-1)是软骨再生的重要生长因子,在双乳液的基础上一步被包裹在可降解的聚乳酸-羟基乙酸(PLGA)微颗粒中,并包裹在PVA水凝胶中。这些水凝胶的IGF-1释放在体外持续超过6周。聚乙二醇酸(PGA)纤维支架包裹水凝胶,植入软骨细胞,皮下植入胸腺小鼠。从细胞外基质成分的含量和力学性能来看,IGF-1的释放促进了水凝胶周围各层软骨的形成,并增加了软骨层与水凝胶之间的结合,这是根据横截面和组织学的大体观察得出的。不含IGF-1的软骨-水凝胶结构的压缩模量为0.07 +/- 0.02 MPa,而含IGF-1的水凝胶结构的压缩模量为0.17-0.2 MPa。尽管IGF-1浓度有一个数量级的差异,但在低浓度和高浓度之间,软骨形成的生化和机械标志物没有差异。这项研究表明,IGF-1的持续释放可以促进组织形成,并指出了影响与周围组织整合的可能策略。(C) 2011 Elsevier b.v.版权所有
Because of similar mechanical properties to native cartilage, synthetic hydrogels based on poly(vinyl alcohol) (PVA) have been proposed for replacement of damaged articular cartilage, but they suffer from a complete lack of integration with surrounding tissue. In this study, insulin-like growth factor-1 (IGF-1), an important growth factor in cartilage regeneration, was encapsulated in degradable poly(lactic-co-glycolic acid) (PLGA) microparticles embedded in the PVA hydrogels in a single step based on a double emulsion. The release of IGF-1 from these hydrogels was sustained over 6 weeks in vitro. Poly(glycolic acid) (PGA) fiber scaffolds were wrapped around the hydrogels, seeded with chondrocytes, and implanted subcutaneously in athymic mice. The release of IGF-1 enhanced cartilage formation in the layers surrounding the hydrogels, in terms of the content of extracellular matrix components and mechanical properties, and increased integration between the cartilage layers and the hydrogels, according to gross observation of the cross-sections and histology. The compressive modulus of the cartilage-hydrogel constructs without IGF-1 was 0.07 +/- 0.02 MPa, compared to 0.17-0.2 MPa for hydrogels that contained IGF-1. The biochemical and mechanical markers of cartilage formation were not different between the low and high concentrations of IGF-1, despite an order of magnitude difference in concentration. This study shows that the sustained release of IGF-1 can enhance tissue formation and points to a possible strategy for effecting integration with surrounding tissue. (C) 2011 Elsevier B. V. All rights reserved.