Lupu-Haber Yael, Pinkas Oded, Boehm Stefanie, Scheper Thomas, Kasper Cornelia, Machluf Marcelle
Faculty of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel, 32000.
Biomed Microdevices. 2013 Dec;15(6):1055-66. doi: 10.1007/s10544-013-9797-1.
Bone tissue engineering is an alternative approach to bone grafts. In our study we aim to develop a composite scaffold for bone regeneration made of doped zirconium oxide (ZrO2) conjugated with poly(lactic-co-glycolic acid) (PLGA) particles for the delivery of growth factors. In this composite, the PLGA microspheres are designed to release a crucial growth factor for bone formation, bone morphogenetic protein-2 (BMP2). We found that by changing the polymer's molecular weight and composition, we could control microsphere loading, release and size. The BMP2 released from PLGA microspheres retained its biological activity and increased osteoblastic marker expression in human mesenchymal stem cells (hMSCs). Uncapped PLGA microspheres were conjugated to ZrO2 scaffolds using carbodiimide chemistry, and the composite scaffold was shown to support hMSCs growth. We also demonstrated that human umbilical vein endothelial cells (HUVECs) can be co-cultured with hMSCs on the ZrO2 scaffold for future vascularization of the scaffold. The ZrO2 composite scaffold could serve as a bone substitute for bone grafting applications with the added ability of releasing different growth factors needed for bone regeneration.
骨组织工程是一种替代骨移植的方法。在我们的研究中,我们旨在开发一种用于骨再生的复合支架,该支架由掺杂的氧化锆(ZrO2)与聚乳酸-乙醇酸共聚物(PLGA)颗粒共轭而成,用于生长因子的递送。在这种复合材料中,PLGA微球被设计用于释放对骨形成至关重要的生长因子——骨形态发生蛋白-2(BMP2)。我们发现,通过改变聚合物的分子量和组成,可以控制微球的负载、释放和尺寸。从PLGA微球释放的BMP2保留了其生物活性,并增加了人间充质干细胞(hMSCs)中骨细胞标志物的表达。使用碳二亚胺化学方法将未封端的PLGA微球与ZrO2支架共轭,结果表明该复合支架能够支持hMSCs的生长。我们还证明,人脐静脉内皮细胞(HUVECs)可以与hMSCs在ZrO2支架上共培养,以便将来实现支架的血管化。ZrO2复合支架可以作为骨移植应用的骨替代物,并具有释放骨再生所需不同生长因子的额外能力。