The ultimate goal of our proposal is to genetically engineer a therapeutic human skin substitute for use in the treatment of skin lesions such as skin wounds (e.g., pathological or traumatic) and ulcers (e.g., venous and diabetic ulcers). Chronic skin ulcers are particularly problematic as they typically become infected resulting in impaired wound healing and increased complications with undesirable consequences such as amputation. Today's marketed therapeutic skin substitute products are cellular or acellular and composed of varying combinations of collagen-based or artificial matrixes supplemented with primary human keratinocytes and/or fibroblasts. These products have been designed to replace or compensate for non-functioning skin. However, none of the marketed products has been optimized to protect the wound bed from infection. Additionally, cellular skin therapies have been shown to be exquisitely sensitive to the toxic effects of commonly used antimicrobial agents. Human-derived, endogenous antimicrobial peptides, such as the defensins, have emerged as an exciting new therapeutic approach to enhance innate host defense mechanisms against invading microorganisms. This presents an opportunity for the development of innovative, genetically enhanced human skin substitute products which express antimicrobial peptides to defend the wound site from bacterial invasion while allowing keratinocyte proliferation and expediting wound closure. In the last year advances in ex vivo genetic engineering of a patented human keratinocyte cell line at Stratatech Corporation has made us uniquely positioned to generate genetically enhanced human skin substitutes for use in the burn and chronic skin wound market.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
1R42AR050349-01
Application #
6694727
Study Section
Special Emphasis Panel (ZRG1-GMA-1 (11))
Program Officer
Moshell, Alan N
Project Start
2003-08-01
Project End
2004-01-31
Budget Start
2003-08-01
Budget End
2004-01-31
Support Year
1
Fiscal Year
2003
Total Cost
$99,803
Indirect Cost
Name
Stratatech Corporation
Department
Type
DUNS #
160392168
City
Madison
State
WI
Country
United States
Zip Code
53719
Gibson, Angela L; Thomas-Virnig, Christina L; Centanni, John M et al. (2012) Nonviral human beta defensin-3 expression in a bioengineered human skin tissue: a therapeutic alternative for infected wounds. Wound Repair Regen 20:414-24
Centanni, John M; Straseski, Joely A; Wicks, April et al. (2011) StrataGraft skin substitute is well-tolerated and is not acutely immunogenic in patients with traumatic wounds: results from a prospective, randomized, controlled dose escalation trial. Ann Surg 253:672-83
Rasmussen, Cathy A; Gibson, Angela L; Schlosser, Sandy J et al. (2010) Chimeric composite skin substitutes for delivery of autologous keratinocytes to promote tissue regeneration. Ann Surg 251:368-76
Schurr, Michael J; Foster, Kevin N; Centanni, John M et al. (2009) Phase I/II clinical evaluation of StrataGraft: a consistent, pathogen-free human skin substitute. J Trauma 66:866-73; discussion 873-4
Gibson, Angela L; Schurr, Michael J; Schlosser, Sandy J et al. (2008) Comparison of therapeutic antibiotic treatments on tissue-engineered human skin substitutes. Tissue Eng Part A 14:629-38