Despite sufficiently high initial bond strengths exhibited by just about any contemporary dental restorative material, the tenacity of the bond can become progressively compromised over time. Reductions in bond strength are a result of mechanical and/or chemical insult degrading the substrate tissue, leading to bond fragility and, ultimately, restoration failure. This failure mechanism is particularly prevalent for class V restorations where the defect geometry both necessitates an enduring high bond strength to ensure longevity and results in persistent chemical insult owing to the proximity of the gingiva. To address this problem, we propose to engineer `anti-fragile' interfaces between composite dental restorative materials and the underlying tooth substrate. The clinical significance and innovative aspect of this research lies in the development of an adaptive interface through the use of engineered peptides that enable bond strengths to actually increase in response to insult. This enabling technology is expected to improve the longevity of class V dental restorations by having the restoration progressively bind with collagen exposed upon pH-mediated demineralization. The restorative materials will also bind to hydroxyapatite via a second set of peptides, thus they are affixed to both organic and inorganic phases of dentin. Inorganic, pH-buffering particles will be incorporated in the composite itself to mediate the local pH, delaying tissue loss owing to demineralization. Thus, we propose a dual materials-based approach to control the interface between a restoration and the tooth, ultimately increasing the longevity of the restoration. We will test the central hypothesis that incorporating tethering oligomers that bond to collagen and/or apatite on the tooth surface and functional groups on the composite resin will increase the bond strength over time and under acidic conditions. To test this central hypothesis, our specific aims and sub-hypotheses are to: 1. Develop oligomers bearing (i) dynamic covalent functional groups that, under reduced pH conditions, react with either the amine pendant groups of collagen-bound lysine residues or aldehyde and ketone groups resulting from post-translational lysine modification, and (ii) polymerizable pendant groups to covalently integrate dental restoratives with the substrate tissue. 2. Incorporate apatite-binding oligopeptides at the restoration/tissue interface to further improve restoration adhesion. 3. Synthesize self-buffering composites based on the incorporation of pH buffering inorganic nanoparticles that are able to act as localized pH buffers, mitigating chemical insult, and to test the biocompatibility of the materials systems developed in Aims 1-3. We will measure the interfacial bond strength, formation of marginal gaps, bulk physical properties and biocompatibility, with the primary outcome defining success being a bond strength superior to existing composites without peptide tethering, and biocompatibility equal to or superior to existing composites. In addition to the specific impact of the proposed work on restorative dentistry, our approach has much broader potential impact. The technologies proposed can be applied to any adhesion problem, including material- material, material-biologic, and biologic-biologic adhesion, and are therefore applicable to a wide variety of tissue engineering endeavors, including bone and dentin tissue engineering, tendon and ligament repair, and enamel formation.
This research involves the design and development of engineered, `anti-fragile' interfaces between composite dental restorative materials and the tooth substrate. A critical limitation of current dental restoratives is the long-term breakdown of the restoration/tooth bond. The clinical significance and innovative aspect of this research lies in the development of an adaptive interface through the use of engineered oligomers that enable bond strengths to actually increase in response to insult. This enabling technology will improve the longevity of class V dental restorations by having the restoration progressively binding with collagen exposed upon pH- mediated demineralization. The restorative materials will also bind to hydroxyapatite such that they are affixed to both organic and inorganic phases of the tooth. Inorganic, pH-buffering particles will be incorporated in the composite to mediate the local pH, delaying tissue loss owing to demineralization. The tenacity and longevity of the interfacial bond will be evaluated using standard mechanical and biological tests.
| Ramaraju, Harsha; Miller, Sharon J; Kohn, David H (2017) Dual-functioning peptides discovered by phage display increase the magnitude and specificity of BMSC attachment to mineralized biomaterials. Biomaterials 134:1-12 |
