Date Published: April 01, 2017
Author(s): Suzanne M. Mithieux, Anthony S. Weiss.
We demonstrate a novel approach for the production of tunable quantities of elastic fibers. We also show that exogenous tropoelastin is rate-limiting for elastin synthesis regardless of the age of the dermal fibroblast donor. Additionally, we provide a strategy to further enhance synthesis by older cells through the application of conditioned media. We show that this approach delivers an elastin layer on one side of the leading dermal repair template for contact with the deep dermis in order to deliver prefabricated elastic fibers to a physiologically appropriate site during subsequent surgery. This system is attractive because it provides for the first time a viable path for sufficient, histologically detectable levels of patient elastin into full-thickness wound sites that have until now lacked this elastic underlayer.
The scars of full thickness wounds typically lack elasticity. Elastin is essential for skin elasticity and is enriched in the deep dermis.
Elastin is integral to the extracellular matrix of vertebrate tissues such as blood vessels, lungs and skin, where it provides the structural integrity and elasticity required for mechanical stretching of these tissues during normal function . Elastin’s three-dimensional architecture reflect its physical environment and biological demands: elastic vessels carry blood in the vasculature, the lung expands and contracts with each breath, and fibers in the dermis facilitate skin stretching and recoil. In the dermis, elastin is arrayed in the form of fibers, the dominant component of which is the elastin polymer. Although elastin is one of the most durable human proteins lasting as long as the human host ,  dogma states that elastic fiber synthesis in tissues including the dermis effectively ceases in early childhood . After this, the regeneration of elastic fibers in full thickness wounds is severely compromised . There is a strong demand for de novo elastic fiber synthesis, particularly in the deep dermis, in order to maintain viable elasticity and skin function. Elastin is mainly present in the reticular portion of the dermis where large diameter elastic fibers sit deep within the tissue and are parallel to the skin surface .
We describe a process and hybrid biomaterial intended to deliver tunable levels of histologically detectable patient elastin into full-thickness wound sites. This approach addresses a persistent unmet need because repairing wounds lack this elastic substratum. Previously, dogma asserted that elastin synthesis is attenuated in early childhood but we show here that we can overcome this restriction by adding exogenous tropoelastin, regardless of the age of the dermal fibroblast donor. We describe how to further enhance synthesis by older cells by using CM. This approach delivers elastin as a layer on the leading dermal repair template for contact with the deep dermis in order to deliver prefabricated elastic fibers to the physiologically appropriate site during surgery to repair scar tissue at sites of healing full thickness wounds.
We acknowledge funding from the Australian Research Council, National Health and Medical Research Council and Wellcome Trust.
ASW is the Scientific Founder of Elastagen Pty Ltd.