Cartilage-binding coacervate with therapeutic payload delivery and biomimetic lubrication alleviates osteoarthritis by reducing joint friction and inflammation

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Abstract
Healthy articular cartilage maintains ultralow friction through the lipid/hyaluronic acid/lubricin complex lubrication layer, in which the zwitterionic lipids mediate lubrication and the hyaluronic acid and lubricin anchor to cartilage matrix. However, in osteoarthritis this lubrication system is progressively degraded, leading to increased cartilage wear and joint dysfunction. Therefore, early and lubrication-based intervention is urgently needed. Here we present biomimetic polyzwitterionic coacervates (pZCOs) that recapitulate both the lubrication and cartilage-binding functionalities of the natural boundary lubrication layer. pZCOs exhibit strong binding affinity to fibronectin, establish a stable and ultralow-friction lubrication layer on the cartilage surface, facilitate the sustained release of anti-inflammatory drugs, and preserve the viability and anti-inflammatory paracrine secretion of encapsulated mesenchymal stem cells. In both rat and mini-pig models of osteoarthritis, intra-articular administration of drug/MSC-laden pZCOs effectively reduces cartilage degradation, suppresses inflammation and promotes cartilage integrity, outperforming clinical hyaluronic acid lubricants in lubrication performance, in vivo retention and therapeutic efficacy. These findings highlight the translational potential of engineered biomimetic coacervates as next-generation joint lubricants for integrated management of osteoarthritis.

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