Platelet-Rich Plasma-Loaded Super-Lubricious Microgels for Knee Osteoarthritis Treatment

Knee osteoarthritis is a debilitating joint disease that impacts millions of people in the United States, with 1 in 2 people developing knee osteoarthritis by age 85. Available clinical treatments focus almost exclusively on the alleviation of pain without disease modifying effects. Consequently, OA progresses to an end-stage disease where total joint replacement is the only solution. Sustained delivery of platelet-rich-plasma (PRP) is a potentially transformative therapy for knee post-traumatic osteoarthritis (PTOA). PRP therapy is a method for collecting and concentrating platelets for the purpose of activating and releasing their 300+ bioactive molecules – proteins and lipids, which are critical to tissue regeneration and cellular recruitment. PRP has shown efficacy in accelerating chondrocyte proliferation and matrix production and resolving inflammation in vitro. Here, we aimed to fabricate dual-action injectable microgels that provide joint lubrication and sustained intra-articular delivery of platelet-rich plasma (PRP) for the treatment of knee PTOA. Fabrication of polyethylene glycol microgels, crosslinked via Michael-type addition, was achieved using electrospraying and microfluidics, forming tunable, biocompatible, and slowly degradable microspheres of diameter ∼100 μm. To enhance the lubricity of the microspheres, we synthesized a super-lubricious copolymer poly (dopamine methacrylamide-to-sulfobetaine methacrylate) poly(DMA-SBMA) as confirmed by 1H NMR. The copolymer was dip-coated onto the microspheres and mechanical properties, including coefficient of friction and viscosity, of coated and uncoated microspheres were tested using a custom tribo-rheology setup. Our results indicated that coated microgels had better lubrication compared to all other conditions, including uncoated microgels and synovial fluid from both OA and non-OA patients. Current work is focused on characterizing the properties of the resulting PRP-loaded PEG microspheres, including swelling, modulus, degradation, and protein release, as a function of PRP loading and preparation. Future directions include evaluating the effectiveness of intra-articular delivery of PRP-loaded superlubricious PEG microgels in a mouse model of PTOA. Ultimately, we present an injectable, superlubricious, sustained-release PRP delivery device, which will aid in preventing and treating knee PTOA. This research was supported by NIAMS/NIH under award number R01 AR081270-01A1: "Development of Injectable Super-Lubricious Microgels for Sustained Release of Platelet-Rich Plasma to Treat Post-Traumatic Osteoarthritis"