Pore size regulates mesenchymal stem cell response to Bioglass-loaded composite scaffolds

Composite scaffolds fabricated from synthetic polymers and bioceramics such as bioactive glasses are promising alternatives to autogenous bone grafts for treatment of bone defects. Compared to other bioceramics, we previously demonstrated that bioactive glass (Bioglass 45S®, BG) further enhances the osteogenic program of bone-forming osteoblasts when incorporated into poly(lactide-co-glycolide) (PLG) macroporous scaffolds. However, cell response is dependent on parameters beyond scaffold composition including pore size and bioceramic availability to cells. We hypothesized that the osteogenic potential of human mesenchymal stem/stromal cells (MSCs) seeded on BG composite scaffolds was dependent upon pore diameter. Composite BG scaffolds were formed with three pore diameters - 125-300 μm, 300-500 μm, and 500-850 μm - by controlling porogen size. To determine the contribution of pore size to composite scaffold osteogenic potential, we characterized the biophysical properties, bioceramic distribution within the scaffold, and the osteogenic response of MSCs. All composite scaffolds were approximately 2-fold stiffer than the PLG control, and scaffolds with 500-850 μm pore diameters induced the greatest osteogenic response. The enhanced response of MSCs to scaffolds fabricated with large pores resulted from increased presentation of Bioglass along pore surfaces, enabling increased interaction between the cells and bioceramic. These data indicate that cellular behavior is dependent upon both pore size and material composition, confirming that the role of pore size should be considered in the development of new materials designed for bone repair.