A shear-responsive and lubricating hyaluronic acid-chondroitin sulfate-decellularized matrix hydrogel for articular cartilage regeneration

The high-dynamic, high-loading environment in the joint cavity puts urgent demands on the cartilage regenerative materials with shear responsiveness and lubrication. Here, a new type of injectable hydrogel composed of oxidized hyaluronic acid (OHA), adipic dihydrazide-grafted hyaluronic acid (HA-ADH), oxidized chondroitin sulfate (OChs), and decellularized extracellular matrix methacrylate (dECMMA) was fabricated. The aldehyde groups in OHA and OChs reacted with the amino groups in HA-ADH to form a dynamic hydrogel, which was then covalently crosslinked with dECMMA to create a dual-crosslinked hydrogel with sufficient mechanical strength. This hydrogel possesses injectability and self-healing capabilities, making it suitable for use in the dynamic and high-frequency loading environment of joint cartilage. dECMMA fibers in this hydrogel could be oriented and aligned under certain shear forces, together with the biopolymers, giving the hydrogel lubricity and low strain-liquid transition properties that do not interfere with the daily mobility of the joint. In vitro and in vivo experiments showed that the hydrogel has sufficient tissue adhesion and excellent biocompatibility, promotes chondrocyte migration, and induces stem cell differentiation. The animal experiments demonstrated that the hydrogel promoted cartilage repair, and the lubricating effect of the newborn cartilage was close to that of normal cartilage.