CAREER: Development of a Multifunctional Polyester Platform and its Evaluation as an Instructive Matrix for Osteoblast Differentiation

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Non-technical Abstract: This CAREER Award by the Biomaterials program in the Division of Materials Research, and co-funded by the Biomedical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems (ENG/CBET) to the University of Akron is to develop a modular multifunctional polyester platform with peptide-like functional groups to be used as a matrix for stem cell differentiation. Products derived from polymeric materials are an integral part of modern life and polymer science has addressed several technological challenges. In addition to their extensive use as commodity and engineering materials, polymers are also widely used in the biomedical field to make implants, sutures, medical catheters, wound healing products etc. In spite of such extensive use, the design and performance of such synthetic materials lags far behind in their ability to match the performance of natural materials such as collagen in providing the functional cues necessary for optimum biological outcomes, such as in wound healing or precise growth and maturation of new tissue. The project will identify the key differences between natural materials such as collagen and widely used synthetic materials and offers a bottom-up design of a synthetic polymeric material platform. This modular synthetic polymer system, when fully developed, will have the physical and biological properties that would enable their use in several biomedical applications such as for differentiation of stem cells, as antimicrobials and for drug/protein delivery. This CAREER award facilitates the training of the next generation of scientists in STEM fields and provides fundamental training at the interface of chemistry, materials science and biology. The award specifically provides research opportunities for high school, undergraduate and graduate students. Socially and economically disadvantaged students from local high schools will be mentored through this program. In addition a select group of high school students with strong credentials will have the opportunity to engage in cutting edge research. In addition, the award enables to create a suite of freely available online educational videos describing the fundamental principles of polymer science.Technical Abstract: The key transmitter of information between cells and their surroundings is the extracellular matrix (ECM) and this information is processed by specific binding and signaling events between cells and the components of the ECM. Although synthetic biomaterials are being explored for an increasing number of clinical biomedical needs, the ability of current biomaterials to provide the required specificity in binding and signaling is still in its infancy due to the complexity in balancing the material parameters of functionality, reaction feasibility, degradability, hydrophilicity etc. The award will support the development of a new pendant functionalized polyester system which aims to provide the advantages of functionality and specificity as seen in peptides and proteins while also having the advantages of synthetic reproducibility and scalability that synthetic materials provide. As an illustrative case study, these multifunctional polyesters will be investigated as an instructive matrix for osteoblast differentiation with the aim of correlating the chemical profile of the multifunctional polyester system with stem cell proliferation and differentiation. Such a modular synthetic platform with the ability to precisely vary the polymer composition will be useful in several biomedical applications such as drug/protein delivery, self-assembled systems, multi-valent inhibitors and as antimicrobial agents. Students engaged in this research will work at the interface of chemistry, materials science and cell biology and will also have the opportunity to understand how their research addresses fundamental needs in the biomedical sciences.