Hyaluronic acid composite hydrogel with enhanced lubrication and controllable drug release for the mitigation of osteoarthritis

Excessive inflammation, overexpressed reactive oxygen species (ROS), degradation of the extracellular matrix, and high friction aggravate osteoarthritis (OA). Intra-articular injection for local drug delivery in the joint cavity enhances drug retention duration for OA treatment. Nevertheless, it remains a challenge to attenuate OA by thoroughly modulating the joint microenvironment, achieving controlled drug release, and enhancing lubrication. This study develops hyaluronic acid (HA) composite hydrogels, infused with gelatin microspheres containing a drug, utilizing dynamic interactions between phenylboronic acid and catechol to modulate the microenvironment by scavenging ROS, facilitating controlled drug release, and improving lubrication to mitigate OA. The composite hydrogels can be injected by intra-articular injection due to the shear-thinning properties, demonstrating broad ROS scavenging capacity and matrix metalloproteinase-9 responsive drug release. Both the in vitro and in vivo experiments prove the protective efficacy of the composite hydrogels against the degradation of cartilage matrix. Additionally, the hydrogels can offer efficient lubrication and effectively attenuate OA. Thus, the injectable HA composite hydrogels demonstrated potential in the management of OA.