Salivary Liquid Biopsy: Toward More Tolerable and Patient-Friendly Dental Care

Liquid biopsies are methodologies which enable the detection and monitoring of the expression of molecules associated with diseases. Blood represents the biological matrix most frequently biopsied; however, its collection is often unpleasant for patients. Consequently, the analysis of other biofluids such as saliva and gingival crevicular fluid (GCF) is emerging as a minimally invasive methodology to identify markers related to both systemic and oral diseases. Oral diseases represent a significant global health burden, affecting individuals across all stages of life. These conditions often lead to symptoms that impair the overall quality of life and, in some cases, increase the risk of systemic disorders occurrence. While many oral diseases are potentially avoidable, current prevention strategies remain insufficient—even in high-income countries. Among the more prevalent dental disorders, Periodontitis (PD) and Recurrent Aphthous Stomatitis (RAS) emerge as two significant challenges, as they both lack effective prevention strategies. Moreover, conventional treatments for those conditions are often inadequate in mitigating symptom onset and the associated distress experienced by patients, thereby underscoring the need for innovative strategies. In this regard, a promising approach is the engineering of bioactive molecules within biodegradable gels, aimed at enhancing site-specific drug delivery while minimizing systemic exposure and related adverse effects. This strategy has been recently applied in the management of periodontal disease, where doxycycline—an agent with both antimicrobial activity and adjunctive properties, including modulation of the host inflammatory response, inhibition of matrix metalloproteinases, and promotion of tissue repair—has been incorporated into a biodegradable polylactic–polyglycolic acid gel (DOX). While this formulation shows potential in promoting periodontal tissue health, clinical validation of DOX is still necessary. Another factor frequently contributing to delayed dental treatment is the fear many patients experience toward dental appointments. As a result, care is often postponed until symptoms become intolerable. This postponement can significantly compromise patients’ clinical outcomes, particularly in children, for whom early dental care is crucial to intercept developing conditions, minimize complications, and preserve long-term oral health. In this context, an emerging strategy to reduce distress in pediatric patients involves facilitating interactions with trained animals prior to entering the healthcare setting. Although rigorous scientific validation of this approach within clinical dentistry is still limited, multiple observations suggest that contact with animals can significantly reduce distress in children—including those diagnosed with neurodevelopmental disorders. In this context, the present study aims to employ established proteomic and immunologic assays to identify potential biomarkers of PD and RAS through the analysis of oral biofluids. Although these conditions differ clinically, they share key pathogenic pathways, particularly regarding inflammation and the influence of the oral microbiota. GCF will be employed to evaluate molecularly the therapeutic efficiency of DOX with the aim of providing solid outputs that could support its application in the therapy of PD. Finally, the liquid-biopsy approach will be used as a minimally invasive method to measure widely recognized stress markers, thereby providing a scientific basis for validating the stress-relief effects of pet therapy throughout dental appointments