DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Biologically Active Advanced Antimicrobial Human Skin Substitute for the Treatment of Combat Wounds

Principal Investigator: ALLEN-HOFFMANN, B. L
Institution Receiving Award: STRATATECH CORPORATION
Program: DMRDP
Proposal Number: DM110295
Award Number: W81XWH-12-2-0110
Funding Mechanism: Military Infectious Diseases Applied Research Award
Partnering Awards:
Award Amount: $1,565,343.00


PUBLIC ABSTRACT

Combat-related trauma and blast injuries are frequently heavily contaminated with foreign material and often become infected with multiple pathogenic microorganisms. Wound infection is a leading cause of mortality and is of particular concern during active military operations, where surgical treatments may be delayed. The increasing incidence of bacterial resistance to multiple different antibiotics represents a significant challenge to the clinical management of infected combat-related wounds and highlights the critical need to develop novel technologies to combat infection by multidrug-resistant wound pathogens. Therefore, new and innovative strategies are needed to combat bacterial colonization and infection by drug-resistant pathogens in burn, trauma, and peri-operative wounds.

In order to address the problem of antibiotic-resistant microbial infection, Stratatech Corporation has developed a novel, genetically modified skin substitute tissue that expresses sustained levels of a human antimicrobial factor. Currently available skin substitutes are contraindicated for use on infected wounds. The antimicrobial skin substitute tissue evaluated under this proposal utilizes NIKS cells, which are a unique source of genetically uniform, non-tumorigenic, pathogen-free human keratinocyte progenitors. Because they are readily amenable to genetic modification with non-viral vectors, NIKS keratinocytes are ideal for creation of human biological skin substitutes with enhanced antimicrobial capabilities. We have strategically focused on an endogenous human host defense peptide because it exhibits antimicrobial activity against a broad range of microorganisms, fungi, and viruses and is a critical component of innate defenses against wound infection. This genetically modified human antimicrobial skin substitute is a living combination skin substitute with a fully stratified epidermal layer that imparts barrier function comparable to that of native skin. In this application, we propose to complete preclinical animal efficacy studies, which are required for submission of an Investigational New Drug application to the Food and Drug Administration. The experiments proposed in this application will examine the antimicrobial tissue's ability to mitigate bacterial bioburden in infected rodent and porcine full-thickness wounds. Furthermore, testing in rodents and pigs will be conducted to ensure that the antimicrobial tissue will not cause any toxicity when grafted onto an injury. We expect that the antimicrobial tissue will represent a safe, effective, and readily available alternative to current therapies for the management of severe combat-related burn and trauma wounds. Completion of these studies will support human clinical trials utilizing the antimicrobial tissue to reduce infection and promote healing of severe trauma and burn wounds. The significant advantages offered by this technology should enhance the treatment and subsequent recovery of military personnel who incur combat-related skin wounds.