Chronic soft tissue oral wounds (e.g., Mucositis, aphthous stomatitis and periodontal disease) can be very painful and often are to develop a simple to apply polymeric barrier for the enhanced healing of these oral wounds. It is hypothesized that by rinsing the oral cavity with an aqueous polymeric solution, which can self assemble at the site of injury via fibrin targeting, it is possible to form a barrier that act as a platform for the sustained antioxidant therapy improving wound healing by suppressing chronic inflammation. In this project we propose to synthesize In-situ self assembled, layer by layer polymers films providing a protective barrier and a platform for future delivery of antioxidants for the treatment of local oxidative stress mediated tissue damage thereby reducing healing time improving a wide variety of oral repair and regeneration therapies. Functionalized polymers of Poly(ethylene glycol)-g-poly(methacrylic acid) and poly(methacrylic acid) will be synthesized and systematically evaluated to determine identify key parameters in the layer by layer barrier assembly. These polymers will use fibrin targeting via peptide modification, and biotin-streptavidin binding for layer by layer assembly. The biochemical stability of the barriers in the presence of human saliva will be tested using radiotracing. Mechanical barrier stability will be tested using a static load and cyclic contact mechanical model. Key parameters affecting barrier strength and targeting (e.g. polymer MW, number of layers, degree of target moiety functionalization) will be identified using a statistical design approach.
Specific Aims : 1.) Design and synthesis of layer-by-layer barrier assemblies. 2.) In vitro evaluation of layer-by-layer barrier stability.

Public Health Relevance

This project's goal is to develop a targetable polymer system which can be used to form an easy to apply self assembled barrier for the treatment of oral wounds and sores. Through a series of simple mouth rinses using complementary polymer solutions, a strong persistent barrier which can be loaded with drugs to accelerate healing times can be formed. It is believed that these barriers will be useful in treating patients with extreme cases of oral sores such as Mucositis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
5R03DE019496-02
Application #
7933998
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Drummond, James
Project Start
2009-09-17
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$110,364
Indirect Cost
Name
University of Kentucky
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Authimoolam, Sundar P; Lakes, Andrew L; Puleo, David A et al. (2016) Layer-by-Layers of Polymeric Micelles as a Biomimetic Drug-Releasing Network. Macromol Biosci 16:242-54
Authimoolam, Sundar P; Vasilakes, Andrew L; Shah, Nihar M et al. (2014) Synthetic oral mucin mimic from polymer micelle networks. Biomacromolecules 15:3099-111
Authimoolam, Sundar P; Puleo, David A; Dziubla, Thomas D (2013) Affinity based multilayered polymeric self-assemblies for oral wound applications. Adv Healthc Mater 2:983-92
Medley, John M; Kaplan, Eugene; Oz, Helieh S et al. (2011) Fibrin-targeted block copolymers for the prevention of postsurgical adhesions. J Biomed Mater Res B Appl Biomater 99:102-10