Highly regulated signals in the stem cell microenvironment, such as growth factor presentation and concentration, matrix stiffness, and ligand adhesion density have been implicated in modulating stem cell proliferation and maturation. Therefore, it is desirable to have independent control over both the biochemical and mechanical cues presented to cells to analyze their relative and combined effects on stem cell function. Accordingly, we have developed synthetic hydrogels to assess the effects of adhesion ligand presentation and material moduli spanning physiologically relevant ranges (10 to 10,000 Pa) on stem cell function. Employing these soft materials, we have demonstrated that the mechanical and biochemical properties of a stem cell microenvironment can be tuned to regulate the self-renewal and differentiation of different types of stem cells including human embryonic, neural, and mesenchymal stem cells. We have further modified these tunable biomimetic hydrogels with matrix metalloproteinase labile crosslinkers (e.g. MMP-2, 9 &13), to be used as an assistive microenvironment for transplantation of stem cells into diseased or damaged tissue such as the infracted myocardium. We hypothesize that injectable bioinspired hydrogels, designed with a range of mechanical and biological properties, will yield material-dependent improvements in cardiac function post myocardial infarction. Injection of cells alone created a transient improvement in LV function that declined over time, while the hydrogel without cells experienced a gradual increase in cardiac function and resulted in the highest LV function at 6 weeks. The bioinspired hydrogel succeeded in both mechanically supporting the injured myocardium and modestly enhancing donor cell survival. This bioinspired hydrogel system also provides a foundation for systematic development of �pro-survival� microenvironments for cell transplantation and has the potential to improve the long-term results of cardiac therapies.

Bioinspired soft materials to direct stem cell function and tissue regeneration

245th National Meeting (2013)

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