Grinstaff Group - BME/Chemistry - Boston University


Synovial fluid is the clear, viscous liquid that efficiently lubricates the articular cartilage lining the ends of bones in synovial joints such as the knee and hip. Healthy synovial fluid contains the 3-7 MDa polysaccharide hyaluronic acid (HA), which affords optimal lubrication, shock absorption, and viscoelastic properties for sustained joint function over the majority of one’s lifetime. In functionally compromised joints, such as those afflicted with osteoarthritis, it is known that the concentration and molecular weight of HA have decreased. In fact, one of the current treatments for knee osteoarthritis is injection of HA or cross-linked HA to replenish the HA and thereby improve joint performance (i.e., viscosupplementation). For example, Synvisc, a currently used viscosupplement, is a 0.8 wt/vol% cross-linked HA formulation of molecular weights ranging from 5 to 7 MDa. There is significant controversy surrounding the use of intra-articular injections of HA due to its limited clinical efficacy, susceptibility to enzymatic degradation by hyaluronidase, and short residence time (t1/2 = 24 h) in the synovial joint.

Therefore, our group has developed a high-molecular-weight, hyaluronidase-resistant polysaccharide mimic. The polyanion sodium poly(7-oxanorbornene-2-carboxylate) is synthesized by ring-opening metathesis polymerization of methyl 5-oxanorbornene-2-carboxylate. When dissolved in aqueous solution and applied to the surface of human cartilage it reduces the friction at the interface and acts as a lubricant. Its performance is similar to that of synovial fluid and superior to those of saline and Synvisc in an ex vivo human cartilage plug-on-plug model. The polymer is also not readily degraded by hyaluronidase or cytotoxic to human chondrocytes in vitro. As such, this polymer is a new type of viscosupplement, and the results provide insight into the design requirements for synthesizing highly efficacious synthetic biolubricants.

Selected Publications
