Nanomaterials and 3D-Printed Scaffolds in Pulp Regeneration: A Perspective on Hierarchical Design Principles and Translational Barriers

Loss of pulp vitality, particularly in immature permanent teeth, is still managed predominantly by substitutive procedures that replace the dentin-pulp complex with inert materials. Regenerative endodontic procedures (REPs) aim to restore a vital, functional tissue, but their outcomes are unpredictable because the blood-clot scaffold offers little control over cell density, signaling, or architecture, and the tissue formed is frequently reparative rather than truly pulp-like. Two technologies are often proposed to address this gap: nanomaterials, which provide bioactivity, antimicrobial function, mechanical reinforcement, and controlled delivery at the scale of the extracellular matrix; and additive manufacturing, which provides control over macro-scale geometry and porosity. In this Perspective, we synthesize established concepts from dental pulp tissue engineering, biomaterials science, and endodontics, and we propose a four-layer conceptual framework (macro-architecture, vascular-permissive porosity, nanoscale cues, and temporally programmed biochemistry) that can guide the design of printed, nanostructured scaffolds for the root canal. We then discuss the principal barriers to translation: the narrow safety window of antimicrobial nanomaterials, mechanical and degradation matching, vascularization and innervation in a confined canal, non-standardized preclinical models, and regulatory complexity. We argue that acellular, cell-homing constructs are the most realistic first clinical step, and we outline research priorities. The framework is hypothesis-generating and has not been experimentally validated.