Injectable Biomimetic Lubricant‐PRP Hydrogel with Synergistic Lubrication from In/Ex‐Sources for Cartilage Regeneration in Rabbits

Abstract Cartilage regeneration remains a clinical challenge, as existing treatments (including pharmacological and physiological treatments) only alleviate symptoms. This work proposes a novel strategy of in/ex‐source synergistic lubrication and develops an injectable bioactive hydrogel that synergistically lubricates articular cartilage and promotes cartilage regenerative repair by providing immediate exogenous biomimetic lubricant and promoting endogenous synovial fluid secretion. The hydrogel, composed of a biomimetic lubricant (HDPA) and platelet‐rich‐plasma (PRP), rapidly forms a gel via biological cross‐linking, offering both physical lubrication and bioremediation functions. It significantly reduces cartilage friction, facilitates cell proliferation, migration or recruitment, and promotes their chondrogenic differentiation. Additionally, it stimulates synovial fibroblasts to secrete endogenous hyaluronic acid, achieving in/ex‐source lubrication. RNA‐seq reveals suppression of pro‐inflammatory NF‐κB/IL‐1 pathways and activation of TGF‐β signaling, promoting hyaluronic acid (HA) synthesis and ECM remodeling. In a rabbit model, the hydrogel induces hyaline cartilage regeneration and achieves the optimal healing effect, outperforming controls and single treatments. The approach of combining a biomimetic lubricant with PRP, therefore, is potentially useful for the treatment of osteoarthritis.