Strategies for in situ tissue engineering of vascularized bone regeneration (Review)

Numerous physiological processes occur following bone fracture, including inflammatory cell recruitment, vascularization, and callus formation and remodeling. In particular circumstances, such as critical bone defects or osteonecrosis, the regenerative microenvironment is compromised, rendering endogenous stem/progenitor cells incapable of fully manifesting their reparative potential. Consequently, external interventions, such as grafting or augmentation, are frequently necessary. In situ bone tissue engineering (iBTE) employs cell-free scaffolds that possess microenvironmental cues, which, upon implantation, redirect the behavior of endogenous stem/progenitor cells towards a pro-regenerative inflammatory response and reestablish angiogenesis-osteogenesis coupling. This process ultimately results in vascularized bone regeneration (VBR). In this context, a comprehensive review of the current techniques and modalities in VBR-targeted iBTE technology is provided.