Dental follicle stem cells (DFSCs) originate from the dental follicle during tooth development and possess multilineage differentiation potential, contributing to periodontal tissue regeneration, bone repair, and immunomodulation. This review highlights the recent advances in the application of DFSCs and biological scaffolds for regenerative medicine, with a focus on oral and craniofacial tissue. DFSCs exhibit key advantages for regenerative therapies, including high accessibility, robust self-renewal capacity, and multipotent differentiation potential, enabling their differentiation into odontogenic (dentin- and enamel-forming), osteogenic, and fibroblastic lineages. We discuss the embryonic origin of DFSCS and their unique ability to maintain stable cellular properties in long-term in vitro culture. Importantly, DFSCs play a pivotal role in tooth morphogenesis, periodontal tissue formation, and craniofacial bone regeneration, making them promising for functional oral tissue restoration. A critical aspect of DFSC-based regeneration is the integration with bioactive scaffolds, which provide structural support, promote cell adhesion, proliferation, and differentiation, and facilitate vascularization. We analyze how scaffold properties, such as biodegradability, porosity, and permeability, influence DFSC behavior and therapeutic outcomes. Finally, we explore future challenges and opportunities in optimizing DFSC-scaffold interaction, emphasizing advancements in biomaterial design and emerging bioengineering technologies. Preliminary evidence suggests that integrating DFSCs with engineered scaffold systems may offer potential benefits for personalized regenerative therapies, though further validation is required before clinical translation. Such approaches could contribute to advancing tooth and craniofacial reconstruction strategies. This review consolidates existing insights and explores potential avenues for future research to support advancements in DFSC-based regenerative medicine.
Impact Statement
Dental follicle stem cells combined with bioactive scaffolds offer transformative potential in oral/craniofacial regeneration. Their multipotency enables regeneration of tooth structures, periodontal tissues, and bone. This synergy helps mitigate current challenges in reconstruction and offers promising functional repair solutions. This approach contributes to the progression of personalized regenerative therapies, with potential implications for dentistry and maxillofacial surgery. Future refinements in scaffolds and stem cell technology could revolutionize the treatment of tooth loss, periodontitis, and defects, enhancing outcomes while reducing dependence on synthetic implants.
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