Research & Development

ExpressGraft™_Enhance: Enhancing Antimicrobial Activity

Antibiotic resistance is a growing health care concern that has a particularly profound affect on the treatment of burns and other severe skin injuries. Skin grafts are routinely used to treat such injuries, however infection is the number one cause of skin graft rejection. Also, chronic diabetic skin ulcers are especially susceptible to infection. These infections further impair wound healing and increase the risk of amputation, a life-threatening complication of diabetes. The standard of care for chronic, infected, non-healing diabetic wounds is antibiotic treatment and synthetic dressings. Because of the increasing threat of antibiotic resistance, especially in the chronic wound, the clinician is limited to more potent antibiotics with undesirable effects on cell viability and migration. There is an urgent need for innovative approaches to supplement antibiotic treatment regimes used in open wound therapy.

Stratatech’s ExpressGraft™_Enhance pipeline product has been genetically engineered to overproduce naturally-occurring antimicrobial proteins called host defense peptides. Data recently published in the journal Molecular Therapy showed there are 139-fold more anti-infective proteins in ExpressGraft™_Enhance tissue in vitro than in unmodified tissue. ExpressGraft™_Enhance tissue reduced the growth of A. baumannii, a pathogenic, multi-drug-resistant bacterium, by 100-fold in vivo compared to unmodified tissue.

ExpressGraft™ _Vascular: Enhancing Vascularization Properties

Cutaneous ulcers afflict approximately 4.5 million patients in the United States each year. It is estimated that 15% of older adults in the United States suffer from chronic, hard-to-heal skin wounds. Many of these wounds result in severe complications including amputations and life-threatening infections. Healing is often impaired by hypoxia, or oxygen deprivation, so strategies to enhance the formation of blood vessels and simultaneously stimulate multiple repair processes have the potential to significantly improve the treatment and healing of chronic wounds. To coordinately express elevated levels of multiple therapeutic factors that will promote the formation of normal vessels, Stratatech scientists have introduced a master regulator of wound-healing responses into the NIKS® keratinocytes using non-viral vectors This regulator not only causes the expression of blood-vessel-forming factors, it stimulates the production of a host of other important would-healing factors as well.

ExpressGraft™_Shield: Cell-Based, Chronic Wound Therapy for Older Adults

An increase in proteolytic activity, or activity that breaks down important proteins, is associated with aging of the skin, predisposing the elderly to tissue damage. Furthermore, chronic wounds inherently exhibit a highly proteolytic environment, resulting in abnormal degradation of important structures within the skin and the proteins that promote their growth. Therefore, the proteolytic nature of aged skin not only contributes to impaired acute wound healing, but perpetuates existing chronic skin-related wounds in older adults. Strategies to mitigate the highly proteolytic environment of chronic wounds have the potential to dramatically enhance the healing of these hard-to-heal wounds. To date, no biological treatment options targeting the proteolytic nature of chronic wounds have been developed and marketed. Stratatech scientists have genetically enhanced human skin cells to express a functional, bioactive proteinase inhibitor. These cells are the foundation of Stratatech’s ExpressGraft™_Shield, a cell-based gene therapy product that combats the excess proteolytic activity associated with chronic cutaneous wounds in the elderly.

Publications

Straseski JA, Gibson AL, Thomas-Virnig CL, Allen-Hoffmann BL. (2009) Oxygen deprivation inhibits basal keratinocyte proliferation in a model of human skin and induces regio-specific changes in the distribution of epidermal adherens junction proteins, aquaporin-3, and glycogen. Wound Repair Regen. 17(4):606-16.
View PDF

Schurr MJ, Foster KN, Centanni JM, Comer AR, Wicks A, Gibson AL, Thomas-Virnig CL, Schlosser SJ, Faucher LD, Lokuta MA, Allen-Hoffmann BL. (2009) Phase I/II clinical evaluation of StrataGraft: a consistent, pathogen-free human skin substitute. J. Trauma 66(3):866-73; discussion 873-4.
View PDF

Steinstraesser L, Al-Benna S, Kesting M, Jacobsen F. (2009) Bioengineered human skin: working the bugs out. Molecular Therapy 17(3):405-8.
View PDF

Thomas-Virnig CL, Centanni JM, Johnston CE, He LK, Schlosser SJ, Van Winkle KF, Chen R, Gibson AL, Szilagyi A, Li L, Shankar R, Allen-Hoffmann BL. (2009) Inhibition of multidrug-resistant Acinetobacter baumannii by nonviral expression of hCAP-18 in a bioengineered human skin tissue. Molecular Therapy 17(3):562-9.
View PDF

Gibson AL, Schurr MJ, Schlosser SJ, Comer AR, Allen-Hoffmann BL.(2008)Comparison of Therapeutic Antibiotic Treatments on Tissue-Engineered Human Skin Substitutes. Tissue Engineering. [Epub ahead of print] PMID: 18439105
View PDF

Slavik, MA, Allen-Hoffmann, BL, Liu, BY, Alexander, CM (2006) Wnt signaling induces differentiation of progenitor cells in organotypic keratinocyte cultures. B.M.C. Biology
View PDF

Ji L, Allen-Hoffmann BL, de Pablo JJ, Palecek SP. (2006) Generation and differentiation of human embryonic stem cell-derived keratinocyte precursors. Tissue Engineering 12(4):665-679.
View PDF

Loertscher JA, Lin T, Peterson RE, Allen-Hoffmann BL. (2002) In utero exposure to 2,3,7,8- tetrachlorodibenzo-p-dioxin causes accelerated terminal differentiation in fetal mouse skin. Toxicol. Sci. 68(2):465-472.
View PDF

Loertscher JA, Sadek CS, Allen-Hoffmann BL. (2001) Treatment of normal human keratinocytes with 2,3,7,8-tetrachlorodibenzo-p-dioxin causes a reduction in cell number, but no increase in apoptosis. Toxicol. Appl. Pharmacol. 175(2):114-120.
View PDF

Loertscher JA, Sattler CA, Allen-Hoffmann BL. (2001) 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters the differentiation pattern of human keratinocytes in organotypic culture. Toxicol. Appl. Pharmacol. 175(2):121-129.
View PDF

Allen-Hoffmann BL, Schlosser SJ, Ivarie CA, Sattler CA, Meisner LF, O'Connor SL. (2000) Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS. J. Invest. Dermatol. 114(3):444-455.
View PDF

Flores ER, Allen-Hoffmann BL, Lee D, Lambert PF. (2000) The human papillomavirus type 16 E7 oncogene is required for the productive stage of the viral life cycle. J. Virol. 74(14):6622-6631.
View PDF

Flores ER, Allen-Hoffmann BL, Lee D, Sattler CA, Lambert PF. (1999) Establishment of the human papillomavirus type 16 (HPV-16) life cycle in an immortalized human foreskin keratinocyte cell line. Virology 262(2):344-354.
View PDF