Department of Chemical and Biomolecular Engineering, Rice University, MS-362, P.O. Box 1892, Houston, TX 77251-1892, USA.
Acta Biomater. 2010 Jan;6(1):39-47. doi: 10.1016/j.actbio.2009.07.041. Epub 2009 Aug 4.
This work investigated the delivery of marrow mesenchymal stem cells (MSCs), with or without the growth factor transforming growth factor-beta1 (TGF-beta1), from biodegradable hydrogel composites on the repair of osteochondral defects in a rabbit model. Three formulations of oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel composites containing gelatin microparticles (GMPs) and MSCs were implanted in osteochondral defects, including (i) OPF/GMP hydrogel composites; (ii) OPF/GMP hydrogel composites encapsulating MSCs; and (iii) OPF hydrogel composites containing TGF-beta1-loaded GMPs and MSCs. At 12weeks, the quality of new tissue formed in chondral and subchondral regions of defects was evaluated based on subjective and quantitative histological analysis. OPF hydrogel composites were partially degraded and the defects were filled with newly formed tissue at 12weeks with no sign of persistent inflammation. With the implantation of scaffolds alone, newly formed chondral tissue had an appearance of hyaline cartilage with zonal organization and intense staining for glycosaminoglycans, while in the subchondral region hypertrophic cartilage with some extent of bone formation was often observed. The addition of MSCs, especially with TGF-beta1-loaded GMPs, facilitated subchondral bone formation, as evidenced by more trabecular bone appearance. However, the delivery of MSCs with or without TGF-beta1 at the dosage investigated did not improve cartilage morphology. While OPF-based hydrogel composites supported osteochondral tissue generation, further investigations are necessary to elucidate the effects of MSC seeding density and differentiation stage on new tissue formation and regeneration.
本研究旨在探讨骨髓间充质干细胞（MSCs）在骨软骨缺损修复中的应用，包括其在可生物降解水凝胶复合材料中的递送，以及添加或不添加生长因子转化生长因子-β1（TGF-β1）的情况。在兔模型中，将三种含明胶微球（GMPs）和 MSCs 的聚（乙二醇琥珀酸酯）（OPF）水凝胶复合材料制剂（i）OPF/GMP 水凝胶复合材料；（ii）OPF/GMP 水凝胶复合材料包封 MSCs；（iii）含 TGF-β1 负载 GMPs 和 MSCs 的 OPF 水凝胶复合材料植入骨软骨缺损中。在 12 周时，根据主观和定量组织学分析评估软骨和软骨下区域缺陷中新组织的形成质量。OPF 水凝胶复合材料在 12 周时部分降解，缺陷被新形成的组织填充，无持续炎症的迹象。单独植入支架时，新形成的软骨组织具有透明软骨的外观，具有带区组织和糖胺聚糖的强烈染色，而在软骨下区域，通常观察到具有一定程度骨形成的肥大软骨。添加 MSCs，特别是负载 TGF-β1 的 GMPs，促进了软骨下骨形成，表现为更多的小梁骨外观。然而，在所研究的剂量下，无论是否添加 TGF-β1，MSC 的递送都不能改善软骨形态。虽然 OPF 基水凝胶复合材料支持骨软骨组织的生成，但需要进一步研究以阐明 MSC 接种密度和分化阶段对新组织形成和再生的影响。
