State-of-the-art molecular compounds in artificial salivary substitutes tackling xerostomia and oral mucositis

The oral mucosa relies on constant salivary lubrication as well as on epithelial and immune barriers to maintain its homeostasis and normal function. Disruption of these can be triggered by salivary gland (SG) damage following radiotherapy and/or chemotherapy for head and neck cancer (HNC) patients. This SG injury leads to major complications, particularly dry mouth (also known as xerostomia, XM) and oral mucositis (OM). Xerostomia with hyposalivation is associated with oral complications such as dental caries, dysphagia, candidiasis, and taste disturbances. In contrast, OM develops as a result of epithelial injury and inflammatory cascades, leading to pain, burning, altered dietary intake, and poor nutrition. Together, XM and OM severely compromise the quality of life of HNC patients worldwide. Currently, effective curative treatments remain limited due to the lack of functional SG tissue after HNC therapy, highlighting the urgent need for innovative strategies. Artificial salivary substitutes, ranging from biological to synthetic, provide a safe and effective means of enhancing oral hydration and lubrication. These formulations encompass traditional components like mucins and growth factors, as well as emerging agents based on lipids, carbohydrates, and plant-derived compounds. In this narrative review, we provide current insights into the protective biochemistry barriers of the oral mucosa elicited by XM and OM, and discuss emerging salivary mimetic compounds aimed at restoring mucosal homeostasis and immunoepithelial barrier functions.