The limitation of acute necrosis in retro-patellar cartilage after a severe blunt impact to the in vivo rabbit patello-femoral joint

Abstract

We have previously shown that surface lesions and acute necrosis of chondrocytes are produced by severe levels of blunt mechanical load, generating contact pressures greater than 25 MPa, on chondral and osteochondral explants. We have also found surface lesions and chronic degradation of retro-patellar cartilage within 3 years following a 6J impact intensity with an associated average pressure of 25 MPa in the rabbit patello-femoral joint. We now hypothesized that cellular necrosis is produced acutely in the retro-patellar cartilage in this model as a result of a 6J impact and that an early injection of the non-ionic surfactant, poloxamer 188 (P188), would significantly reduce the percentage of necrotic cells in the traumatized cartilage. Eighteen rabbits were equally divided into a 'time zero' group and two other groups carried out for 4 days. One '4 day' group was administered a 1.5 ml injection of P188 into the impacted joint immediately after trauma, while the other was injected with a placebo solution. Impact trauma produced surface lesions on retro-patellar cartilage in all groups. Approximately 15% of retro-patellar chondrocytes suffered acute necrosis in the 'time zero' and '4-day no poloxamer' groups. In contrast, significantly fewer cells (7%) suffered necrosis in the poloxamer group, most markedly in the superficial cartilage layer. The use of P188 surfactant early after severe trauma to articular cartilage may allow sufficient time for damaged cells to heal, which may in turn mitigate the potential for post-traumatic osteoarthritis. Additional studies are needed to improve the efficacy of this surfactant and to determine the long-term health of joint cartilage after P188 intervention.

Chronic changes in the rabbit tibial plateau following blunt trauma to the tibiofemoral joint

“…The slight, chronic loss of tissue proteoglycans documented in impacted tibial cartilage is also consistent with a study after acute, freezing death of chondrocytes (Simon et al, 1976). Another study (Rundell et al, 2005) also shows that the appearance of acute surface lesions on retropatellar cartilage in our PF joint trauma model, generating 6767134 N of impact force on the joint, damages 45% of superficial and 30% of deep zone chondrocytes. Degeneration of the articular cartilage and thickening of the underlying subchondral plate have been documented at 1 year post-trauma in that PF model (Ewers et al, 2002).…”

Pathogenesis and Prevention of Posttraumatic Osteoarthritis After Intra-articular Fracture

“…47 Administration of P188 surfactant, a cell membrane stabilizer and inhibitor of stress-related p38 mitogen-activating protein, can limit cell necrosis after impact loading of cartilage. 48 Blocking the fibronectin pathway has been shown to decrease progressive cell damage and matrix degeneration. 49 Local administration of antioxidants (eg, N-acetylcysteine, superoxide dismutase, vitamin E) within hours of traumatic injury to cartilage has been shown to prevent progressive, mechanically induced chondrocyte damage and matrix degeneration in vitro.…”

Efficacy of P188 on lapine meniscus preservation following blunt trauma

“…Immediately after impact, treated animals received a single 1.5mL injection of 8 mg/mL P188 in sterile phosphate buffered saline (PBS) into the left tibiofemoral (TF) joint (impacted treated) 3,34,38 . Right limbs of the treated animals, “non-impacted treated”, received a single 1.5 mL injection of sterile PBS.…”

“…A non-ionic surfactant, P188, has shown promise in preventing cell death in articular cartilage and neurons of the brain by inserting into cell membranes of damaged cells and restoring their integrity 19,23,31,34,38 . P188 is an 8400 Da tri-block polymer with a poly(oxyethylene) – poly(oxypropylene) – poly(oxyethylene) structure.…”