Title: "Synthesis and Evaluation of Polymer Mosaics as Highly Tunable Biomaterials for Biomedical Applications"
Arturo Vegas, PhD – Chemistry (Advisor, Chair)
Joyce Wong, PhD – BME
Mark Grinstaff, PhD – BME
Tyrone Porter, PhD – ME
Nature is composed of an extensive assortment of nanomaterials that are highly organized and assembled from defined macromolecular structures. Proteins are quintessential examples of these nanomaterials with structural complexity and functional novelty. One hypothesis for how proteins evolved their complexity is based upon the shuffling and combination of hundreds of conserved regions or domains. Inspired by nature, various approaches such as polymerization induced self-assembly (PISA), single chain nanoparticles (SCNPs), and bio-hybrid materials have been developed to achieve controlled morphology, tunable dimensions, and diverse novel functionalities. Even though biomaterials are also composed of a diverse array of macromolecules and have been widely used in biomedical applications, each of these materials only include a small set of monomers that limit their structural complexity and utility. Therefore, there is a critical need to incorporate greater structural complexity and functionality to enable new technologies. To date, there have been no approaches to shuffle and organize different biomaterials into domains mimicking the way that nature assembles materials. To address this challenge, we hypothesize that arranging biomaterials into domain-structured single-chain polymers (polymer mosaics) will impart them with emergent physicochemical properties and novel functionalities, which can be controlled by domain composition and order. The arrangement can be achieved by tetrazine and trans-cyclooctene (TCO) mediated inverse electron demand Diels-Alder click reaction, which provides high rate constant to compensate for low polymer concentration and orthogonality to polymer identities. To test these hypotheses, we propose a method for fabricating polymer mosaics composed of biomaterials with complementary properties, stimulus responsive behaviors, and defined secondary structural elements. The successful development of polymer mosaics with defined structure and novel functionality can potentially impact the areas of controlled release systems and tissue engineering. The specific aims of this proposal are: (1) Develop self-assembled core-shell nanoparticles of Alginate/Polyethylene Glycol/ Poly (D, L-lactide) for controlled release systems; (2) Evaluate the influence of block length, ionic crosslinking strength, and domain component on the physicochemical and mechanical behaviors of polymer mosaics ; (3) Understand the impact of chirality on the assembly of polymer mosaics utilizing discrete secondary structural elements.