Files
Abstract
This dissertation demonstrates that engineered collagen-based microenvironments can be designed to improve craniofacial bone regeneration by integrating matrix mechanics, biomimetic mineralization, and self-assembled vasculature. Increased matrix density alone is sufficient to rapidly activate osteogenic mechanotransduction pathways, but this early advantage does not translate to improved long term bone regeneration, highlighting the need to balance mechanical reinforcement with biological accessibility. Incorporating nanoscale mineralization enhances early mechanosensing and significantly accelerates bone repair in vivo, with mineralization influencing both the extent and spatial pattern of regeneration as well as showing sex-specific healing responses. Finally, pre-vascularized, decellularized mineralized scaffolds support robust bone regeneration comparable to autologous grafts, demonstrating the potential for scalable, off-the-shelf graft alternatives.