Biomaterials to biofabrication: advanced scaffold technologies for regenerative endodontics

Abstract Scaffold systems are fundamental to regenerative endodontics, functioning as structural frameworks and delivery vehicles for bioactive cues essential to tissue regeneration. This review comprehensively examines scaffold types, functions, and translational challenges in endodontic regeneration. Scaffolds are classified into natural, synthetic, and hybrid matrices with unique mechanical and biological profiles. Advances in nanotechnology, 3D and 4D bioprinting, and smart biomaterials have significantly improved scaffold functionality. Smart scaffolds enable the controlled release of growth factors, antimicrobial agents, and gene-functionalized molecules, facilitating angiogenesis, stem cell differentiation, and infection control. Hybrid scaffolds, such as those combining collagen and gelatin methacryloyl (GelMA), provide customized degradation, biocompatibility, and mechanical strength. Innovative systems such as magnetic nanoparticle-triggered release and responsive hydrogels address vascularization and immune modulation limitations. Clinically, platelet-rich fibrin (PRF), concentrated growth factor (CGF), and decellularized extracellular matrix (dECM) have shown success in promoting root development, pulp vitality, and periapical healing. Despite these advances, obstacles remain, including regulatory hurdles, standardization of protocols, and long-term clinical validation. Integrating AI-driven scaffold design, digital twin simulations, and organ-on-chip models holds promise for personalized therapies. Establishing scaffold-based regeneration as a standard clinical approach will require harmonized practices, scalable biomaterial production, and robust clinical outcome assessments.