Temperature‐sensitive Hydrogels in Tissue Engineering

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 ). 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, and protease degradation. Ultimately, we intend to use these tunable hydrogels to establish design rules for engineering tissue regeneration in vivo . As a first step in this program, we have exploited the thermo‐responsiveness of N‐isopropylacrylamide (NIPAAm) to synthesize copolymer hydrogels with acrylic acid (AAc) [ p(NIPAAm‐ co ‐AAc) ] to serve as model injectable hydrogels for engineering tissue regeneration. 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. This system allows for easy synthesis of admixtures of peptide sequences while independently maintaining the mechanical properties of the matrix. Therefore, studies addressing the effect of ligand type and density, in the context of matrices with various mechanical properties, can be easily performed. We propose a general strategy based upon our novel artificial ECMs that will provide: 1) a foundation for local cell development from undifferentiated satellite stem cells; 2) enhance angiogenesis and host cell infiltration; and, 3) promote tissue regeneration in a defect model. Examples relevant to regeneration of bone and ischemic myocardium will be discussed.