Porcine Wound Healing in Full-Thickness Skin Defects Using Integra™ with and Without Fibrin Glue with Keratinocytes

Abstract

An artificial dermal matrix such as Integra (Integra Life Sciences Corporation, USA) provides a wound bed template for vascular and fibrocyte ingrowth as well as collagen remodelling. Dermal repair leads to epidermal and basement membrane regeneration. Burn wounds in particular have been shown to benefit from Integra by enhanced wound healing. To evaluate the effect of fibrin glue to modify the integration of Integra in large excised cutaneous wounds. It was hypothesized that applying fibrin glue on a wound bed would reduce the time needed for matrix vascularization and incorporation of Integra and take of the cultured keratinocytes. Four separate full-thickness wounds were created on the dorsum of two swine. Wound beds were randomly assigned to either application of fibrin glue or no application of fibrin glue before application of Integra. Full-thickness biopsies were performed at days 7, 14, 21, 29 and 35. On day 21, keratinocytes were applied either as sheets or aerosolized fibrin glue suspension. Histological analysis revealed a wave of inflammatory cells and early granulation tissue ingrowth into the Integra from the fascia below on day 7. Only this initial phase was augmented by application of fibrin glue to the wound bed. By day 14, most and by day 21, all of the Integra thickness was incorporated. Accelerated dermal repair proceeded from the base with new collagen deposition in Integra spaces. There was no evidence of keratinocyte engraftment, although re-epithelialization occurred at wound edges extending onto the incorporated Integra. It appears there is an acceleration of early phase (day 7 to day 21) dermal incorporation with fibrin glue application to the wound bed, perhaps secondary to increased cellular migration. Day 21 appears to be too early to apply cultured keratinocytes either as sheets or aerosolized suspension.