Department of Chemical Engineering and Pharmaceutical Technology, and ‡Institute of Biomedical Technologies (ITB), Center for Biomedical Research of the Canary Islands, University of La Laguna , 38200 La Laguna, Spain.
Biomacromolecules. 2014 Apr 14;15(4):1311-22. doi: 10.1021/bm401854d. Epub 2014 Mar 11.
A sandwich-like system, fabricated with electrospun, poly(lactic-co-glycolic-acid) (PLGA) membranes incorporating either human recombinant bone morphogenetic protein 2 (BMP-2) enriched microspheres, rat bone marrow mesenchymal stem cells (rMSC), or rMSC with their Smurf1 (SMAD ubiquitin regulatory factor-1) expression knocked down by means of siRNA (rMSC573) at varying densities was evaluated in a rat calvarial, critical-size defect. The behavior of four membrane varieties, fabricated with different PLGA copolymers, was initially studied in rMSC cultures to decide on optimal membrane degradation and cell proliferation and differentiation characteristics. PLGA75:25 provided the most stable structure, and favored the cell environment. Radiological and histological analyses indicated bone repair in animals treated with the PLGA75:25 bioactivated systems. We found no synergist interaction between BMP-2 and rMSC 8 to 12 weeks postimplantation. By contrast, synergistic defect repair of around 85% was detected after 8 weeks of combined BMP-2 and rMSC573 treatment.
采用静电纺丝技术制备了一种三明治样系统，该系统由聚（乳酸-共-乙醇酸）（PLGA）膜组成，其中包含富含人重组骨形态发生蛋白 2（BMP-2）的微球、大鼠骨髓间充质干细胞（rMSC）或通过 siRNA 敲低 Smurf1（SMAD 泛素调节因子-1）表达的 rMSC（rMSC573），以不同的密度进行复合。该系统在大鼠颅骨临界尺寸缺损模型中进行了评估。首先在 rMSC 培养物中研究了四种不同 PLGA 共聚物制备的膜的特性，以确定最佳的膜降解和细胞增殖及分化特性。PLGA75:25 提供了最稳定的结构，有利于细胞环境。影像学和组织学分析表明，接受 PLGA75:25 生物激活系统治疗的动物的骨修复情况良好。我们没有发现 BMP-2 和 rMSC 之间在植入后 8 至 12 周时有协同作用。相比之下，在联合使用 BMP-2 和 rMSC573 治疗 8 周后，检测到约 85%的协同缺陷修复。
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