Regenerative engineered vascularized bone mediated by calcium peroxide

Abstract One of the main challenges hindering the clinical translation of bone tissue engineering scaffolds is the lack of establishment of functional vasculature. Insufficient vascularization and poor oxygen supply limit cell survival within the constructs resulting in poor osseointegration with the host tissue and eventually leading to inadequate bone regeneration. Inspired by cues from developmental biology, we regenerative engineered a composite matrix by incorporating calcium peroxide (CaO 2 ) into poly(lactide‐co‐glycolide) (PLGA) microsphere‐based matrices and sought to assess whether the delivery of the byproducts of CaO 2 decomposition, namely O 2 , Ca 2+ , and H 2 O 2 could enhance the regeneration of vascularized bone tissue. The composite microspheres were successfully fabricated via the oil‐in‐water emulsion method. The presence and encapsulation of CaO 2 was confirmed using scanning electron microscopy, energy dispersive x‐ray spectroscopy, thermogravimetric analysis, and X‐ray powder diffraction. The microspheres were further heat sintered into three‐dimensional porous scaffolds and characterized for their degradation and release of byproducts. The in vitro cytocompatibility of the matrices and their ability to support osteogenic differentiation was confirmed using human adipose‐derived stem cells. Lastly, an in vivo study was performed in a mouse critical‐sized calvarial defect model to evaluate the capacity of these matrices in supporting vascularized bone regeneration. Results demonstrated that the presence of CaO 2 increased cellularization and biological activity throughout the matrices. There was greater migration of host cells to the interior of the matrices and greater survival and persistence of donor cells after 8 weeks, which in synergy with the composite matrices led to enhanced vascularized bone regeneration.