Dentin Biomodification for Optimization of Bioadhesive Dental Restorations

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SUMMARY The most conservative and common treatment of missing dental tissue is direct resin composite restoration. Its failure rate is high, lasting an average of 6 years. The primary reason for failure is the development of secondary caries. An estimated 50% of resin composite interventions replaces failed restorations, leading to a vicious restorative cycle with increasing complexity, poor prognosis for the tooth, and high treatment costs. Resin-based restorations rely on micro-mechanical adhesion to enamel and dentin structures. Dentin is of particular importance as it is the bulk of the tooth and tightly connected with the pulp tissue. It is well known that components of the dentin extracellular matrix play major roles in the formation and sustainability of the dentin-resin bonds. Bioinspired by natural dentin toughening mechanisms, our group identified refined mixtures and isolated proanthocyanidins (PACs), a 3D structurally diverse class of biosynthetic polyphenols that can mimic dentin natural processes. These molecules elicit enhancement to the mechanical properties and reduce matrix biodegradability, collectively termed dentin biomodification. Additionally, we have revealed that PACs can play multi-functional roles at the inherently wet dentin-resin interfaces. Therefore, PACs represent new biomaterials with promising impact in the broader field of restorative/reparative dentistry. Notably, the PAC sources of this project are renewable industrial waste and/or by-products, respectively, making them highly sustainable from both economic and environmental perspectives. The ultimate goal is to develop a mechanistically based and clinically feasible strategy to modulate permanent physico-mechanical properties of the dentin matrix, to create more stable dentin-resin bioadhesion, and thus increase the longevity of resin composite restorations. This will be accomplished by identifying features of specific molecules, ligand-PACs, that mediate stable biomodification and durable dentin-resin interfaces. More specifically, this project will define the structure activity relationships of ligand-PACs (a) to modulate the main components of dentin (extracellular matrix and mineral) sustainably; (b) to establish and optimize bioadhesion mechanisms at the dentin-PAC- resin interfaces; and (c) to tailor interfacial responses that directly affect performance and (pre-)clinical usage. The Specific Aims are: (Aim 1) Define distinct mechanisms of interactions of ligand-PACs with the extracellular matrix, mineral phase, and altered forms of dentin. (Aim 2) Elucidate and tailor ligand-PACs to produce robust biointerfaces. (Aim 3) Determine the stability of the tooth-PAC-resin interfaces in relevant microenvironments. The sustainable biomodification of the dental tissue will overcome clinical pitfalls associated with failure of tooth-resin interfaces, particularly dentin breakdown. The ultimate outcome is the development of a PAC-based intervention approach that can revolutionize dental restoration.