Osteoimmunomodulatory and Mechanobiology-Guided Biomaterials for Craniofacial and Alveolar Bone Regeneration

Craniofacial and alveolar bone regeneration remains a major challenge due to the complex anatomical, mechanical and inflammatory environment of the oral cavity. Traditional biomaterials, largely designed for osteoconduction or osteoinduction, often fail to achieve predictable outcomes in vivo, highlighting the need for strategies that actively regulate the regenerative microenvironment. Recent advances in osteoimmunology and mechanobiology have highlighted the importance of immune responses and mechanical cues in bone regeneration. Redox processes provide an additional perspective for examining how the local microenvironment may modify these responses. In this review, we focus on osteoimmunomodulatory and mechanobiology-guided biomaterial design, discussing redox regulation where it informs immune–mechanical interactions and material function. We highlight key design strategies, including surface engineering, scaffold architecture, bioactive ion release, and immunoregulatory factor delivery, together with selected responsive biomaterials and extracellular vesicle-based delivery systems. Finally, we address the major challenges limiting clinical translation and discuss how material functions may be coordinated with the changing immune and mechanical requirements of repair, while identifying gaps between proposed mechanisms and available evidence.