Surface Engineering Strategies for Studying Human Mesenchymal Stem Cells (hMSCs).

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ID: MPS/DMR/BMAT(7623) 0906123 PI: Gopalan, Padma ORG: University of WisconsinTitle: Surface Engineering Strategies for Studying Human Mesenchymal Stem Cells (hMSCs)This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).INTELLECTUAL MERIT: This proposal describes a three-year plan of integrated research, education, and outreach on a biomaterial platform for studying human mesenchymal stem cells (hMSCs). It is proposed to develop model platforms that will allow for stable presentation of cell adhesion motifs over an extended time frame, to clearly address the hypothesis: ECM-derived cell adhesion ligands strongly influence osteogenic hMSC differentiation. The synthetic templates for studying cellular interactions, should meet multiple requirements such as: (a) presentation of multiple signals in optimized combinations on a bioinert background, which requires synthetic flexibility, (b) ability to apply to a range of planar and non-planar substrates, (c) stability over extended time period for long differentiating cells, and (d) the ability to spatially localize the signals. The last two requirements would extend the applicability of the template to biomedical implants and devices. UV-crosslinked thin-films (30-50nm) with 2-3 % of crosslinking will be examined. The intellectual impact of the proposed research is in exploiting the attributes of crosslinked thin-films such as exceptional stability, application to atypical substrates, chemical tailorability to be cytophobic or cytophilic, and photo-patternability for studying long differentiation processes. The specific tasks that will be undertaken towards this goal are: (a) Materials synthesis of a range of UV-crosslinkable copolymers based on polyethylene glycol copolymers containing a controlled distribution of photo-crosslinkable and ligand (biological signals) groups. (b) Evaluation of mechanical and chemical stability of the templates by a combination of surface characterization methods and fluorophore tagged peptides. (c) Study the cell adhesion, growth and differentiation in standard cell culture medium and cell culture medium containing pro-osteogenic supplements. (d) Evolve methodology to modify a variety of non planar substrates by dipcoating, microcontact printing and use of an ultrasonic microplotter. BROADER IMPACTS: The broader impact of the proposal will be developing a new class of biomaterials coatings with unique set of properties for stem cell studies. In order to clearly understand the effects of microenvironmental signals on stem cell behavior, there is a critical need for experimental systems that present specific signals, and complex signal combinations, to stem cells. Ultimately, this line of research may 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. The PI and co-Pi also propose to introduce interdisciplinary curriculum development through two courses, Polymeric Materials, based in Materials Science & Engineering, and Stem Cell Bioengineering, based in Biomedical Engineering. Ongoing educational outreach to the K-12 level will continue to develop hands-on exhibits for use in school settings with special attention to matching the K-12 Science Standards of the State of Wisconsin. The PI and co-PI will mentor female and underrepresented graduate and undergraduate students in their research laboratories.