DENTAL PULP STEM CELLS AND MAXILLOMANDIBULAR REGENERATION: CURRENT EVIDENCE, MECHANISMS, AND FUTURE PERSPECTIVES - A NARRATIVE REVIEW

Abstract

Reconstruction of maxillomandibular defects arising from trauma, tumour resection, congenital anomalies, and periodontal disease remains a major challenge in oral and maxillofacial surgery, as conventional autografts, allografts, and xenografts are limited by donor site morbidity, restricted graft supply, and unpredictable integration. Dental pulp stem cells (DPSCs), a population of neural crest-derived mesenchymal stem cells isolated from the dental pulp of extracted teeth, have emerged as a promising cell source for craniofacial tissue regeneration owing to their high proliferative capacity, multilineage differentiation potential, low immunogenicity, and accessibility from routinely discarded teeth. This narrative review summarises the biology, classification, isolation, and characterisation of DPSCs; the cellular and molecular mechanisms by which they contribute to osteogenesis, neurogenesis, immunomodulation, and angiogenesis; and the tissue engineering strategies, including natural and synthetic scaffolds, growth factor delivery, and three-dimensional bioprinting, used to translate their regenerative potential into clinically applicable constructs. Clinical applications in alveolar bone regeneration, mandibular reconstruction, maxillary sinus augmentation, periodontal regeneration, and nerve repair are discussed alongside a comparison of DPSCs with other dental- and non-dental-derived stem cell sources. Despite encouraging preclinical and early clinical evidence, translation of DPSC-based therapies is limited by poor post-transplantation cell survival, lack of standardised isolation and culture protocols, scarcity of long-term controlled clinical trials, and regulatory and infrastructural barriers. Emerging strategies such as DPSC-derived extracellular vesicles, genetic and epigenetic modification, smart biomaterials, and artificial intelligence-guided scaffold design offer promising avenues to overcome these limitations. Continued interdisciplinary research will be essential to establish DPSC-based therapeutics as a predictable, evidence-based option for maxillomandibular regeneration.