(615c) Control of Adult Stem Cells with Polyurethane Gel Matrix

Control of stem cell fate in tissue engineering application is important for effective and functional tissue regeneration. Extracellular matrix provides structural and functional cues in a highly synchronized fashion to stem cells for controlling the cellular processes and cell fate. Synthetic matrices are designed to induce similar interactions between stem cell and microenvironment which can effectively guide stem cells with spatial and temporal control. Biocompatible and biodegradable polyurethanes with segmental composition can be designed as gel with nanostructured phases due to the presence of ‘soft’ and ‘hard’ segments. By tuning the structure and composition of polyurethanes, the inter- and intra-segmental interactions can be modulated to control the polyurethanes into gel like structure. We have designed polyurethanes which forms gel through physicochemical interactions. Specifically, degradable peptide-based polyurethanes were synthesized and their interactions with adult stem cells were examined in 2-D substrate and 3-D environment. We examined the effect of polyurethane gel structure by varying the soft and hard segment. Soft segment of the polyurethanes were altered by using polyethylene glycol of different molecular weight and hard segment was designed from aliphatic diisocyanate with dipeptide chain extender. Our results shows that the composition of polyurethane chains with segments induce specific gel structure. Thus, by controlling the segmental architecture of polyurethanes, morphology of the gels were controlled to provide signals to stem cells. Interaction of bone marrow derived mesenchymal stem cells (MSCs) with the polyurethane gels shows specific dependence of the polyurethane structure and gel morphology. MSCs interacted with the different segments of polyurethane gels to present distinct cellular structure and behavior. Specifically, cell adhesion, aggregation, cellular structure and morphology were influenced by the polyurethane gel matrix. Interaction of MSCs with polyurethane reveals that segmental composition and gel morphology of polyurethanes influences the cell function and behavior which can control the fate of MSCs, particularly the differentiation of the stem cells. Biosynthetic activities of MSCs within the polyurethane gels were modulated to produce extracellular material leading to formation of tissue like structure. This study indicates that molecular engineering of polyurethane gel provide exquisite control of stem cell behavior. Thus, controlling cell-material interactions with these matrices can modulate tissue regeneration.