In its recent RFA-DE-16-007, the NIDCR emphasizes a need for new studies on Class V restoratives with the ultimate goal to develop new approaches/materials that would outperform glass ionomer cements (GICs) and/or resin- modified GICs, currently most frequently used for these restorations. The RFA calls for interdisciplinary research that would address the specific concerns stemming from generally deteriorated health of elderly population with reduced salivary flow and compromised periodontium. Our group has been on the fore-front of the research on polymeric, bioactive remineralizing dental materials based on amorphous calcium phosphate (ACP) for two decades. We have already successfully designed ACP polymeric materials capable of efficiently restoring lost tooth mineral via sustained release of calcium (Ca) and phosphate (PO4) ions. These materials were intended for base/lining, orthodontic and endodontic applications. In this submission, we propose to develop new, antimicrobial (AM) and remineralizing ACP composites which will physico-chemically, mechanically and biologically outperform the conventional Class V restoratives. We will build upon our understanding of ACP chemistry and solution thermodynamics as well as remineralizing ACP polymeric systems. We will add the AM functionality to ACP composites to make them a polyvalent tool for combating root caries. For that purpose, we will synthesize new AM monomers and fine-tune the resins to improve the polymerization shrinkage and control polymerization stress while attaining high degrees of vinyl conversion, minimize leachability of the unreacted monomers and/or degradation products and enhance bonding to dentin. The overall working hypothesis is that a concomitant, long-term AM and remineralizing function is attainable without impeding the critical physicochemical, mechanical and biological properties of composites. This hypothesis will be tested through the following Specific Aims (SAs): SA1 - Synthesis and validation of new AM monomers; SA2 - Synthesis and characterization of ACP filler; SA3 - Formulation, biocompatibility, physicochemical and mechanical evaluation of copolymers and composites; SA4 - AM activity of resins and composites, and SA5 - Remineralizing efficacy of composites. The proposed research will yield a prototype AM ACP composite for Class V restorations recommendable for testing in an animal study and/or clinical trial.
With root caries prevalence in older adults being reportedly as high as 90 %, the expected demographic elderly boom will inevitably lead to a substantial increase in need for root caries treatments. Conventional Class V restoratives do not address comprehensively the specific challenges typical for elderly population with generally deteriorated health, reduced salivary flow and compromised periodontium. Glass ionomer cements (GICs) and resin-modified GICs, predominantly used for this purpose, exhibit a burst release of fluoride (F) and no sustained remineralization. Generally, the antimicrobial (AM) activity of these restoratives has been neglected, and clinically marginalized. This proposal, submitted in response to the RFA-DE-16-007, leans strongly on our group?s unique experience with amorphous calcium phosphate (ACP)-based dental materials. By applying lessons learned from the structure/composition/property studies of polymeric ACP systems, we propose to design AM remineralizing polymeric composites capable of simultaneously responding to microbial challenges due to the presence of AM functionalities in their polymer phase, and regenerating tooth mineral phases due to the bioactivity of ACP filler. Both AM and remineralizing function will be long-lived. New, resin-compatible, AM poly-functional monomers and coupling agents and ACP will be incorporated into highly cross- linked, yet flexible resins. The AM resins and the ensuing ACP composites will be evaluated for their physicochemical, mechanical properties and biological/cellular responses under conditions closely simulating a dynamic oral milieu. Newly designed materials are also expected to outperform the conventional Class V controls with respect to leachability of the unreacted monomers and polymerization shrinkage, while matching their mechanical performance and bonding properties. Successful completion of this application will yield a prototype(s) Class V composite(s) suitable for further testing in animal studies and/or in randomized clinical trials.
|Rahimi, Christopher; Rahimi, Benjamin; Padova, Dominic et al. (2018) Oral mucosa-on-a-chip to assess layer-specific responses to bacteria and dental materials. Biomicrofluidics 12:054106|
|Bienek, Diane R; Frukhtbeyn, Stanislav A; Giuseppetti, Anthony A et al. (2018) Antimicrobial Monomers for Polymeric Dental Restoratives: Cytotoxicity and Physicochemical Properties. J Funct Biomater 9:|
|Bienek, Diane R; Skrtic, Drago (2017) Utility of Amorphous Calcium Phosphate-Based Scaffolds in Dental/Biomedical Applications. Biointerface Res Appl Chem 7:1989-1994|
|Bienek, Diane R; Tutak, Wojtek; Skrtic, Drago (2017) Bioactive Polymeric Materials for Tissue Repair. J Funct Biomater 8:|
|Skrtic, Drago; Antonucci, Joseph M (2016) Polymeric dental composites based on remineralizing amorphous calcium phosphate fillers. Curr Trends Polym Sci 17:1-31|