Matrix-Enabled Gene Delivery for Ischemic Tissue Repair

Transverse rectus abdominus musculocutaneous (TRAM) flaps are commonly used for tissue reconstruction, especially as required following mastectomy. The success of these flaps is highly dependent on maintaining an adequate blood supply. Despite surgical advances, there remains a relatively high rate of flap necrosis. We propose to improve the survival rate of TRAM flaps through the use of matrix- enabled delivery of growth factor genes. Specific Aim #1 will expand on preliminary data to compare platelet-derived growth factor-B (PDGF-B) and fibroblast growth factor genes for their ability to promote tissue survival in a rat TRAM flap model. Quantitative measures of tissue survival, vascularity and endogenous gene expression will be performed to demonstrate efficacy. Specific Aim #2 will use the most effective of these genes to identify the optimal delivery schedule. Specific Aim #3 will evaluate the ability of cationic liposomes and peptides to increase the potency of DNA transfection. The data generated will establish the groundwork required for the future application of this therapeutic approach in Phase II studies and ultimately in human clinical trials. PROPOSED COMMERCIAL APPLICATIONS: Pedicled TRAM flaps have become increasingly popular for tissue reconstruction, especially as required following mastectomy. TRAM flaps are appealing because they eliminate implant procedures and their associated risks. There is a significant incidence of tissue necrosis associated with TRAM flap procedures, and therefore improvements to the procedure are needed. The proposed studies evaluate a non-surgical approach, to be employed in advance of TRAM surgery that may lead to increased rates of TRAM flap survival. This approach could be applied to a variety of tissue reconstruction procedures.