Fibronectin matrix mimetics are novel extracellular matrix-based biologics for promoting chronic-wound healing. Fibronectin matrix mimetics are easy to produce, elicit specific cellular responses, are stable under physiologic conditions, and combine cell binding and bioactive signals into one therapy.
Problem Solved by the Technology
Using fibronectin matrix analogs to promote the healing of chronic wounds represents a major shift in wound healing therapies. Current standard therapies rely on passive approaches that facilitate the body’s own healing response. Small molecules approved for treating ulcers improve healing through secondary mechanisms such as improving blood flow to the wound site. Biologics approved as chronic wound therapies rely on full-length proteins to exert their beneficial effects. Often times, however, full length proteins exert potent and indiscriminate signals to the wound site and beyond and can produce serious negative side-effects.
Fibronectin matrix analogs are engineered extracellular matrix-based protein peptides that can be tailored to induce multiple effects while maintaining specificity and control over the delivered signals. Fibronectin matrix analogs are small peptides engineered to contain two coupled moieties from full length fibronectin that control cellular attachment and critical cell functions such as proliferation, migration, contractility, and extracellular matrix deposition. Unlike full-length protein, fibronectin matrix analogs have the active signaling motif exposed and do not require any further cellular or physiological processing in situ. Furthermore, fibronectin matrix mimetics can be used to promote extracellular matrix deposition and, therefore, address an established barrier to proper healing of chronic wounds. This design represents an active treatment approach that can “jump-start” the body’s healing response by delivering targeted and specific signals to the wound site.
Fibronectin matrix mimetics are wound biologics that can be delivered to the wound site as additives within standard wound care formulations such as dressings, creams, or hydrogels. The technology consists of a series of distinct recombinant fibronectin peptides that can be designed to include portions of fibronectin’s bioactive heparin binding domain directly coupled to portions of fibronectin’s cell binding domain. Depending on the specific composition of the mimetic, they can be used increase cell proliferation, migration, and contractility, specify cell attachment, and modulate extracellular matrix composition. The range of cellular behaviors that can be controlled with mimetics means they can be tailored for specific wound healing applications. Addition of fibronectin matrix mimetics to wound matrices will enhance the cellular and mechanical properties of dermal substitutes for use with deep wounds and large surface burns. Moreover, the ability to promote proper extracellular matrix organization may also reduce contractures and hypertrophic scars that can develop at these sites.
For wound healing applications, fibronectin matrix mimetics’ major advantage is the ability to augment and recreate fibronectin function. Lack of fibronectin is associated with impaired healing in chronic wounds. Recombinant fibronectin mimetics have several advantages over full length extracellular matrix proteins or growth factors. First, recombinant mimetics are present in an active signaling form and do not require any physiologic modifications in situ. Second, as small molecules, mimetics are stable and are more likely to reach deeper into the wound while remaining stable. Third, fibronectin matrix mimetics have fewer binding sites for interactions with other molecules, including proteases. Finally, the mimetics are not derived from human blood products thereby circumventing host-rejection, and as recombinant proteins, are far easier and less expensive to produce.
URV Reference Number: 2-11149-11006