One-Pot Approach to Synthesize Tough and Cell Adhesive Double-Network Hydrogels Consisting of Fully Synthetic Materials of Self-Assembling Peptide and Poly(ethylene glycol)

Hydrogels with a double network (DN) structure are compelling biomaterials, holding potential for use as artificial extracellular matrices. Generally, the DN approach imparts hydrogels with high mechanical strength and cell-adhesive properties. However, achieving this often demands a complex multistep process involving potentially hazardous free-radical polymerization, which can result in toxicity. This limits their broad biological applications. In this work, we introduce a straightforward yet biocompatible method to fabricate tough and cell-adhesive DN hydrogels using entirely synthetic materials: the self-assembling peptide (RADA16) and poly(ethylene glycol) (PEG). An in situ mixing of these components leads to the sequential formation of DN hydrogels─first through the self-assembly of the RADA16 peptide and then via chemical cross-linking between PEG molecules. Hydrogels produced this way exhibited up to a 10-fold increase in fracture energy, and cells seeded on their surfaces showcased good attachment. Our design underscores the efficacy of the DN approach and the promising applications of peptides in tissue engineering.