Functionalized peptide hydrogels as tunable extracellular matrix mimics for biological applications

Abstract

The development of tailorable and biocompatible three-dimensional (3D) substrates or molecular networks that reliably mimic the extracellular matrix (ECM) and influence cell behavior and growth in vitro is of increasing interest for cell-based applications in the field of tissue engineering and regenerative medicine. In this context, we present a novel coiled coil-based peptide that self-assembles into a 3D-alpha-helical fibril network and functions as a self-supporting hydrogel. By functionalizing distinct coiled-coil peptides with cellular binding motifs or carbohydrate ligands (mannose), and by utilizing the multivalency and modularity of coiled-coil assemblies, tailored artificial ECMs are obtained. Fibrillar network and ligand density, as well as ligand composition can readily be adjusted by changes in water content or peptide concentrations, respectively. Mesoscopic structure of these networks was assessed by rheology and small-angle neutron scattering experiments. Initial cell viability studies using NIH/3T3 cells showed comparable or even superior cell viability using the presented artificial ECMs, compared to commercially available 3D-cell culture scaffold Matrigel. The herein reported approach presents a reliable (low batch-to-batch variation) and modular pathway toward biocompatible and tailored artificial ECMs.