Elastatropin® in Wound Healing
Wound healing is a complex process that involves many different matrix proteins and cell types. Most wounds heal rapidly and efficiently but the results are far from perfect. Scar tissue is less flexible than normal skin and can be cosmetically disfiguring, and wound contraction can lead to disablement. Scars lack elastin and consist of a poorly reconstituted collagen matrix in dense bundles, so scar tissue is not as strong. Two major goals of tissue repair are more rapid healing and more complete reconstruction of the damage.
Wound healing has several phases including formation of a clot and "scab", recruitment of inflammatory cells, reepitheliazation, and matrix formation and remodeling. Reepithelialization of the wound site begins after several hours and is performed by the basal keratinocytes which crawl over the extracellular matrix of fibrin and fibronectin and secrete components of the Extracellular Matrix. Some time later, epidermal cells begin to reproduce. Cells of the new epidermis undergo a differentiation program of cells in the outer layers of unwounded epidermis. A new stratified epidermis is reestablished from the margins of the wound inward. New Extacellular Matrix formation begins simultaneously with reepithelialization. The matrix is continuously altered over time with the accumulation of collagen that provides the scar with tensile strength. Elastin fibers, which are responsible for the elasticity of tissue, are only detected in human scars years after the injury.
Many methods have been proposed and tested to promote wound healing and limit scarring; however, better methods and compositions are still needed. These methods include cyanoacrylate tissue adhesives, a combination of epidermal transplantation and a collagen/elastin dermal substitute, application of collagen and glycosaminoglycans to the site of injury, and biocompatible adhesives with collagen.
We are evaluating elastin compositions and methods for the promotion of wound healing. These compositions comprise virgin monomers of tropoelastin and cross-linking reagents (catalysts). The method of application is mixing these two components of the composition together (much like mixing together "tube A" and "tube B" of Epoxy adhesive) and applying them to a wound before substantial cross-linking has occurred. The tropoelastin monomers and cross linker only come in contact with each other immediately before application to the wound or during application to the wound, and cause the elastin to "gel" on the wound.
The cross-linked elastin at the site of injury helps to hold the injured tissue together and promotes healing. The elastin is also chemotactic for fibroblasts, endothelial cells, and inflammatory cells, promoting healing in another manner. Elastin at the site of injury may also help to lessen scarring since scar tissue is devoid of elastin, an important component of uninjured skin. The cross-linked elastin also provides a scaffold to support the cells that participate in the healing process. The elastin gel can also be used to carry other cells and healing-promoting matrix proteins to the site of the wound.
We make the tropoelastin monomers and purify them to homogeneity using laboratory techniques. The mixed monomer and crosslinker can be applied at the time of the injury or more than once over the course of wound healing. The tropoelastin and crosslinker may also be used in conjunction with sutures, staples, or adhesive strips in closing the wound. This approach may also be used in promoting the healing of wounds or incisions involving organs and structures with elastic fibers such as arteries, lung tissue, or skin.