The long-term objective of this research is to develop materials that promote regeneration of bony tissues for reconstructive dental and craniofacial applications. The overall hypothesis is that the fate of stem cells within an engineered tissue, and the resulting structure and function of the engineered tissue can be regulated by the presentation of appropriate signals in the microenvironment of the cells. Over the past several years, it has become clear that the mechanical properties and, in particular, the elastic modulus of the adhesion substrate, regulate stem cell differentiation. Work to date in the field of mechanotransduction has focused on purely elastic materials, but natural extracellular matrices (ECMs) are, in contrast, typically viscoelastic and exhibit complex, time-dependent mechanical behavior, as indicated by their creep and stress relaxation.
In collaboration with CECT, this project will work towards the fabrication of natural and hybrid hydrogels (alginate, alginate - acrylamide hybrids, or ECM derived) that display a range of stress relaxation times, and its impact on mesenchymal stem cell (MSC) adhesion, proliferation, and differentiation. Using the biofabrication resources within CECT, we will fabricate composite structures in which a printed framework of a rigid, biodegradable polymer [poly(lactide-co- glycolide)] provides the bulk mechanical properties, while a hydrogel subsequently infiltrates the framework and controls the cells’ differentiation and tissue regeneration abilities.
Images courtesy TEBL (UMD)