Osteochondral tissue regeneration using a bilayered composite hydrogel with modulating dual growth factor release kinetics in a rabbit model.

Osteochondral tissue regeneration using a bilayered composite hydrogel with modulating dual growth factor release kinetics in a rabbit model.
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DOI:
10.1016/j.jconrel.2013.03.013
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发表时间:
2013-06-10
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Kasper FK
Kasper FK
中科院分区:
其他
文献类型:
--
作者:
Kim K;Lam J;Lu S;Spicer PP;Lueckgen A;Tabata Y;Wong ME;Jansen JA;Mikos AG;Kasper FK

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研究了生物可降解低聚(聚(乙二醇)富马酸酯)(OPF)复合水凝胶在明胶微粒(GMP)和干细胞群的帮助下用于骨软骨组织再生的生长因子(GF)递送。本研究采用双层OPF复合水凝胶模拟天然骨软骨组织独特的分级结构,研究了具有不同释放动力学的转化生长因子-β3(TGF-β3)和/或胰岛素样生长因子-1(IGF-1)对兔全层骨软骨缺损模型中骨软骨组织再生的影响。研究的四个组包括(i)空白对照(无GF),(ii)单独的GMP负载的IGF-1,(iii)GMP负载的IGF-1和凝胶负载的TGF-β3,以及(iv)OPF复合水凝胶中的GMP负载的IGF-1和GMP负载的TGF-β3。体外释放实验结果表明,GF掺入法可调节TGF-β3的释放动力学。在植入后12周,基于定量组织学评分分析软骨层和软骨下层的组织修复质量。与对照组相比,掺入GF的所有组导致软骨形态的显著改善。当与IGF-1和TGF-β3的双重递送相比时,IGF-1的单次递送显示出在软骨下骨形态以及邻近软骨组织中的软骨细胞和糖胺聚糖量方面的更高评分,与TGF-β3释放动力学无关。结果表明,虽然TGF-β3和IGF-1的双重递送可能不会协同提高工程化组织的质量,但双层复合水凝胶单独递送IGF-1对骨软骨组织修复有积极影响,并有望用于骨软骨组织工程应用。
Biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) composite hydrogels have been investigated for the delivery of growth factors (GFs) with the aid of gelatin microparticles (GMPs) and stem cell populations for osteochondral tissue regeneration. In this study, a bilayered OPF composite hydrogel that mimics the distinctive hierarchical structure of native osteochondral tissue was utilized to investigate the effect of transforming growth factor-β3 (TGF-β3) with varying release kinetics and/or insulin-like growth factor-1 (IGF-1) on osteochondral tissue regeneration in a rabbit full-thickness osteochondral defect model. The four groups investigated included (i) a blank control (no GFs), (ii) GMP-loaded IGF-1 alone, (iii) GMP-loaded IGF-1 and gel-loaded TGF-β3, and (iv) GMP-loaded IGF-1 and GMP-loaded TGF-β3 in OPF composite hydrogels. The results of an in vitro release study demonstrated that TGF-β3 release kinetics could be modulated by the GF incorporation method. At 12 weeks post-implantation, the quality of tissue repair in both chondral and subchondral layers was analyzed based on quantitative histological scoring. All groups incorporating GFs resulted in a significant improvement in cartilage morphology compared to the control. Single delivery of IGF-1 showed higher scores in subchondral bone morphology as well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue when compared to a dual delivery of IGF-1 and TGF-β3, independent of the TGF-β3 release kinetics. The results suggest that although the dual delivery of TGF-β3 and IGF-1 may not synergistically enhance the quality of engineered tissue, the delivery of IGF-1 alone from bilayered composite hydrogels positively affects osteochondral tissue repair and holds promise for osteochondral tissue engineering applications.
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