Mechanically Reinforced Gelatin Hydrogels by Introducing Slidable Supramolecular Cross-Linkers

Tough mechanical properties are generally required for tissue substitutes used in regeneration of damaged tissue, as these substitutes must be able to withstand the external physical force caused by stretching. Gelatin, a biopolymer derived from collagen, is a biocompatible and cell adhesive material, and is thus widely utilized as a component of biomaterials. However, the application of gelatin hydrogels as a tissue substitute is limited owing to their insufficient mechanical properties. Chemical cross-linking is a promising method to improve the mechanical properties of hydrogels. We examined the potential of the chemical cross-linking of gelatin hydrogels with carboxy-group-modified polyrotaxanes (PRXs), a supramolecular polymer comprising a poly(ethylene glycol) chain threaded into the cavity of alpha-cyclodextrins (alpha-CDs), to improve mechanical properties such as stretchability and toughness. Cross-linking gelatin hydrogels with threading alpha-CDs in PRXs could allow for freely mobile cross-linking points to potentially improve the mechanical properties. Indeed, the stretchability and toughness of gelatin hydrogels cross-linked with PRXs were slightly higher than those of the hydrogels with the conventional chemical cross-linkers 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS). In addition, the hysteresis loss of gelatin hydrogels cross-linked with PRXs after repeated stretching and relaxation cycles in a hydrated state was remarkably improved in comparison with that of conventional cross-linked hydrogels. It is considered that the freely mobile cross-linking points of gelatin hydrogels cross-linked with PRXs attenuates the stress concentration. Accordingly, gelatin hydrogels cross-linked with PRXs would provide excellent mechanical properties as biocompatible tissue substitutes exposed to a continuous external physical force.