Bioceramic akermanite enhanced vascularization and osteogenic differentiation of human induced pluripotent stem cells in 3D scaffolds in vitro and vivo

Abstract

A growing number of studies suggest that the modulation of cell differentiation by biomaterials is critical for tissue engineering. In previous work, we demonstrated that human induced pluripotent stem cells (iPSCs) are remarkably promising seed cells for bone tissue engineering. In addition, we found that the ionic products of akermanite (Aker) are potential inducers of osteogenic differentiation of iPSCs. Furthermore, composite scaffolds containing polymer and bioceramics have more interesting properties compared to pure bioceramic scaffolds for bone tissue engineering. The characteristic of model biomaterials in bone tissue engineering is their ability to control the osteogenic differentiation of stem cells and simultaneously induce the angiogenesis of endothelia cells. Thus, this study aimed at investigating the effects of poly(lactic-co-glycolic acid)/Aker (PLGA-Aker) composite scaffolds on angiogenic and osteogenic differentiation of human iPSCs in order to optimize the scaffold compositions. The results from Alizarin Red S staining, qRT-PCR analysis of osteogenic genes (BMP2, RUNX2, ALP, COL1 and OCN) and angiogenic genes (VEGF and CD31) demonstrated that PLGA/Aker composite scaffolds containing 10% Aker exhibited the highest stimulatory effects on the osteogenic and angiogenic differentiation of human iPSCs among all scaffolds. After the scaffolds were implanted in nu/nu mice subcutaneous pockets and calvarial defects, H&E staining, BSP immunostaining, qRT-PCR analysis and micro-CT analysis (BMD, BV/TV) indicated that PLGA + 10% Aker scaffolds enhanced the vascularization and osteogenic differentiation of human iPSCs and stimulated the repair of bone defects. Taken together, our work indicated that combining scaffolds containing silicate bioceramic Aker and human iPSCs is a promising approach for the enhancement of bone regeneration.