Decoupling stiffness and toughness of self-healing hydrogels for complex tissue regeneration via 3D bioprinting

Abstract

Although polysaccharides are attractive biocompatible materials compared with synthetic polymers, most polysaccharide-based hydrogels exhibit suboptimal mechanical properties. In this study, we fabricated a hyaluronate (HA)-based self-healing hydrogel with enhanced toughness that can be used as a 3D bioink for complex tissue regeneration. We hypothesized that the incorporation of oxidation, aimed at minimizing the reduction in the molecular weight of HA, along with the introduction of a double network to the hydrogel, could facilitate the construction of 3D structures with decoupled stiffness and toughness. Various physicochemical properties of hydrogels comprising oxidized and hydrazide-modified HAs for potential use as bioinks were assessed. Bilayered constructs containing primary chondrocytes and osteoblasts were designed and fabricated using 3D printing to mimic the growth plate structure. Transplantation of the 3D-printed construct into a mouse model revealed the controlled differentiation stages of chondrocytes. This strategy for tailoring 3D scaffolds and addressing the limitations of polysaccharide-based hydrogels may hold promise for applications in the biomedical field, including the regeneration of complex tissues and organs.