IN VITRO HUMAN SKIN IRRITATION TEST FOR EVALUATION OF MEDICAL DEVICE EXTRACTS.

Purpose: The aim of this study was to determine if the EpiDerm™ reconstructed human skin model (MatTek Corp.) could be an acceptable alternative to the ISO 10993-required rabbit skin irritation test for assessing medical device biocompatibility. Eleven medical device polymers were tested. Four extracts were prepared per polymer, two each with saline and sesame oil; half were spiked with two R-38 irritants, lactic acid for saline extracts and heptanoic acid for the sesame oil extracts. Tissue viability was assessed by MTT reduction and the proinflammatory response was assessed by IL-1α release. LOAELs of 2% for lactic acid in saline and 0.7% for heptanoic acid in sesame oil were determined. A cell viability reduction of >50% was indicative of skin irritation. Cells exposed to saline extracts spiked with 3.25% lactic acid had significantly reduced mean cell viabilities (12.6–17.2%). Cells exposed to sesame oil extracts spiked with 1.25% heptanoic acid also exhibited reduced mean cell viabilities (25.5%–41.7%). All spiked cells released substantial amounts of IL-1α (253.5–387.4 pg/ml) signifying a proinflammatory response. These results indicate that the EpiDerm™ model may be a suitable in vitro replacement for the assessment of the irritation potential of medical device extracts.

Biocompatibility, EpiDerm (EPI-200), IL-1a, ISO 10993, Lowest observable adverse effect level (LOAEL), Medical device biocompatibility, medical device extracts, No observed adverse effect level (NOAEL), rabbit skin irritation test, skin irritation 

Ethylene tetrafluoroethylene, heptanoic acid, lactic acid, Liquid silicone rubber, Phthalate-free PVC, Polycarbonate, Polycarbonate–urethane, Polyether ether ketone, Polyurethane elastomer,sesame oil, Silicone polyether urethane, Silicone rubber adhesive