Matrix metalloproteinase-sensitive poly(ethylene glycol)/peptide hydrogels as an interactive platform conducive to cell proliferation during 3D cell culture

The response of extracellular matrix (ECM) to dynamic cell signals is of great significance for the regulation of cell behavior. In the present study, we prepared a type of matrix metalloproteinase (MMP)-sensitive degradable hydrogels (MSDHs) via the catalyst-free o-phthalaldehyde (OPA)/amine cross-linking reaction between o-phthalaldehyde-grafted four-arm poly(ethylene glycol) (4aPEG-OPA) and an MMP-sensitive degradable peptide. The gelation rates and storage moduli of MSDHs and the MMP-insensitive hydrogels (MIHs) based on an MMP-insensitive scramble peptide were comparable and dependent on the concentrations of precursor polymers. MSDHs were degradable while MIHs were stable in the presence of proteinase in vitro. The degradation of MSDHs was obviously faster than that of MIHs after subcutaneous injection into rats. In addition, both types of poly(ethylene glycol)/peptide hydrogels displayed excellent cytocompatibility in vitro, and showed good histocompatibility in vivo in the subcutaneous layer of rats. Furthermore, the proliferation of several MMP-expressing cell lines including MDA-MB-231 cells within MSDHs was obviously faster than that in MIHs, indicating the influence of metabolism-mediated scaffold degradation on the cell proliferation. This study provides a new biocompatible and biodegradable 3D cell culture interactive platform for regulation of cell behavior.