Stem cell-based tissue engineering for the regeneration of periodontal structures: A systemic review of current progress and barriers

Periodontal disease (PD) is characterized by gum inflammation, ranging from reversible gingivitis to irreversible periodontitis. Periodontitis compromises the foundation of oral health by degrading periodontal tissues that support teeth, namely the periodontal ligament (PDL), underlying alveolar bone (AB), cementum (CM), and the gingiva. Disruption of the structural integrity of teeth leads to a multitude of oral issues and eventual tooth loss. The focus of this review is to explore treatment modalities that use stem cell therapies and tissue engineering to aid in tissue regeneration while also overcoming the intracellular molecular pathways that lead to tissue degradation. Research from PubMed and Google Scholars, from 2000 to 2025 was conducted, applying predefined inclusion and exclusion criteria. The combined findings show that orally-derived and non-oral stem cells have promising regenerative potential, specifically: periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), stem cells from the apical papilla (SCAPs), bone marrow-derived stem cells (BMSCs), adipose tissue stem cells (ADSCs), and human umbilical cord mesenchymal stem cells (UCMSCs). Among the different stem cell types reviewed, PDLSCs revealed the highest regenerative potential of periodontal tissue in vivo, particularly when combined with bioengineered scaffolds. However, challenges such as limited clinical translation, minimal autologous availability, and adverse immune responses remain significant barriers. Furthermore, optimizing scaffold design and refining immunomodulatory strategies are the next steps in making stem cell-based tissue engineering clinically viable for periodontal regeneration.