Rational design of biomaterials for drug delivery and tissue engineering requires a fundamental understanding of the structure-property relationships in these materials, including diffusion through the medium, the mechanical properties, and thermodynamic transitions that may be exploited to produce environmentally responsive materials. Hydrogel biomaterials offer the unique advantages of responsive swelling and sol/gel transitions, injectability, and flexibility in loading with macromolecular drug therapies. Protein-based hydrogels are particularly attractive as biomaterials because of their biocompatibility, biodegradability, and inherent biofunctionality. A simple approach to produce physical protein gels employs protein triblock copolymers with leucine zipper endblocks to form physical crosslinks and flexible polyelectrolyte midblocks. Using both theory and experiment, this project will elucidate the fundamental structure-property relationships governing these gels. Protein polymers will be prepared using biosynthetic techniques to take advantage of the explicit sequence specificity offered in biological materials. The dynamical properties of these materials will be studied as a function of crosslink valency, molecular weight, chain flexibility, and crosslink strength to elucidate key structure-property relationships. A coarse-grained theoretical model will be developed and parameterized. Using input from the experiments, this model will be refined, and the predictions of the model will be used to guide the synthesis of gels with properties targeted at specific applications in tissue engineering or drug delivery. The coarse-xjrainingapproach employed will allow many of the results to be generalized beyond the specific experimental system, providing insight into the design principles of general hydrogel systems. Protein hydrogels are interesting biomaterials due to their similarity to human tissue, biodegradability, and the ease with which they can be modified to perform a biological function. This project will develop an understanding of how the protein sequence and gel structure affect the properties of protein hydrogels, allowing them to be optimized for drug delivery and tissue engineering.
| Satori, Chad P; Ramezani, Marzieh; Koopmeiners, Joseph S et al. (2017) Checkpoints for Preliminary Identification of Small Molecules found Enriched in Autophagosomes and Activated Mast Cell Secretions Analyzed by Comparative UPLC/MSe. Anal Methods 9:46-54 |
