Matrix‐enabled gene transfer for cutaneous wound repair

Abstract

Several growth factor proteins have been evaluated as therapeutic agents for the treatment of chronic dermal wounds. Unfortunately, most have failed to produce significant improvements in wound healing, in part due to ineffective delivery and poor retention in the wound defect. It has been proposed that gene therapy might overcome the limitations of protein therapy via ongoing transcription and translation, thus prolonging the availability of the therapeutic protein. Reasoning that it would be of further benefit to ensure retention of the DNA vector as well as the therapeutic protein within the wound defect, we have evaluated matrix-enabled gene transfer for cutaneous wound repair (Gene Activated Matrix). Formulations consisting of bovine type I collagen mixed with adenoviral or plasmid gene vectors have been evaluated in 3 in vivo models. The therapeutic transgenes employed encode human platelet-derived growth factor-A or -B, proteins key to each phase of normal wound repair. Increased granulation tissue formation, vascularization, and reepithelialization have been shown compared to controls treated with collagen alone or collagen containing a reporter gene vector. Further enhancements of the tissue repair response have been achieved by combining matrix-enabled gene transfer with molecular targeting, in which the DNA vector is conjugated to a growth factor ligand (basic fibroblast growth factor). These promising results support the clinical evaluation of gene activated matrices for the treatment of chronic dermal wounds.

Matrices and scaffolds for DNA delivery in tissue engineering

“…Collagen is a natural biomaterial that can be used in several forms, including solutions, sponges, fiber, etc, gels at physiological temperatures, and is biodegradable. Collagen-based scaffolds have been employed with a range of non-viral and viral vectors, and are capable of inducing in vivo transgene expression and physiological improvements in applications such as bone regeneration [74,75], wound healing [76][77][78][79][80], muscle repair [81], and optic nerve repair [82]. The release kinetics and transfection efficiencies of DNA loaded collagen scaffolds are dependent on the vector, with polyplexes and lipoplexes having a slower release than plasmid alone [73].…”

Gene therapy in wound healing: present status and future directions

“…74 Further developments in matrix components and tissue engineering technology offer promise of a slow-release matrix, allowing for prolonged transgenic expression. 75 Growth factors are not the only target for gene therapy in wound healing, and some promising new approaches have recently been reported. Transcription (co-) factors such as cardiac ankyrin repeat protein or L-Sox5, Sox6, and Sox9 are active regulators in wound repair.…”

Review Paper: Burn Coverage Technologies: Current Concepts and Future Directions

“…Further developments in matrix components and tissue engineering technology offer promise of a slow-release matrix, allowing for prolonged transgenic expression [74]. Use of the skin as a bioreactor for simultaneous wound healing locally and systemic therapy to reduce hypermetabolism postburn is an yet unchartered territory and work in this area promises to be exciting with its clinical relevance.…”