Substrate Independent, Spatially Resolved, Stable Polymer Coatings for Studying Human Mesenchymal Stem Cells (hMSCs)

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This award by the Biomaterials program in the Division of Materials Research is a three-year plan of integrated research, education, and outreach on a polymeric coating for studying human mesenchymal stem cells (hMSCs). This award is cofunded by the Polymer program in the Division of Materials Research. Earlier studies strongly indicate that hMSC phenotype is strongly influenced by ligands derived from the natural cellular microenvironment, including cell adhesion peptides, heparin-binding peptides, and growth factor-mimetic peptides. This proposal is to develop polymer coatings based on copolymers of poly(ethylene glycol) with at most 10% of crosslinkable groups, which can be crosslinked into 30 nm mats for immobilization of peptides. These mats are chemically-defined for stable presentation of two putative pro-osteogenic peptides over an extended timeframe, and to explore in depth the effects on hMSC differentiation into osteoblasts. These polymer coatings with peptides present a stable cytophobic slate, and hence one can truly investigate the effect of the relevant peptides on hMSCs during the entire time course of osteogenic differentiation. Importantly, these coatings are thin films that can be applied to virtually any underlying substrate, which will lead to broad impact on cell culture studies and future design of biomedical devices. Because of the thin-film nature, the proposed use of X-ray photoelectron spectroscopy will quantify precisely the peptides presented on the polymer coatings. Further, this proposal will study the first systematic analysis of chemically defined, nanometer-scale presentation of a growth factor-receptor binding ligand, and it may lead to broad impact in view of the importance of receptor dimerization/clustering in virtually all growth factor signaling systems. The technological broader impact of this proposal would be in developing a new class of ultra-thin biomaterial coatings with unique set of properties for stem cell growth. In order to clearly understand the effects of micro environmental signals on stem cell behavior, there is a critical need for experimental systems that present specific signals, and complex signal combinations, to stem cells. The proposed platform may lead to widespread use of the proposed approaches by cell biologists in general. Ultimately, this line of research could result in identification of signals that promote lineage-specific stem cell differentiation, leading to development and optimization of substrates that promote stem cell differentiation in vitro and in vivo. More generally, the proposed adaptable and chemically tailorable thin films would be applicable to a broad range of fundamental questions in cell biology in which stable, controlled presentation of peptide ligands is desirable. As part of this grant, this project will: 1) develop Interdisciplinary Curriculum Development of two courses in two departments, one based in Materials Science & Engineering, and the second one based in Biomedical Engineering; 2) carry out dissemination and outreach activities by the development of hands-on exhibits on Stem Cells and Tissue Engineering that would provide case study materials for a Science and Social Media course; and 3) recruit and mentor female and underrepresented minority graduate and undergraduate students in research activities.