Organoid-based modeling and regenerative strategies for salivary gland dysfunction

Xerostomia, a pathological condition resulting from hyposalivation due to salivary gland (SG) dysfunction, severely affects a patient's health, quality of life, and healthcare costs. Despite its high prevalence, long-term curative treatments remain unavailable, leaving patients with lifelong symptom management. Permanent SG damage caused by disease or injury exacerbates this condition, highlighting the urgent need for regenerative solutions. Salivary gland organoids (SGOs) have emerged as promising in vitro models for studying SG homeostasis and pathology. SGOs serve as physiologically relevant three-dimensional models, enabling the study of tissue renewal, stem cell-niche interactions, and responses to genetic mutations, drugs, or injury. Additionally, advances in regenerative medicine, including stem cell-or organoid-based therapies integrated with bioengineering approaches, have the potential to develop future treatments. In this review, we summarize the latest progress in SGO development, explore its potential for modeling diseases and injuries, and discuss emerging regenerative strategies for restoring SG function. By deepening our understanding of SG physiology and diseases, these studies pave the way for therapeutic or regenerative approaches that have the potential to provide lasting relief for patients with xerostomia.