Developing Salivary Components to Restore Oral Health

On this page

  1. Goal
  2. Background
  3. Gaps and Opportunities
  4. Impact
  5. Current Portfolio
  6. References

September 2022

Integrative Biology and Infectious Disease Branch
Division of Extramural Research

Back to top

Goal

The goal of this initiative is to encourage interdisciplinary research that harnesses the functional components of saliva towards therapeutics. This initiative will encourage studies to develop the salivary components to restore health and resilience of the oral cavity. It is expected that outcomes from this research will facilitate development of highly effective surrogate saliva for clinical applications. This initiative is not focused on development of salivary biomarkers or diagnostics.

Back to top

Background

Saliva plays an essential role in maintaining oral health1. Each salivary component has essential roles, loss of which compromises oral health. As such, replenishing these components is essential for processes such as enhancing wound healing, increasing biomaterial survival, and replenishing enamel mineralization. When salivary flow is reduced, oral health issues such as dental caries, fissuring of the oral mucosa, oral fungal infections, taste changes, halitosis, or burning mouth can develop. Reduction in salivary flow and composition may occur due to radiation-induced xerostomia in patients undergoing treatment for head and neck cancers, autoimmune disease (Sjögren's Disease), medications and aging. Despite the need for effective saliva substitutes, the efficacy of saliva substitutes and stimulants remains limited2. Existing saliva substitutes differ significantly from human saliva in pH, osmolarity and/or electrical conductivity and offer inadequate and short-term relief3.

Human saliva consists of approximately 99.5% water; the remaining 0.5% is responsible for the various functions attributed to saliva. This 0.5% consists of glycans, proteins, lipids, ions and other biomolecules. Saliva has a significant role in remineralization of dental enamel. It not only has a buffering capacity to neutralize the oral cavity's low pH generated under acidic conditions, but also acts as a carrier of essential ions, such as fluoride, calcium and phosphate, which facilitates enamel remineralization4. The role of salivary defenses and their effect on the oral microbiome is increasingly being recognized as a complex relationship; saliva provides a pellicle which is subsequently colonized during the first stage of biofilm formation, it provides nutrients to the microbiota which in turn buffer saliva and maintain it at a healthy pH. In addition, the effect of saliva as a microenvironmental factor during the different phases of wound healing is well-recognized5. Cells in the buccal mucosa turnover two times faster than those in skin epithelium. Saliva continuously lubricates the wound, reducing tissue dehydration and cell death, and provides various cytokines, chemokines, and growth factors to promote wound healing. In case of dental implants, oral biosensors, bone substitutes and membranes used widely in dentistry possess different properties focused on improving the healing process when in contact with oral tissues. The early saliva interaction with biomaterials manufactured for oral rehabilitation is known to impair some positive features present in biomaterials related to quick cellular adhesion and proliferation, such as surface hydrophilicity, cellular viability and antibacterial properties6. The use of sugar-free gum, which is positively linked to reduced dental caries, depends on mastication to stimulate saliva secretion. The increased incidence of dental caries in patients with salivary hypofunction is directly linked to reduced salivary clearance rates.

Back to top

Gaps and Opportunities

Recent developments in salivary gland transcriptomics and its integrations with saliva and blood plasma components have enabled linking human salivary proteins to their source, identification of salivary-gland-specific genes, uncovering gene repertoires linking examinations of salivary components in context-specific manner7, 8. These advances provide new opportunities that include developing:

  • Saliva-based therapeutics to enhance enamel remineralization, wound healing, increased biomaterial survival and maintenance of healthy oral microbiota in the oral cavity.
  • Effective saliva surrogates for replenishment of drug-induced or post-radiation xerostomia.
Back to top

Impact

This initiative will address unmet clinical therapeutic needs in areas of dry mouth, dental materials, remineralization, oral immunology and cellular therapies that recapitulate properties of human saliva containing antimicrobial components and incorporating its immunomodulatory and remineralization properties. This concept is expected to lead to the development of novel therapies to modulate imbalances in the compositions of saliva at the individual’s level resulting from injury, illness, individual deficiencies and to enhance growth and repair of oral tissues to promote and restore oral health. It is well recognized that the context of use of saliva highly determines the components in the saliva that need to be replenished. This initiative aligns with that recognition and the need for better understanding of these contexts and components, thus laying the groundwork for new therapies and technologies.

Back to top

Current Portfolio

NIDCR currently funds the Human Salivary Proteome Wiki9 that represents a community-based open platform that is accessible to the biomedical community to explore salivary proteins of relevance to human health and disease. NIDCR funds research on salivary proteins, nucleic acids and glycans with antimicrobial properties and those affected in autoimmune Sjögren’s disease and xerostomia. In addition, NIDCR funds numerous studies on salivary gland regeneration and saliva based clinical research. However, there is a lack of projects focused on application of salivary components toward restoring health of the oral cavity.

Back to top

References

  1. Uchida H, Ovitt CE. Novel impacts of saliva with regard to oral health. J Prosthet Dent. 2022 Mar;127(3):383-391.
  2. Riley P, Glenny AM, Hua F, Worthington HV.Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database Syst Rev. 2017 Jul 31;7(7):CD012744.
  3. Spirk C, Hartl S, Pritz E, Gugatschka M, Kolb-Lenz D, Leitinger G, Roblegg E.Comprehensive investigation of saliva replacement liquids for the treatment of xerostomia. Int J Pharm. 2019 Nov 25;571:118759.
  4. Farooq I, Bugshan A. The role of salivary contents and modern technologies in the remineralization of dental enamel: a narrative review. F1000Res. 2020 Mar 9;9:171.
  5. Waasdorp M, Krom BP, Bikker FJ, van Zuijlen PPM, Niessen FB, Gibbs S. The Bigger Picture: Why Oral Mucosa Heals Better Than Skin. Biomolecules. 2021 Aug 6;11(8):1165.
  6. Kunrath MF, Dahlin C. The Impact of Early Saliva Interaction on Dental Implants and Biomaterials for Oral Regeneration: An Overview. Int J Mol Sci. 2022 Feb 11;23(4):2024.
  7. Saitou M, Gaylord EA, Xu E, May AJ, Neznanova L, Nathan S, Grawe A, Chang J, Ryan W, Ruhl S, Knox SM, Gokcumen O.Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva. Cell Rep. 2020 Nov 17;33(7):108402.
  8. Huang N, Pérez P, Kato T, Mikami Y, Okuda K, Gilmore RC, Conde CD, Gasmi B, Stein S, Beach M, et al. SARS-CoV-2 infection of the oral cavity and saliva. Nat Med. 2021 May;27(5):892-903.
  9. Lau WW, Hardt M, Zhang YH, Freire M, Ruhl S. The Human Salivary Proteome Wiki: A Community-Driven Research Platform. J Dent Res. 2021 Dec;100(13):1510-1519. doi: 10.1177/00220345211014432.
Back to top
Last Reviewed
April 2024