Generation of cell-instructive collagen gels through thermodynamic control

Abstract

Recent studies have demonstrated the usefulness of three-dimensional hydrogel scaffolds for cell instruction. However, the control of gel architectures in cell-friendly conditions remains a challenge. Here, we report a novel method to generate unique three-dimensional collagen gel structures for the modulation of cell phenotypes. This was achieved by directing collagen self-assembly with unreactive hydrophilic polyethylene glycol (PEG) chains. Our approach allowed the fiber sizes and mechanics of three-dimensional collagen gels to be readily controlled. It also enabled the recapitulation of distinctive structures such as large perimysial collagen cables. Through different experiments, we elucidated the underlying mechanism for this PEG-mediated thermodynamic regulation of gel structure. We further used these cell-instructive three-dimensional gels to bring about pronounced morphological changes in encapsulated fibroblasts and their activation to form contractile bundles. Overall, our platform fills a gap in the existing array of collagen scaffolds and can potentially be adapted to a variety of self-assembling systems. © 2013 American Chemical Society.