Burn wound progression refers to the phenomenon of continued tissue necrosis in the zone of stasis after abatement of the initial thermal insult. A multitude of chemical and mechanical factors contribute to the local pathophysiologic process of burn wound progression. Prolonged inflammation results in an accumulation of cytotoxic cytokines and free radicals, along with neutrophil plugging of dermal venules. Increased vascular permeability and augmentations of interstitial hydrostatic pressure lead to edema with vascular congestion. Hypercoagulability with thrombosis further impairs blood flow, while oxidative stress damages endothelial cells and compromises vascular patency. A number of studies have investigated the utility of various agents in modulating these mechanisms of burn wound progression. However, as many of studies have used animal models of burn injury, often with administration of therapy preburn, obscuring the clinical applicability of the results to burn patients is of questionable benefit. An understanding of the complex, interrelated mediators of burn wound progression and their ultimate point of convergence in effecting tissue necrosis—cell apoptosis or oncosis—will allow for the future development of therapeutic interventions.

The bilayered dermal substitute Integra (Integra Life Sciences Corp., Plainsboro, NJ) was developed and has been widely used as primary coverage for excised acute burns. Our take has been slightly different, finding it most useful in the management of complex soft-tissue loss and threatened extremities as the result of tendon, joint, or bone exposure. Often tasked to fill significant volume loss, we have become adept at stacked multiple-layer applications. Creative use of this material has resulted in unexpected successes with distal limb salvage; the technique takes its place beside adjacent tissue transfer, composite flaps, and vascular pedicle flaps in our burn reconstructive practice. A prospective registry (44 patients) has been kept during the past 7 years that catalogs wounds with complex soft-tissue loss treated with Integra grafts. Many of these patients were at risk of extremity loss because of exposed tendons, joints, or bone. Integra was applied after 1:1 meshing. With profound soft-tissue defects, multiple layers of Integra were serially applied 1 to 2 weeks apart for reconstitution of soft-tissue contours. Local Integra graft infections were managed by silicone unroofing followed by topical sulfamylon liquid dressings. Wounds addressed included fourth-degree burns, necrotizing fasciitis, pit-viper envenomations, and total abdominal wall avulsion in one patient after being run over by a bus. Patients generally were free of pain from their wounds during the maturation phase of the Integra neodermis. Restoration of tissue contour was significantly better when using multiple layers for deep defects. Second and third layers of Integra were successfully applied after an abbreviated first graft maturation period of 7 days. Epithelial autografts on multilayer Integra applications frequently "ghosted"; they would auto-digest to dispersed cells followed subsequently by the reappearance of a confluent epithelial layer. Final grafted skin morphology over palmar and plantar surfaces assumed the type and fingerprint pattern of the original tissues. Infections were readily visible. Early recognition kept them to easily treated circumscribed areas, which did not jeopardize the entire wound. Lengths of stay were long (range, 2-246 days) but not significantly greater than with traditional techniques. The specific reconstructive use of Integra permitted unexpected salvage of several threatened extremities by protecting exposed tendons, bones and joints. Long-term histologic examination revealed unexpected persistence of Integra collagen. Large volume loss wounds benefited from the ability to fill voids with multilayered applications.