Synthesis and characterization of a lubricin mimic (mLub) to reduce friction on the articular cartilage surface

Lawrence, Alexandra M. M.S.B.M.E., Purdue University, May 2015. Synthesis and Characterization of a Lubricin Mimic (mLub) to Reduce Friction of the Articular Cartilage Surface. Major Professors: Alyssa Panitch and Corey Neu. The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; downregulation of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that resists enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a mucin-like chondroitin sulfate backbone with collagen II and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated collagen II and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction to control levels as assessed over macroto micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction, ideal to help suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for viscosupplementation treatment in early osteoarthritis following injury.