Dynamic, thermoresponsive control of physicomechanical properties of cell-laden hydrogel by multivalent elastin-like polypeptide crosslinker

Abstract

Hydrogels possess physicomechanical properties favorably suited as scaffolds to culture cells and tissues for biomedical applications, as their hydrated, elastic polymeric network can emulate natural extracellular matrix. In particular, their mechanical properties could be tuned to control various cell phenotypes. Conventional methods rely mostly on controlling the crosslinking density through adjusting the monomer and crosslinker concentrations. While effective, the range of resulting mechanical properties is still bound by the type and concentration which may adversely affect the diffusional properties. In this study, a new type of stimuli-responsive polymeric crosslinker based on elastin-like polypeptide (ELP) is introduced to more dynamically control the mechanical properties of hydrogels. ELP is conveniently produced by recombinant DNA technology, followed by conjugation of methacrylic groups to develop the ELP crosslinker. Since ELP undergoes phase transition driven by hydrophobic interaction above a critical temperature, usually within a physiological range, ELP-linked hydrogel undergoes thermoresponsive deswelling at physiological temperature of 37 degrees C, resulting in enhanced mechanical properties. The length of ELP and the degree of methacrylate substitution are varied to further expand the range of mechanical properties. Various phenotype of cells encapsulated in ELP-crosslinked hydrogels are explored in detail to analyze the effect of tunable mechanical properties.