Biomimetic Coating

AVI’s Biomimetic Coating was designed by polymer scientists at the University of Utah and clinical immunologists at Uppsala University.  The surface coating is inspired by the body's natural healing mechanisms and the immune system's ability to recognize "self" from "non-self". The design incorporates elements that prevent the inflammatory processes that lead to restenosis, while still providing a favorable surface for healing and regeneration of the endothelium. AVI’s coronary stent coating has two parts. One part is a proprietary End Group Activated Polymer (EGAP). The EGAP surface technology transforms traditional device materials into biocompatible and thromboresistant surfaces and further enables the attachment of biologically active or therapeutic compounds. The second part of the coating is a protein called factor H, which interrupts the inflammatory processes that lead to restenosis.

Restenosis

Factors that lead to restenosis are introduced at the time of stent implantation when the endothelial lining and smooth muscle cells (SMC) in the artery wall are damaged. This insult and the presence of the metal stent trigger thrombus formation and complement activation, both of which cause activation of inflammatory cells. Activated inflammatory cells fuel the restenosis process by migrating into the artery wall and secreting mitogens. These in turn stimulate SMC growth and matrix production, which are the primary contributors to narrowing of the arterial lumen. Unlike restenosis after stent implantation, restenosis post angioplasty is due largely to elastic recoil with only a small contribution from neointima proliferation. Differences in the characteristics of restenosis after angioplasty and stent implantation at the molecular, cellular and macroscopic levels suggest that a foreign body response is a major contributor to the neointima formation after stenting and implicate complement activation as a cause of prolonged inflammatory stimulation.

EGAP Polymer

EGAP is a triblock copolymer that self assembles on surfaces and forms a thick brush-like layer of polyethylene oxide that acts as a protective shield to prevent protein adsorption, platelet activation, and thrombus formation. Based on proprietary end group activation chemistry, EGAP acts as a linker for binding factor H to the stent surface and allows for a high level of control over the amount of protein loaded onto the stent.

The EGAP layer, AVI's underlying proprietary coating, consists of a layer of triblock copolymer that has been modified to permit the coupling and attachment of biomolecules. After preparation of the metal stent surface, the EGAP self-assembles to form a strong bond with the material leaving end blocks freely mobile.

Using this approach, EGAP forms a thick brush-like layer at the material surface that serves two important purposes.

• By constituting a steric barrier, it prevents protein adsorption and bacterial adhesion.

• By acting as a cushion between the proteins and the substrate, it prevents any denaturing of the protein that might otherwise result from surface attachment.

Following the assembly of EGAP on the stent, in a subsequent step, specific proteins such as Factor H can be attached to the free waving arms of the modified PEO chains.The attached proteins retain their full viability as well as their "natural" orientation that allows them to interact from the surface to direct cell behavior, promote cell type selective adhesion and activate or inhibit biological signaling events.

AVI's biomimetic surface technology based on the EGAP system provides a simple and versatile solution. It can be applied to devices or device components by a simple dip coating process that renders a uniform monolayer of EGAP and protein.

Factor H

Factor H is an important protein that regulates complement activation. This regulation occurs by multiple mechanisms which include disruption of C3 convertase formation and acceleration of its decay. Factor H also acts as a cofactor to factor I in the degradation of C3b, and competes with factor B for binding to C3b. Factor H can be produced recombinantly or isolated from human plasma by conventional fractionation techniques. With AVI’s proprietary coating technology, factor H is covalently linked to stents through the activated end groups of the EGAP coating.

Covalently bound to the EGAP coating, the second layer in AVI's biomimetic surface technology for stents consists of Factor H. Factor H is a human plasma protein that controls inflammation at a very early stage while it provides a stent environment that supports healing.

Factor H is one of the principal regulators of the complement system that plays a vital role in the human immune response. Its regular functions include…

• controlling proteins that generate pro-inflammatory anaphylatoxins

• maintaining tissue integrity by identifying "self" from "non-self", and

• harnessing direct anti-inflammatory properties.

Factor H is an ideal therapeutic agent for stent coatings based on the following factors:

• the clear link between complement-triggered inflammation and restenosis,

• the regulatory role of Factor H in stopping complement-triggered inflammation and tissue damage,

• the vascular damage caused by defective Factor H in diseases such as familial Hemolytic Uremic Syndrome serving as a powerful example of pathology.

Advantages of AVI’s Biomimetic Coating

The following schematic shows how AVI’s coating is different from current drug eluting stents (DES). DES target the outcome of inflammation by preventing cell growth and migration. Cell growth and migration are important processes that are required for healing of the endothelium. A major advantage of AVI’s Biomimetic coating is that it targets inflammation at an early stage, which does not impair healing.

Mechanism of Restenosis

Summary of Advantages of AVI’s Coating:

• Prevents restenosis while supporting healing 

• Polymer component is biocompatible and thromboresistant

• Very thin coating does not alter stent profile

• Coating is securely bound to stent and does not crack, peel or form webs that may interfere with side branch flow with stent expansion

• Aqueous based coating process is environmentally friendly

• May eliminate need for longer term dual anti-platelet therapy