Dentin–Pulp Regeneration: A Requirement-Driven Comparison of Scaffold-Based, Scaffold-Free, and Hybrid Strategies

The failure of the dentin-pulp complex in many situations can lead to problems in tissue function, and therefore there is a need for regenerative strategies that can restore the structural and biological integrity of the tissue. In this review, the different approaches to dentin-pulp regeneration, including single-material natural scaffolds, single-material synthetic scaffolds, scaffold-free strategies, and hybrid/composite scaffolds, are evaluated. These approaches are then compared based on seven criteria for successful regeneration: biocompatibility, cellular activity, structural stability, controlled degradation, vascularization, tissue organization, and reproducibility/feasibility in a clinical setting. At present, the evidence points to the fact that no individual strategy is consistently better. Natural scaffolds, for example, support biological interactions but have variable characteristics and insufficient mechanical properties. Synthetic scaffolds offer greater control, predictability, and reproducibility, but lack some of the inherent bioactivity of natural scaffolds. Scaffold-free strategies maintain cell-to-cell interactions and ECM formation but are less stable and reproducible. These hybrid/composite scaffolds provide a potentially beneficial scaffold structure in which they can combine biological and physical characteristics. The added complexity of a hybrid/composite approach, however, adds even more challenges. Overall, the successful dentin-pulp regeneration may be more dependent on defining the optimal strategy to satisfy the needs of the dentin-pulp complex than on identifying the best and optimal material.