Control of cell function with tunable hydrogel networks.
A critical problem limiting the field of tissue engineering is the lack of engineering design rules to guide the synthesis and fabrication of artificial extracellular matrices (ECMs) or scaffolds. To address this issue, we have created artificial ECMs that are environmentally responsive and tunable with respect to mechanical properties (e.g. G*), biological ligands, tissue adhesion, and protease degradation. Our current approach is to create modular hydrogel ECMs where different properties of the matrix can be manipulated independently, thus creating a system where parametric analysis of the effect of hydrogel properties on cell proliferation and differentiation is possible. For example, we have synthesized and characterized the physical properties of semi-interpenetrating polymer networks (sIPNs) consisting of linear polyacrylic acid (pAAc) chains within a thermo-responsive N-isopropylacrylamide-co-acrylic acid network [p(NIPAAm-co-AAc)]. Studies addressing the effect of RGD ligand type and density, in the context of matrices with various mechanical properties, have indicated that G*, RGD density, and protease cross-linkers are critical for rat calvarial osteoblast adhesion and proliferation. These peptide-modified P(NIPAAm-CO-AAc) hydrogels allow for easy control of the mechanical and chemical properties of the matrix, allowing parametric analysis of the effect of these properties on cell behavior in vitro and tissue development in vivo.
Healy
Kevin E
KE