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It has been widely reported that chemical, structural or mechanical signals of biomaterials can impact cell behaviors and tissue regeneration, but few studies have investigated the effects of biomaterial signals on cell–cell interactions although communications between cells are critical for tissue regeneration. Our recent studies have shown that chemical signals of bioglass (BG) can stimulate communications in bone marrow stromal cells and endothelial cells, which results in enhanced angiogenesis and osteogenesis. Considering the facts that, in vivo, different biomaterial signals may simultaneously affect cell–cell interactions, in this study, we proposed that combining chemical and structural signals of biomaterials may further improve cell–cell interactions. Results proved that combined structural signals of aligned electrospun nanofibers and chemical signals of BG ionic products could significantly stimulate interactions between co-cultured bone marrow stromal cells and endothelial cells through both of paracrine effects and junctional communications as compared to single type of biomaterial signals. Further study indicated that both chemical signals of BG and structural signals of electrospun nanofibers played important role in stimulating paracrine effects while for improving junctional communication, structural signals of electrospun nanofibers played a more important role than chemical signals of BG, which resulted in enhanced vascularization and osteogenic differentiation in co-cultures. Therefore, applying combined biomaterial signals to activate cell–cell interactions is a promising strategy for enhancing tissue regeneration.

Combined biomaterial signals stimulate communications between bone marrow stromal cell and endothelial cell