Chronic skin wounds are a family of diseases that afflict more than 2.5 million Americans annually, particularly the elderly. Diseases within this family include diabetic foot ulcers, venous stasis ulcers, and pressure ulcers. Chronic skin wounds severely restrict a patient's mobility, and can lead to cellulitis, osteomyelitis, sepsis and death. Despite the recent introduction of advanced therapeutic products such as recombinant platelet derived growth factor, and artificial skin products, the healing of chronic wounds is extremely slow and often times ineffective. Between 40 and 50% of patients with chronic wounds are not curable. Costs of chronic wound treatment have been estimated at $5 - 7 billion annually, with about $2.57 billion of this spent directly on treatment products. For the treatment of chronic wounds, we intend to develop a novel cell-based therapeutic patch that will supply growth factors to the wound site. The patch consists of a matrix membrane with a monolayer of amniotic cells (which evade rejection by the host immune system) that can be applied directly to the surface of the wound. The amniotic cells are genetically engineered to achieve sustained production and secretion of growth factors, for direct release into the wound site, to promote wound healing. By comparison, other growth factor-based therapies for wound healing rely on application of pre-formed growth factor, which may be rapidly destroyed due to "hyperactive proteolytic activity"- excessive protein destruction-which is an important feature of many chronic wounds. Because the genetically engineered amniotic cells supply sustained high levels of growth factors that are produced and delivered locally, the problem of protein degradation can be overcome. Proof of concept experiments, which show that sustained protein delivery can be achieved using amniotic cells, have been successfully completed. In addition, we have demonstrated the ability of this system to promote wound healing in ischemic (low blood supply) animal models with a prototype product. The purpose of this SBIR Phase I project will be to perform important experiments that are needed to guide refinements in the design of the therapeutic patch for the treatment of chronic wounds, in order to pave the way for Phase II studies. Phase II studies will involve extension of animal testing to two additional skin wound healing models: porcine and guinea pig. We believe that the use of engineered amniotic cells for delivery of growth factors to a wound site provides a significant advantage compared to other products for the treatment of chronic wounds. We believe that our product provides the only strategy for both in situ production and in situ secretion of a therapeutic molecule for wound healing. In addition, our technology allows for the production and delivery of more than one therapeutic molecule. Secretion of protease inhibitors, anti-inflammatory molecules and perhaps anti-microbial proteins, in addition to growth factors, may provide further enhancement of the wound healing process. While the technology is targeted for the treatment of chronic wounds, it may also be useful for the treatment of many skin diseases, for treatment of burns, and for treatment of eye diseases
