An interpenetrating polymer network hydrogel with biodegradability through controlling self-assembling peptide behavior with hydrolyzable cross-linking networks

Abstract Hydrogels are used as cell culture scaffolds for tissue engineering and regeneration. These hydrogel designs are inevitably complicated because favorable scaffolds should have stiffness to sustain alignment of the cells and mimic the structure of the extracellular matrix (ECM) in the targeted tissue. However, the incorporation of biodegradability, which is an essential property for practical applications, into complex hydrogels is not easily attained. Herein, we established a new concept for constructing biodegradable hydrogels with an interpenetrating polymer network (IPN) structure, composed of a covalent cross-linked network and peptide self-assembling networks, to solve this dilemma of selecting between the complicated structure and facile biodegradability. Assuming that the diffusion of the self-assembled peptides out of the IPN hydrogel would be facilitated by the disappearance of the covalent cross-linked networks, we designed an IPN hydrogel with chitosan cross-linked with poly(ethylene glycol)-block-poly( dl -lactide)-block-poly(ethylene glycol) as the covalent cross-linked networks with hydrolysis properties and RADA16 peptides as the self-assembling networks. This IPN hydrogel showed overall degradation, based on hydrolysis of the poly( dl -lactide) domain, and was more effective as a scaffold for culturing chondrocytes to form articular cartilage tissues compared with the IPN hydrogel without the poly( dl -lactide) domain, likely owing to the promotion of ECM deposition. These results verified our strategy of constructing a hydrogel with a complicated, but biodegradable, structure.