Beyond Bone Replacement: The Role of Osteogenesis, Angiogenesis, and Osteoimmunology in Bioactive Scaffold-Based Craniofacial Reconstruction

Abstract

Bioactive scaffolds represent a promising frontier in craniofacial reconstruction by combining osteoinductive and osteoconductive properties to enhance bone tissue engineering outcomes. Despite advances in scaffold design, biological integration, and manufacturing techniques such as 3D bioprinting, several biological, biomechanical, manufacturing, and translational challenges limit their clinical application. This narrative review synthesizes evidence from 28 studies (2012–2025), highlighting key issues including BMP-2 dosing controversies, strength-porosity paradox, scaffold degradation kinetics, and regulatory barriers. Quantitative data reveal compressive strengths ranging from 2.3 to 120 MPa depending on material, porosity levels of 60–80%, and variable vascularization metrics (up to 45 vessels/mm²). Critical gaps include inconsistent animal-to-human model translatability and lack of validated pore size standards. Emerging strategies such as patient-specific implants, stem cell incorporation, and bioresorbable materials show promise but require rigorous testing. This review underscores the need for mechanistic understanding of scaffold-host interactions and calls for standardized clinical trials to bridge translational gaps. Future research should address scaffold degradation predictability and regulatory compliance to facilitate clinical translation.