Hydrolysis-resistant resin networks for durable and multifunctional dental restorations - Summary: The short average service life and the rising incidence of secondary caries currently hamper the reliability of existing dental composite restorations. This underlines the pressing need for innovative, long-lasting dental restorations composed of novel resin networks, multifunctional fillers and additives, and adhesive constituents. Our goal is to create superior resins and resin composites for dental restorations. These new restorations will surpass the capabilities of the extant methacrylate, ester-based analogs. Our strategy centers on formulating and testing novel resins and resin composites that resist hydrolysis and enzymolysis and possess antimicrobial, protein-repellent, and therapeutic attributes, consequently producing dental adhesives and resin composites with performance and a lifespan exceeding their methacrylate-based equivalents currently being used in dental clinics. We will achieve our goal in three Specific Aims. Aim 1: We will develop and evaluate biostable hybrid resin networks that may withhold the harsh challenges in patients’ oral environments. By strategically alternating the packing of the methacrylate units with hydrophobic styrene-derivative units, we will protect ester-groups from hydrolysis, enzymolysis, and cariogenic bacteria attack. The novel biostable hybrid resin networks will encompass an acidic component for self-etch dental adhesives and multifunctional components for various needs in dental restorations. We'll then employ a highly sensitive method to quantitively assess and rank these hybrid resins against traditional ester-based resins. Aim 2: We plan to formulate and develop new multifunctional hybrid resins and resin composites. These materials should match or be better than their ester-based counterparts regarding antimicrobial, protein-repellent, and therapeutic aspects. We hypothesize that these hybrid resin networks can seamlessly integrate with the functional additives and fillers previously devised for conventional ester-based dental resin networks. Aim 3: We will subject the newly developed resins and composites to rigorous testing as restorations (combinations of dental adhesives and resin composites) on extracted human teeth under static and cyclic loadings. We will confirm their long-term performance in the most clinically relevant scenarios by simulating real-world challenges such as clinical aging, thermal cycling, and cariogenic biofilm exposure. Successful completion of the proposed Aims will result in the production of multifunctional, durable dental resin restorations adept at addressing various needs for treating dental cavities.