title: Synthesis and characterization of a lubricin mimic (mLub) to reduce friction and adhesion on the articular cartilage surface.
abstract: 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; decreased expression 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 is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen 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 type II collagen 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, and adhesion, to control levels as assessed over macro-to 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 and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lawrence
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Bible
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Calve
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Corey P
authors.initials: CP
authors.lastname: Neu
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA. Electronic address: apanitch@purdue.edu.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Panitch
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion; D011508:Chondroitin Sulfate Proteoglycans / Q000138:chemical synthesis / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry; D024043:Collagen Type II / Q000378:metabolism; D017276:Friction; D006023:Glycoproteins / Q000737:chemistry*; D006168:Guinea Pigs; D006820:Hyaluronic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008153:Lubrication; D018625:Microscopy, Atomic Force; D015233:Models, Statistical; D010003:Osteoarthritis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D010455:Peptides / Q000737:chemistry; D011509:Proteoglycans / Q000378:metabolism; D012212:Rheology; D013499:Surface Properties; D013582:Synovial Fluid; D014357:Trypsin / Q000737:chemistry; D000099158:Proteoglycan 4
chemical_list: D001672:Biocompatible Materials; D011508:Chondroitin Sulfate Proteoglycans; D003094:Collagen; D024043:Collagen Type II; D006023:Glycoproteins; D006820:Hyaluronic Acid; D010455:Peptides; D011509:Proteoglycans; D014357:Trypsin; D000099158:Proteoglycan 4; C000609883:lubricin mimic; C049816:hylan
keywords: Hyaluronan (HA); Osteoarthritis therapy; Superficial zone protein (SZP); Synvisc; Viscosupplementation