Project Summary/Abstract: Candida-associated denture stomatitis (CADS), due to Candida colonization and
biofilm formation on the denture surface, is a significant clinical concern and affects up to 67% of denture
wearers. Fungal biofilms serve as a reservoir for various oral bacteria that cause oral health problems and
systemic infections. Currently, strategies for controlling CADS are clinically challenging and have high reinfection
rates, particularly in elderly and/or immunologically- or medically-compromised patients.
This proposal is being submitted in response to NIDCR RFA-DE-24-004 and aims to use natural salivary
anticandidal peptides/proteins in multilayer coatings on dentures to control CADS. We have previously
demonstrated that covalently binding functional polymers, such as poly(methacrylic acid) (PMAA), onto
conventional dentures enhances the binding of cationic anticandidal biomolecules, including histatin 5 (H-5), a
major salivary polypeptide of the histatin family with high anticandidal activity. The PMAA functionalized denture
material maintained the physical/mechanical properties of the original resin. We have further used a layer-by-
layer (LBL) self-assembly technology (alternating the deposition of oppositely charged polyelectrolytes) by
pairing H-5 with hyaluronic acid (HA), an anionic unsulfated salivary glycosaminoglycan, to form H-5/HA
multilayer coatings, resulting in an increase in the H-5 content on the surface of the denture material. Using H-5
as the outermost layer, the LBL self-assembled H-5/HA multilayer coatings inhibited Candida adhesion and had
long-lasting (weeks to months) anticandidal effects that blocked Candida biofilm formation. The LBL coatings
were stable and remained on the denture surface after extensive mechanical brushing (e.g., >20,000 cycles of
brushing).
The long-term goal of this project is to use normal salivary components as natural and safe antifungal
therapeutics for controlling Candida biofilm formation and managing CADS. The main objectives of this proposal
are to evaluate the efficacy of salivary anticandidal peptides/proteins in multilayer coatings for controlling
Candida biofilm formation on rat dentures and in a novel rat denture stomatitis model. The specific aims of the
proposed research are: (1) to fabricate rat dentures with salivary anticandidal peptide/protein-based LBL
multilayer coatings; (2) to evaluate the anticandidal activity and biocompatibility of the functionalized and coated
dentures in vitro; and (3) to evaluate the preclinical efficacy of the dentures coated with salivary anticandidal
peptide/protein multilayers in vitro and in vivo. If successful, this new denture technology will be the first
therapeutic denture using natural salivary components to provide a long-term biofilm-controlling effects, prevent
unnecessary drug exposure, and minimize the risk of developing Candida resistance. These anticandidal
technologies will not only have a significant impact on clinical dentistry but may also provide new materials for a
variety of medical devices (e.g., catheters, endotracheal tubes) and reduce hospital-acquired infections.
