Wound healing compositions and methods using tropoelastin and lysyl oxidase

Abstract

The present invention provides compositions and methods for promoting wound healing. The composition comprises virgin monomers of tropoelastin and lysyl oxidase. When the lysyl oxidase comes in contact with the tropoelastin, cross-linking of the tropoelastin monomers will occur to form elastin. Contacting the tropoelastin and lysyl oxidase together and applying the mixture to a wound before substantial cross-linking has occurred promotes wound healing by holding the damaged tissue together, increasing the rate of healing, and decreasing the amount of scarring.

Description

BACKGROUND OF THE INVENTION [0001] Wound healing is a complex biological process that involves many different cell types, many different cytokines, the extracellular matrix (ECM), and numerous interactions among them. Most wounds heal rapidly and efficiently within a week or two; however, the result is neither aesthetically nor functionally perfect. Wound contraction and scar formation are currently unavoidable results of wound healing. Scar tissue is less flexible than normal skin and can be cosmetically disfiguring, and wound contraction can lead to joint disablement (Lamme et al., J. Histochem. Cytochem. 44:1311, 1996). Scars lack elastin and consist of poorly reconstituted collagen matrix in dense parallel bundles rather than the mechanically efficient basket-weave meshwork of collagen in unwounded dermis (Martin, Science 276:75, 1997). Two major goals of wound-healing biology are more rapid wound healing and more perfect reconstruction of the damaged parts. Compositions and met...

AI Technical Summary

Benefits of technology

[0013] Without wishing to be bound by any particular theory, we propose that the lysyl oxidase catalyzes the oxidative deamination of the lysine residues of the tropoelastin monomers at the site of the wound. Then in a non-enzymatic step, cross-links form between the tropoelastin monomers as well as between tropoelastin monomers and other proteins of the extracellular matrix such as collagen. The cross-linked elastin at the site of injury helps to hold the injured tissue together and thereby promotes healing. The elastin is also chemotactic for fibroblasts, endothelial cells, and inflammatory cells, thereby promoting healing in another manner. Elastin at the site of injury also helps to lessen scarring since scar tissue is devoid of elastin, and elastin is an important component of uninjured skin. The cross-linked elastin also generally provides a favorable environment for the cells that participate in the healing process.

Problems solved by technology

Most wounds heal rapidly and efficiently within a week or two; however, the result is neither aesthetically nor functionally perfect.

Wound contraction and scar formation are currently unavoidable results of wound healing.

Immediately after tissue injury, blood vessel disruption leads to the extravasation of blood and concomitant platelet aggregation and blood coagulation resulting in fibrin clot formation.

Images