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 6 J 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 retropatellar cartilage in this model as a result of a 6 J 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 ofel88 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 ofjoint cartilage after P188 intervention.

Acute repair of chondrocytes in the rabbit tibiofemoral joint following blunt impact using P188 surfactant and a preliminary investigation of its long-term efficacy

“…The concentration level was established in previous studies by this laboratory. 21,24,29 The right legs of these animals received a 1.5-mL sham injection of sterile PBS into the joint. The ''4-day no P188'' animals, received sham injections of 1.5-mL sterile PBS into both the impacted left limb and the opposite, right limb.…”

“…31 The cell viability analyses followed previous procedures. 21 Briefly, slices from each compartment of the femur and tibia were rinsed with PBS and stained with calcein AM and ethidium homodimer (EthD-1), according to the manufacturer's specifications (Live/Dead Cytotoxicity Kit, Molecular Probes, Eugene, OR, USA). Prior to imaging, each sample was rinsed three times with PBS to remove excess stain.…”

“…19 This acute injury may provide a basis for the initiation of chronic joint disease. 19,20 In a previous study, our laboratory has shown that a single, 6 J of energy blunt insult to the rabbit PF joint leads to a significant increase in the percentage of acutely damaged chondrocytes, 21 as well as acute surface fissures, progressive degradation of retropatellar surface cartilage, and thickening of underlying subchondral bone 3 years posttrauma. 22 The authors of these previous studies hypothesized that the chronic cartilage degradation may be partly due to acute damage of chondrocytes.…”

“…Recent studies on brain trauma suggest that P188 can help ''save'' neurons from early necrotic death following severe mechanical loading. 27,28 Furthermore, P188 has been shown to reduce cell damage after in vivo loading of the rabbit PF joint, 21 as well as after in vitro impacts to bovine chondral 29 and osteochondral 5 explants. A previous study, using the constrained rabbit tibiofemoral (TF) joint, documents a significant increase in the percentage of acutely damaged chondrocytes following a single, 13 J of energy impact on the joint.…”

Effect of intermittent cyclic preloads on the response of articular cartilage explants to an excessive level of unconfined compression

“…6,7 Research on animal models 8 shows that acute cartilage trauma causing matrix damage and cell death can lead to chronic disease. A more recent study 9 shows that during acute trauma, contact pressure averages 25 MPa and induces acute chondrocyte necrosis.…”