R & D

Stratatech Corporation has been successful in obtaining non-dilutive funding from federal granting agencies for R&D. To date, the Company has been awarded in excess of $10 million in peer-reviewed SBIR, STTR and ATP grants to develop the NIKS™ cell technology.

Enhancing Antimicrobial Activity

Chronic diabetic skin ulcers exhibit poor blood flow and typically become infected resulting in impaired wound healing and amputation, a life threatening complication of diabetes. The standard of care for chronic, infected, nonhealing diabetic wounds is antibiotic treatment and synthetic dressings. Because bacterial strains typically encountered often become antibiotic resistant, especially in the chronic wound, the clinician is limited to more potent antibiotics with undesirable effects on viability and migration of cells in the diabetic skin ulcer. This, coupled with the growing concern over emerging new multi-resistant strains of bacteria, underscores the need for innovative approaches to supplement antibiotic treatment regimes used in open wound therapy. Stratatech Corporation's strategy to promote wound healing in infected diabetic skin ulcers is to develop novel human tissues possessing a range of enhanced antimicrobial, re-epithelialization, and vascularization properties. We have developed proven strategies for the generation of human tissues genetically engineered to secrete biologically active antimicrobial peptides capable of stimulating vascularization and cell migration. Advances in ex vivo genetic engineering of the NIKS™ keratinocytes at Stratatech Corporation have uniquely positioned the Company to generate genetically enhanced human tissues for use in the treatment of type 1 diabetic skin ulcers.

Enhancing Vascularization Properties

Cutaneous ulcers afflict approximately 4.5 million patients in the United States each year and it is estimated that 15% of older adults in the United States suffer from chronic, hard-to-heal skin wounds. Many of these wounds fail to heal, often resulting in severe complications including amputations and life-threatening infections. The healing of these wounds is often impaired by hypoxia, so strategies to enhance vascularization and simultaneously stimulate multiple repair processes have the potential to significantly improve the treatment and healing of chronic wounds. Stratatech Corporation is developing a portfolio of engineered skin tissue products to improve the management and healing of chronic skin wounds. While administration of individual angiogenic factors may stimulate some aspects of angiogenesis, the simultaneous expression of multiple factors is required to promote morphologically and functionally normal vessels. To coordinately express elevated levels of multiple therapeutic factors, Stratatech scientists have introduced a master regulator of wound healing responses into the NIKS™ keratinocytes using non-viral vectors. This product will ultimately lead to the development and commercialization of improved treatments to promote the healing of chronic wounds and other severe skin defects.

Cell-Based, Chronic Wound Therapy for Older Adults

An increase in proteolytic activity is associated with intrinsic cutaneous aging predisposing the elderly to tissue breakdown. Furthermore, chronic wounds inherently exhibit a highly proteolytic environment resulting in abnormal degradation of the extracellular matrix, critical soluble or matrix-associated growth factors, and their respective cellular receptors. Therefore, the proteolytic nature of aged skin not only contributes to impaired acute wound healing, but perpetuates existing chronic cutaneous wounds in older adults. Strategies to attenuate 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 specifically targeting the proteolytic nature of chronic wounds have been developed and marketed. Stratatech scientists have genetically enhanced human skin cells to constitutively express a functional, bioactive proteinase inhibitor. This cellular reagent is being developed by Stratatech scientists as ExpressGraft™_Shield a cell-based gene therapy product engineered to combat the excess proteolytic activity associated with chronic cutaneous wounds in the elderly.

Publications

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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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