Biomimetic Semi-Flexible Hydrogel with Reduced Inflammation for Bone Defects

Engineered 3D scaffolds must be biomechanically capable to substitute injured tissues, and have typically been made of tissue-mimicking stiffness. However, this paradigm is shifting towards the understanding that the stiffness of scaffolds can be directly responded to by cells. Herein, we have designed a soft hydrogel to meet two criteria that can shift from soft to progressively hard tissue, similar to tissue development in nature. First, inspired by clotting of blood at the wound site, the goal is to achieve strong bonding with adjacent tissues through physical crosslinking of fibrinogen (FBG). Second, the hydrogel is needed mattress to dissipate energy such as existing collagen (COL) in the body. This scaffold promotes energy dissipation by strengthening the elastic and soft fibers of the FBG through COL to form a dense structure. As a crucial fundamental substrate, soft hydrogels initially induce rapid cell adhesion due to their soft surface. Sequentially, the cells increase to penetration inner part and make rigid themselves, and leading to bone formation. Furthermore, this hydrogel was composed of ECM-like tissue, which could reduce inflammation in the early stage. Therefore, our dual-function system provides a promising strategy for natural tissue-mimicking bone regeneration by reducing inflammation, and concurrently bridging defect area through harmonizing the newly assemble cells and ECMs.