Oxygenating biomaterials for fate commitment of stem cells

Oxygenating biomaterials have been developed to alleviate anoxic stress, stimulate vascularization, and improve the engraftment of cellularized implants. However, the effects of oxygen-generating materials on tissue formation have remained largely unknown. Here, we investigate the impact of calcium peroxide (CPO)-based oxygen-generating microparticles (OMPs) on the osteogenic fate of human mesenchymal stem cells (hMSCs) under severely oxygen deficient microenvironment. To this end, CPO was microencapsulated in polycaprolactone to generate OMPs with prolonged oxygen release. Gelatin methacryloyl hydrogels containing osteogenesis-inducing silicate nanoparticles (SH), OMPs (OH), or both (OSH) are engineered to comparatively study their effect on the osteogenic fate of hMSCs. OHs associate with improved osteogenic differentiation under both normoxic and anoxic conditions. Bulk RNAseq analyses suggest that OH under anoxia regulate osteogenic differentiation pathways more strongly than SH or OSH under either anoxia or normoxia. Subcutaneous implantation reveal a stronger host cell invasion in OSH, resulting in increased vasculogenesis. Furthermore, time-dependent expression of different osteogenic factors reveal progressive differentiation of hMSCs in OH, SH, and OSH hydrogels. Our work demonstrates that endowing hydrogels with OMPs can induce, improve, and steer the formation of functional engineered living tissues, which holds potential for numerous biomedical applications, including tissue regeneration and organ replacement therapy.