Proliferating Cells Encapsulated in Extracellular Matrix-Like Peptide Scaffolds Dynamically Change the Mechanical Properties of the Scaffold

Abstract

The extracellular matrix, or ECM, is a three-dimensional network that serves as a structural scaffold for tissue construction. To do so, cells need to attach, proliferate, self-organize, and coordinate biochemical deposition across multiple length and time scales. Hydrogels have been utilized as biomaterials because their chemical and mechanical properties can be designed to mimic those of native ECMs. Short, synthetic, amphiphilic peptides have been used to design scaffolds for tissue engineering because the peptides self-assemble in water and are easy to tune. To date, hydrogels for tissue engineering have typically sacrificed one or more crucial properties in favor of improving others, since nearly all chemical and mechanical properties within a hydrogel are interdependent. The focus of this research is to study the mechanical tunability and viability of ultrashort peptide hydrogels derived from naturally occurring amino acids (IIZR, IIZK, and IZZK), such that ideal concentrations of each peptide can be configured to mimic the mechanical properties of native ECMs for human dermal fibroblasts (HDFns) and primary cortical neurons (CNs). Our results show that IIZR, IIZK, and IZZK hydrogel scaffolds are good candidates for these cell types because their stiffness, elasticity, and biocompatibility are commensurate with those of these cells’ native ECMs. As evidence, the stiffness of the materials generally increased with HDFns across all concentrations, except for 2mg/ml. In particular, HDFns favored hydrogels consisting of higher peptide concentrations, resulting in greater elasticity and higher stiffness. IIZR hydrogels were also well-suited for both HDFns and CNs, which could have been due to the peptides’ positively charged R groups that can facilitate cell adhesion via electrostatics.