Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair.

Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair.
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双重生长因子从双层,可生物降解的水凝胶复合材料中递送,用于空间引导的骨软骨组织修复。

DOI:
10.1016/j.biomaterials.2014.07.006
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发表时间:
2014-10
期刊:
影响因子:
14
通讯作者:
Kasper, F. Kurtis
Kasper, F. Kurtis
中科院分区:
工程技术1区
文献类型:
--
作者:
Lu, Steven;Lam, Johnny;Trachtenberg, Jordan E.;Lee, Esther J.;Seyednejad, Hajar;van den Beucken, Jeroen J. J. P.;Tabata, Yasuhiko;Wong, Mark E.;Jansen, John A.;Mikos, Antonios G.;Kasper, F. Kurtis

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本工作研究了使用可生物降解的水凝胶复合材料支架,基于大分子单体寡聚(聚(乙二醇)富马酸酯)(OPF),以提供生长因子修复骨软骨组织在兔模型。特别是,双层OPF复合材料用于模拟骨软骨单位的结构层,并将胰岛素样生长因子-1(IGF-1)和骨形态发生蛋白-2(BMP-2)加载到明胶微粒中,并以空间控制的方式嵌入OPF水凝胶基质中。将三种不同的支架形成物植入股骨内侧髁骨软骨缺损中:1)软骨层中的IGF-1,2)软骨下层中的BMP-2,以及3)各自单独层中的IGF-1和BMP-2。在6周和12周时通过组织学评分和显微计算机断层扫描(micro-CT)评价骨软骨修复的数量和质量。虽然在6周时的组织学评分结果显示实验组之间没有差异,但显微CT分析显示,与单独递送IGF-1相比,单独递送BMP-2增加了形成的骨小梁胰岛的数量,这是早期骨形成的指示。在植入后12周,检测到三组之间的软骨修复差异极小。然而,IGF-1和BMP-2的双重递送比IGF-1的单一递送具有更高的软骨下骨修复比例、更大的缺损边缘处的骨生长和更低的骨比表面。这些结果表明,BMP-2的递送增强了软骨下骨形成,并且虽然在所研究的条件下,IGF-1和BMP-2在单独的层中的双重递送没有改善软骨修复,但是它们可以协同地增强软骨下骨形成的程度。总体而言,双层OPF水凝胶复合材料表现出作为空间引导的多种生长因子释放载体用于骨软骨组织修复的潜力。
The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair.
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