Advanced biomaterial-based strategies for craniofacial bone regeneration

Craniofacial bone reconstruction presents unique anatomical and functional challenges that differ from those associated with systemic skeletal repair, necessitating specialized regenerative strategies. Despite considerable advancements in bone tissue engineering for addressing complex craniofacial defects, existing approaches often encounter limitations such as insufficient biological activity, mismatched physicochemical properties, and unclear regulatory mechanisms. This review addresses these gaps by systematically examining recent innovations in the utilization of engineered metals, bioceramics, polymers, and emerging biomaterials, emphasizing their enhanced biocompatibility and bioactivity tailored for craniofacial applications. We discuss the integration of these materials with biological insights, focusing on how material-derived physicochemical and biological cues facilitate the coordinated regeneration of mesenchymal stem cells, vascular structures, neural elements, and immune cells within the regenerative microenvironment. Additionally, we summarize preclinical and clinical trials that illustrate the practical applications of these strategies. We propose that future regenerative approaches should emphasize dynamic responsiveness, microenvironmental biomimicry, intelligent monitoring, and multifunctional integration to advance effective therapies for craniofacial bone regeneration.