(E-189) Synthesis and optimization of poly(DMA-co-SBMA) polymer as a lubricous coating for microgels: Towards Application in the Treatment of Knee Osteoarthritis

Introduction: Knee osteoarthritis is a common orthopedic condition characterized by chronic debilitating pain and loss of function in the joints. It is estimated that 1 in 2 people will develop knee osteoarthritis by age 85. A key feature of osteoarthritis is compromised lubrication and mechanical properties driven by chemical changes in the synovial fluid. Available clinical treatments focus predominantly on alleviation of pain without addressing the underlying cause. Other injectable biotherapies have been developed to reduce inflammation but do not restore the mechanical properties of osteoarthritic joints and may be rapidly cleared from the synovial joint. Hydrogels have emerged as an approach to address these challenges. By tuning hydrogel swelling, biodegradation, and stiffness, the mechanical properties may be modulated to appropriately provide mechanical support in osteoarthritic joints and provide a depot from which therapeutics are released. This combinatorial approach of drug eluting hydrogels that provide mechanical support and lubrication, provides for dual treatment of osteoarthritic symptoms, without the need for complex or invasive surgeries. Here, polyethylene glycol (PEG) hydrogel microspheres were fabricated to provide mechanical support and serve as a sustained biomolecule delivery device. Hydrogel microspheres were coated with a super-lubricious copolymer to further enhance hydrogel lubricity and treatment effectiveness.

Materials and Methods: Polyethylene glycol (PEG) microspheres with diameter 5-40 microns were fabricated via aqueous two-phase separation (ATPS) and subsequently dip-coated in a copolymer consisting of adhesive dopamine methacrylamide (DMA) and super-lubricious zwitterionic sulfobetaine methacrylate (SBMA) monomers, forming a poly(DMA-co-SMBA) coating. Nuclear magnetic resonance (NMR) and Fourier Transform Infrared Spectroscopy (FTIR), spectroscopy (UV-vis) and fluorescent imaging were used to confirm successful coating of PEG microspheres with the lubricious copolymer. Molar ratios of DMA and SBMA were modulated to determine the effect on hydrogel microsphere lubricity. Hydrogel microspheres underwent a battery of rheological characterizations to determine various mechanical properties, including storage and loss moduli (G’ and G”), microsphere slurry viscosity and injectability, and coefficient of friction (COF). Coated microspheres were compared to uncoated PEG microspheres, as well as patient derived synovial fluid samples in the absence and presence of osteoarthritis. Furthermore, hydrogel microsphere degradation and swelling properties were measured as a function of copolymer coating. Bulk release studies of platelet-rich plasma (PRP) were performed to observe the effect of copolymer coating and PEG hydrogel properties on release kinetics.

Results, Conclusions, and Discussions: PEG hydrogel microspheres were successfully fabricated via aqueous two-phase separation (ATPS), through which microsphere diameter could be tuned by pre-reaction time, PEG concentration, pH, and temperature. The resulting diameters ranged from 5-40 microns. A variety of techniques, including NMR, FTIR, and UV-vis revealed copolymer poly(DMA-co-SMBA) effectively coated PEG microspheres. The DMA monomers provided a “mussel glue”-like adhesive surface, while SMBA monomers provided a super-lubricious surface. Rheological test revealed similar stiffness of hydrogel microsphere in the absence and presence of copolymer coating. The lubricious microspheres had a coefficient of friction lower than PEG only, OA synovial fluid, non-OA synovial fluid. Sustained release over 30 days of PRP was achieved from the PEG microspheres