A neurovascularized bone regeneration strategy for mandibular and alveolar bone defects based on elastin-like biomaterials

Abstract The regeneration of craniofacial bone defects requires biomaterials that provide more than mechanical support, enabling coordinated osteogenesis, angiogenesis, and innervation. To address this challenge, we designed a composite scaffold based on elastin-like polypeptides (ELPs) functionalized with bioactive peptides to recruit endothelial and sensory neuron cells, allow degradation, and ensure hydroxyapatite distribution for enhanced mineralization. The scaffold was evaluated in two critical-size defect models, the rat mandible and minipig alveolar bone, promoting progressive bone formation, robust vascularization, neural infiltration, and controlled immune response. In rats, the ELP scaffold achieved 36% bone fill at 4 weeks, compared with 24% for the control material Collapat® and 16% in untreated defects, accompanied by dense vascular and neural networks. Immune cell infiltration was also significantly reduced relative to Collapat®, indicating improved immunotolerance. In minipigs, ELP-treated defects showed 36% new bone formation after 8 weeks, characterized by well-organized lamellar bone, integrated osteocytes, and mature neurovascular networks. Compared with commercial matrices, the ELP scaffold consistently demonstrated superior outcomes in bone formation, tissue integration, and functional innervation. Overall, this biomaterial promotes synchronized neurovascularized bone regeneration while maintaining excellent biocompatibility, remodeling capacity, and regenerative efficacy, making it a promising candidate for mandibular and alveolar bone repair.