Revolutionizing Tooth Regeneration: Innovations from Stem Cells to Tissue Engineering

Purpose: Tooth regeneration research aims to bridge historical milestones with cutting-edge molecular insights and biomaterial strategies to revolutionize regenerative dentistry. It focuses on decoding the genetic underpinnings and molecular signaling pathways that govern tooth morphogenesis. This understanding is crucial for advancing the development of innovative and effective dental restoration techniques that can potentially replace conventional methods. Methods: This comprehensive review integrates historical perspectives with contemporary scientific inquiries, emphasizing the role of advanced techniques such as single-cell sequencing, induced pluripotent stem cells (iPSCs), and organoid culture in unraveling the complexities of tooth development. Additionally, this review explores the use of proteomics, phosphoproteomics, and genetic engineering systems in studying molecular signaling pathways involved in tooth development and morphogenesis. Results: This review highlights the pivotal role of induced pluripotent stem cells (iPSCs) in tooth regeneration, shedding light on their transformative applications. Furthermore, the integration of advanced computational analysis with single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) has unveiled previously unknown populations of epithelial support tissues, offering profound insights into dental tissue differentiation. Additionally, this review discusses the advances in biomaterials and bioengineering approaches, emphasizing the intricacies of neurovascular integration, which is crucial for successful tooth regeneration. Conclusion: This comprehensive review provides a holistic understanding of tooth regeneration, emphasizing the historical milestones, molecular insights, and biomaterial strategies that have shaped the field. The integration of advanced techniques and innovative approaches holds promise for transformative applications in regenerative dentistry, paving the way for future advancements in tooth regeneration.