Synovial Fluid Lubricant Properties Are Transiently Deficient After Arthroscopic Articular Cartilage Defect Repair With Platelet-Enriched Fibrin Alone and With Mesenchymal Stem Cells

Abstract

Background Following various types of naturally-occurring traumatic injury to an articular joint, the lubricating ability of synovial fluid is impaired, with a correlated alteration in the concentration and/or structure of lubricant molecules, hyaluronan and proteoglycan-4. However, the effect of arthroscopic cartilage repair surgery on synovial fluid lubricant function and composition is unknown. Hypothesis Arthroscopic treatment of full-thickness chondral defects in horses with (1) platelet-enriched fibrin or (2) platelet-enriched fibrin+mesenchymal stem cells leads to equine synovial fluid with impaired lubricant function and hyaluronan and proteoglycan-4 composition. Study Design Controlled Laboratory Study. Methods Equine synovial fluid was aspirated from normal joints at a pre-injury state (0 days) and at 10 days and 3 months following fibrin or fibrin+mesenchymal stem cell repair of full thickness chondral defects. Equine synovial fluid samples were analyzed for friction-lowering boundary lubrication of normal articular cartilage (static and kinetic friction coefficients) and concentrations of hyaluronan and proteoglycan-4, as well as molecular weight distribution of hyaluronan. Experimental groups deficient in lubrication function were also tested for the ability of exogenous high-molecular weight hyaluronan to restore lubrication function. Results Lubrication and biochemical data varied with time after surgery but generally not between repair groups. Relative to pre-injury, kinetic friction was higher (+94%) at 10 days but returned to baseline levels at 3 months while static friction was not altered. Correspondingly, hyaluronan concentration was transiently lower (-64%) and shifted towards lower molecular weight forms, while proteoglycan-4 concentration was increased (+210%) in 10-day samples relative to pre-injury levels. Regression analysis revealed that kinetic friction decreased with increasing total and high molecular weight hyaluronan. Addition of high molecular weight hyaluronan to bring 10-day hyaluronan levels to 2.0mg/ml restored kinetic friction to pre-injury levels. Conclusion Following arthroscopic surgery for cartilage defect repair, synovial fluid lubrication function is transiently impaired, in association with decreased hyaluronan concentration. This functional deficiency in synovial fluid lubrication can be counteracted in vitro by addition of high molecular weight hyaluronan. Clinical Relevance Synovial fluid lubrication is deficient shortly following arthroscopic cartilage repair surgery, and supplementation with high molecular weight hyaluronan may be beneficial.

Synovial fluid lubricin increases in spontaneous canine cruciate ligament rupture

“…As compared to rodent and rabbit models, synovial fluid acquisition is more reliable in large animal models such as the dog, sheep, and horse, where synovial fluid can be directly aspirated without the requirement for joint lavage. Interestingly, elevated synovial fluid lubricin has been observed in both experimental and naturally occurring PTOA in horses [19][20][21][22]39 , similar to that observed in spontaneous canine RCCL in the current study.…”

“…However, elevated synovial fluid lubricin concentrations have been reported in humans with tibial plateau fracture and late-stage OA 17,18 . Similar increases in synovial fluid lubricin have also been observed in several studies in both experimentally-induced and naturally occurring PTOA models in horses [19][20][21][22] . However, studies evaluating synovial fluid lubricin in other large animal models, especially large animal models of knee joint instability, are lacking.…”

Hyaluronan concentration and size distribution in human knee synovial fluid: variations with age and cartilage degeneration

“…The concentration of HA within each M r range was calculated as the proportion of HA in that range multiplied by the overall HA concentration. Since the molecular weight distribution of HA in SF is typically graded [ 23 ], the exact choice of HA M r bins would not be expected to affect the main results, and we chose the bins used in our previous studies [ 3 , 25 ].…”

The Challenge and the Promise of Bone Marrow Cells for Human Cartilage Repair

“…Synovial fluids from animal and human subjects with injured and diseased joints show elevated levels of inflammatory mediators and catabolic factors as well as reduced lubrication and fragmentation of hyaluronic acid compared with healthy controls. 40,41 These changes reflect altered joint biology that can adversely affect stem cell survival and cartilage repair processes. Following arthroscopic treatment of full-thickness chondral defects in horses with APEF, Grissom et al showed a transient reduction in synovial fluid lubrication.…”

“…Following arthroscopic treatment of full-thickness chondral defects in horses with APEF, Grissom et al showed a transient reduction in synovial fluid lubrication. 41 In a study of ACL-injured subjects, Cameron et al show variability between individuals with some exhibiting prolonged elevation of inflammatory mediators. 40 Work by Lewis et al showing improved intrinsic cartilage repair in superhealer mice that are able to rapidly dampen the initial inflammatory response after joint injury.…”