Hydrogel scaffolds have emerged as instructive microenvironments for craniofacial tissue regeneration, moving beyond passive cell carriers toward platforms that regulate cell fate, vascularization, immune remodeling, and tissue-specific architecture. This review synthesizes hydrogel-associated strategies across dental pulp, periodontal ligament, gingival, bone marrow, jawbone, endothelial, oral mucosal, induced pluripotent stem cell (iPSC), extracellular vesicle (EV), exosome, secretome, and acellular systems. The evidence indicates that craniofacial hydrogel performance is governed by reciprocal interactions among biological source, scaffold composition, matrix mechanics, spatial architecture, mineral or ionic signaling, growth factor delivery, vesicle-mediated communication, and inflammatory niche modulation. Mineralized and ion-releasing hydrogels most consistently supported osteogenesis and bone repair, whereas extracellular matrix (ECM)-mimetic, peptide, collagen, fibrin, gelatin methacryloyl (GelMA), alginate, hyaluronic acid (HA), and chitosan-based systems enabled pulp–dentin, periodontal, peri-implant, oral mucosal, and soft-tissue reconstruction. Responsive, antimicrobial, antioxidant, conductive, and immunomodulatory hydrogels further expanded the field by targeting diseased microenvironments rather than regeneration alone. Despite strong preclinical evidence, translation remains limited by heterogeneity in scaffold formulations, biological sources, analytical endpoints, defect models, and long-term functional validation. Future progress will require standardized characterization, tissue-specific design criteria, clinically relevant large-animal models, scalable cell-free technologies, and integrated assessment of regeneration, immunity, vascularization, innervation, mechanics, and safety.
Omidian et al. (Tue,) studied this question.
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