Development of Super-Lubricious Hydrogel Microspheres for the Treatment of Knee Osteoarthritis

Osteoarthritis (OA) significantly alters the microenvironment of the knee, increasing inflammation and reducing lubricity. Consequently, OA can result in debilitating pain that necessitates a total joint replacement. Here, we developed super-lubricious hydrogel microspheres to reduce friction and inflammation within the synovium. Hydrogel microspheres were fabricated using polyethylene glycol and subsequently coated with a custom-synthesized copolymer. This copolymer consisted of monomers of dopamine methacrylate (DMA), which provides the microspheres with strong attachment properties, and sulfobetaine methacrylate (SBMA), which provides lubrication due to its zwitterionic nature. The optimization of DMA:SBMA ratios, as well as the copolymers' arrangement (block vs. random copolymer), is currently underway to balance microsphere adhesion and lubricity. Microsphere lubricity was tested using a custom-built tribo-rheometer that enables the quantification of friction coefficients for small sample volumes (140 µL compared to 500 µL for standard tribology set-ups). Copolymer-coated microspheres demonstrated lower friction compared to uncoated microspheres, as well as the synovial fluid derived from patients with varying degrees of osteoarthritis or knee ligament tears. Additionally, the coated microspheres were shown to be injectable, allowing for facile in situ delivery. When injected intra-articularly into the knee capsule of healthy mice, the microspheres persisted for over 10 days and did not cause pain or interfere with daily mice activities. Our current work is focused on loading the microspheres with disease-modifying therapeutic molecules, such as platelet-rich plasma (PRP), and testing those in mice models of OA.