Manufacturing functional hydrogels for inducing angiogenic–osteogenic coupled progressions in hard tissue repairs: prospects and challenges

In large bone defects, inadequate vascularization within the engineered constructs has been a major challenge in developing clinically impactful products. It is fairly determined that bone tissues and blood vessels are established concurrently throughout tissue repairs after an injury. Thus, the coupling of angiogenesis-osteogenesis is an essential course of action in bone tissue restoration. The manufacture of biomaterial-based scaffolds plays a decisive role in stimulating angiogenic and osteogenic progressions (instruction of neovascularization and bone mineralization). Bone hydrogels with optimal conditions are more efficient at healing bone defects. There has been a remarkable advancement in producing bone substitutes in the tissue engineering area, but the sufficient and timely vascularization of engineered constructs for optimal tissue integration and regeneration is lacking due to mismatch in the scaffold characteristics and new bone tissue reconstruction. Therefore, various key challenges remain to be overcome. A deep understanding of angiogenesis and osteogenesis progressions is required to manufacture bone hydrogels with satisfactory results. The current review briefly discusses the fundamentals of bone tissues, the significance of angiogenesis-osteogenesis progressions and their inducers, the efficacy of biomaterials and composite hydrogel-promoted neo-vasculogenesis (i.e. angiogenesis) and bone mineralization (i.e. osteogenesis), and related challenges, including future research directions.