Cellular and Molecular Mechanisms of Salivary Gland Development and Regeneration: Implications for Tissue Engineering and Regenerative Medicine

Salivary glands are essential for oral health, but their function can be compromised by cancer, autoimmune disorders, infections, and physical traumas, severely impacting quality of life. There is currently no cure for salivary gland dysfunction, and treatment is symptomatic. Objective: To explore the cellular and molecular mechanisms involved in the development, maturation, and regeneration of salivary glands, with a focus on tissue engineering and regenerative medicine. Methods: A comprehensive review was conducted using PRISMA and information was fetched through PUBMED, EMBASE, Medline, and Google Scholar databases. Results: The FGF pathway, part of the growth factor family, plays a significant role in salivary gland homeostasis, while the Wnt pathway is crucial for gland maturation. Various receptors and signaling molecules are involved in the gland's functioning. Recent advancements in regenerative medicine have demonstrated that activating endogenous stem cells can lead to positive outcomes in restoring injured salivary glands. Technological advancements in 3D tissue culturing using patient cells have enabled the creation of functional artificial salivary gland organs. However, no cell line completely mimics natural salivary gland cells, and their inherent tumorigenic potential delays their therapeutic application. Conclusions: Understanding these mechanisms is vital for developing effective therapies. While recent advancements show promise, further research is necessary to create safe, accurate cell lines for therapeutic use. This knowledge is crucial for establishing therapeutic avenues that could potentially lead to direct regeneration, reconstruction, and replacement of functioning salivary glands.