From Bench to Bone: Translational Pathways of Nanomaterial-Based Therapies in Craniomaxillomandibulofacial and Cranial Vault Reconstruction.

Craniomaxillofacial and cranial vault reconstruction remain limited by donor-site morbidity, infection, inadequate vascularization, incomplete osseointegration, and poor adaptation of conventional grafts to complex patient-specific anatomy. Nanomaterial-based therapies offer a translationally attractive strategy. Nanoscale hydroxyapatite, calcium phosphates, mesoporous silica, metallic nanoparticles, bioactive glasses, polymeric carriers, injectable nanocomposite hydrogels, extracellular vesicle-inspired systems, and nanostructured coatings can act on several targets at once, including osteogenesis, angiogenesis, immune response, antimicrobial activity, mechanical reinforcement, and controlled release. This review synthesizes recent evidence on nanomaterial-enabled bone regeneration for craniomaxillofacial and cranial vault reconstruction, placing emphasis on the pathway from in vitro mechanisms to animal models, additive manufacturing, patient-specific implants, and early clinical translation. 3D-printed calcium phosphate or hydroxyapatite-based patient-specific scaffolds are currently supported by the strongest near-clinical evidence, whilst immunomodulatory, bioprinted, injectable, and drug-delivering nanocomposites remain largely preclinical. Growth-factor-independent strategies based on ionic signaling, dipyridamole-enhanced adenosine signaling, nanosilicate-mediated osteogenesis, Wnt/beta-catenin mechanotransduction, and nanoparticle-mediated osteoimmunomodulation may reduce reliance on recombinant bone morphogenetic proteins. However, large-animal validation, long-term biodistribution, nanotoxicology, sterilization, manufacturing reproducibility, and regulatory classification remain major barriers. Future clinical translation will require rational scaffold design, anatomical indication-specific testing, antimicrobial integration, and harmonized regulatory evidence packages.