From Structural Complementarity to Functional Synergy: Advantages and Challenges of Combining Demineralized Dentin Matrix and Hydrogels for Bone Defect Repair

Demineralized dentin matrix (DDM) provides intrinsic bioactivity and osteoinductive cues for bone regeneration but is limited by its rigidity and material heterogeneity. Advances in hydrogel engineering-encompassing biomimetic polymers and tunable network architectures-offer effective strategies to complement and enhance the regenerative performance of DDM. This review analyzes DDM biology, hydrogel design, and their synergistic integration into composite scaffolds. DDM-hydrogel composites leverage endogenous osteoinductivity with injectability, controlled degradation, and microenvironmental regulation, orchestrating osteogenesis, angiogenesis, and osteoimmune balance. Despite encouraging preclinical outcomes, several challenges remain, including donor- and batch-dependent variability of DDM, mismatched degradation kinetics, suboptimal mechanical-biological integration, and the absence of standardized manufacturing and safety frameworks. Emerging strategies-such as multiscale nanoreinforcement, stimuli-responsive or degradation-programmable hydrogel networks, microfluidic-assisted fabrication, and bioactivity grading systems-offer rational pathways to address these limitations. Promising translational opportunities exist for personalized maxillofacial reconstruction, periodontal regeneration, and advanced bone graft substitutes. This review offers mechanistic understanding and guidance for developing functionally integrated and clinically viable DDM-hydrogel bone regeneration systems.