Bioinspired semi-flexible hydrogel with anti-inflammatory potential for natural tissue-mimicking bone regeneration

Three-dimensional (3D) scaffolds are typically created to replace damaged tissues and mimic the stiffness of the target tissue. It is now well established that cells respond to the stiffness of these scaffolds. In this study, we developed a semi-flexible hydrogel to mimic natural tissue and facilitate bone regeneration. The hydrogel was designed to transition gradually from soft to hard, resembling the stiffness of the target tissue. We achieved strong bonding with adjacent tissues by crosslinking fibrinogen (FBG), inspired by blood clotting at wound sites. Additionally, we utilized the mechanism of collagen (COL) to create a hydrogel that consumes energy and changes its internal state with body temperature. The composite hydrogel promoted energy dissipation by strengthening the elastic fibers of FBG through COL, forming a dense structure. The hydrogel's hydrophilic surface initially facilitated rapid cell adhesion, and as cells penetrated the inner part, they became rigid, contributing to bone tissue formation. Furthermore, the modified hydrogel's stiffness and surface affinity reduced inflammation during early stages of regeneration. Overall, our bioinspired semi-flexible hydrogel offers a promising strategy for mimicking natural tissue, reducing inflammation, and bridging defects during bone regeneration.