Mammals use natural lubricants, known as synovial fluid to keep their joints moving smoothly. With age, arthritis and other ailments, these fluids are frequently not present in sufficient quantities. In these cases the synovial fluid, which contains a high molecular weight polysaccharide known as hyaluronic acid, can be replaced by naturally occurring fluids from other organisms or chemically crosslinked hyaluronic acid (Synvisc). These replacement fluids, however, are susceptible to enzymatic degradation leading to the need for repeated treatments. Grinstaff and coworkers recently published an article in the Journal of the American Chemical Society about using ring-opening metathesis polymerization (ROMP) to synthesize synthetic joint lubricants. By mimicking the physical properties of the fluid rather than the chemical structure, the new ROMP-based synthetic “synovial fluid” can perform the desired joint lubrication function with decreased risk of enzymatic attack. The mechanical properties of bio-polymers are notoriously complex but Grinstaff and workers seem to have done an excellent job of separating out the key attributes of coefficient of friction, storage and loss moduli and optimizing them based on molecular weight which is readily controlled using ROMP.
ROMP of the readily available oxanorbornene carboxylic acid methyl ester monomer followed by hydrolysis provides high molecular weight polymers with the key carboxylate moiety necessary for the lubricating qualities expected in the presence of saline. Achieving a high molecular weight polymer was critical for this application in order to increase the residence time in the joint. By adjusting the monomer to catalyst ratio in the ROMP, Grinstaff and coworkers were able to achieve lubricants with molecular weights ranging from 2.5 MDa to 3.7 MDa. The coefficient of friction was evaluated in ex vivo experiments and compared with bovine synovial fluid (BSF) and Synvisc. The 2.5 MDa ROMP polymer had an equivalent coefficient of friction to the BSF and a lower coefficient of friction than Synvisc. Rheology studies indicated that the polymers have excellent properties for dissipating energy on load bearing surfaces. The loss and storage moduli were somewhat different from natural synovial fluids but were closer to the target than Synvisc whose crosslinking leads to a significantly higher viscosity. Finally, the ROMP polymers were not cytotoxic and were not degraded by the enzyme hyaluronidase.
As someone who has spent time studying ROMP-based biopolymers (and as someone who likes to go jogging), I am always excited to see a paper that further demonstrates that many polynorbornenes and/or polyoxonorbornenes are not cytotoxic. The medical community is often cautious about new materials and as more examples appear in the literature with in vitro or even in vivo uses of ROMP polymers, their comfort level will increase and enable greater possibilities for the use of ROMP for medical devices and tissue engineering.
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