Immunomodulatory Biomaterials for Craniomaxillofacial, Periodontal, and Pulp-Dentin Tissue Regeneration

Oral, craniofacial, and dental tissues differ in developmental origins, healing capacity, and immunological niche, and these differences complicate functional regeneration. Healing across the craniomaxillofacial, periodontal, and pulp-dentin systems frequently results in fibrotic repair rather than true regeneration, an outcome decisively shaped by the surrounding inflammatory microenvironment. This review synthesizes how immunomodulatory biomaterials have evolved from passive structural scaffolds into active regulators of the healing niche that direct immune cell recruitment, macrophage polarization, cytokine signaling, and the spatiotemporal resolution of inflammation. The cellular and inflammatory challenges specific to mineralized and soft craniofacial tissues, the periodontium, and the confined dentin-pulp complex are considered in turn, alongside the principal fabrication strategies and delivery platforms through which immunological instructions are encoded into materials: electrospinning, surface modification, core-shell architectures, nanoparticles, hydrogels, three-dimensional printing and bioprinting, calcium silicate cements, and exosome-based delivery. Particular attention is given to tuning composition, architecture, degradation, and release kinetics so that host responses shift from a pro-inflammatory toward a pro-regenerative state and infection control is coupled with regenerative success. Clinical translation nevertheless remains constrained by patient-specific immune variability, the difficulty of reproducing complex oral microenvironments, and limited long-term in vivo evidence in contaminated defect models. The next generation of these materials will likely function as multiscale, stimuli-responsive platforms that sense local inflammatory conditions and adapt to them, actively orchestrating immune responses and tissue regeneration rather than merely supporting repair.