Chemically- and mechanically-tunable porated polyethylene glycol gels for leukocyte integrin independent and dependent chemotaxis

Abstract

The extracellular matrix (ECM) is a highly complex mixture of protein, proteoglycans and growth factors that biochemically and mechanically regulates leukocyte migration during inflammation. Perturbations in ECM composition and mechanical properties are associated with the pathogenesis of chronic inflammatory diseases ranging from asthma to diabetes. The limited availability of in vitro models of human ECM has impeded inflammatory research, as current methods rely heavily on polycarbonate transwells and glass coverslips, which cannot accurately replicate the combined mechanical and biochemical properties of human ECM. Polyethylene glycol (PEG) hydrogels offer a highly tunable substrate, with respect to both mechanical properties (as a function of molecular weight) and protein conjugation; unmodified PEG, however, cannot be used for leukocyte migration studies due to its impenetrable pore networks. We present a modifi ed PEG membrane in which hydrogel pore size, pore density, mechanical stiffness, and protein presentation can be easily controlled to mimic various human ECM, providing a new technology for investigating leukocyte recruitment.