SBIR-STTR Award

Each year, 70,000 patients in the United States need to have their diseased heart valves replaced with artificial devices. Although bioprosthetic valves have few complications and are considered ideal for most patients, they wear out in 12-15 years. Because surgery to replace a worn out valve carries significant operative mortality, bioprostheses cannot be implanted into patients younger than 65. We have addressed the durability problems of bioprosthetic valves, and the associated risk of reoperation, by developing a rapidly exchangeable bioprosthetic valve that can be replaced without conventional open-heart surgery. The novelty of this approach is a two-component valve, consisting of a permanent "docking station" that remains affixed to the patient's aorta, and a collapsible frame that supports the leaflets and plugs into the docking station. Once the original leaflets wear out, they can be quickly exchanged with a new set using minimally invasive surgery. The specific aims of this Phase I research proposal focus on identifying and testing non-adhesive coatings to prevent tissue overgrowth in the area where the two components mate together and disengage. We aim to (J) identify a number of coatings that can be applied to metals and plastics to render them non-thrombogenic and non-adhesive to cellular overgrowth, (ii) develop, manufacture and coat test fixtures that can be implanted into a sheep model to investigate tissue overgrowth, and (iii) explant the test fixtures after 3 months and measure the thickness of pannus and its impact on the forces required to disengage and re-engage the mating components. This study builds upon our previous SBIR project in which functional prototypes of the two-piece valve were tested in vitro and in vivo. We will continue to work with the Cleveland Advanced Manufacturing Center and the University of Wisconsin. Through these proposed studies, we will demonstrate that anti-adhesion coatings can be applied to our two-piece valve to prevent pannus overgrowth in the areas where the two components connect. Once we have achieved these objectives, we will apply for Phase II funding

Each year, over 100,000 patients in the United States need to have their diseased heart valves replaced with artificial devices. Although bioprostheses, valves made from animal tissues, are considered ideal for most patients, they wear out in about 15 years. They are thus used primarily in the elderly patient who is not expected to outlive the valve. Younger patients receive mechanical valves that are more durable, but require chronic administration of blood thinners. This makes participation in most sports impossible and exposes the patient to increased risk for fatal bleeds and strokes. ValveXchange, Inc. ( VXI ) is a medical device company developing a two-part heart valve consisting of a surgically implanted base and an exchangeable bioprosthetic tissue leaflet set. The VXI device is a lifetime tissue valve replacement system that does not require anticoagulation. During the first surgery, the docking station is first sewn in place and the leaflets are snapped in. This allows the surgeon to place sutures more conveniently, without risk of damaging the leaflet core. As the leaflet set begins to show signs of wear it can be exchanged rapidly, using a minimally invasive surgical or percutaneous procedure. Rapid, minimally invasive leaflet exchange dramatically reduces surgical time and eliminates the need the technically demanding and potentially dangerous re-excision of the initial prosthetic valve. As the leaflet set is exchanged, the docking station remains permanently in place so there is no disruption of the sensitive tissue of the aortic root; a vital part of the conduction system of the heart and the origin of the coronary arteries. VXI has successfully completed two Phase I projects. In the first, VXI developed prototype exchangeable valves and demonstrated their technical feasibility in an animal model by exchanging a valve in 23 seconds. In the second, VXI investigated the ability of anti-adhesion coatings to abate fibrotic overgrowth in the hyper-fibrotic sheep model. In this Phase II application we propose to implement our novel anti-adhesion coatings in a chronic sheep model and investigate the long-term host response of the rapidly exchangeable valve. We will fabricate 8 valves each from bare cobalt-chrome, cobalt-chrome treated with a stearate coating, and from pyrolitic carbon. Both stearate and pyrolitic carbon have been shown to repel fibrotic overgrowth in the Phase I study. A control group will make use of the gold standard Edwards pericardial valve. After 3 and 5 months of implantation, the leaflet sets will be exchanged using an open surgical procedure in which the reduced time on cardiac bypass will be documented, and the degree of fibrotic overgrowth measured. Detailed measurements of fibrotic overgrowth and incidence of thromboembolism will be examined at necropsy. This revised resubmission now includes more specific criteria upon which to base a redesign of the valve and the anti-fibrotic coatings. Each year, over 100,000 patients in the United States need to have their diseased heart valves replaced with artificial devices. Although artificial heart valves made from materials of animal origin are considered ideal for most patients, they wear out in about 15 years. They are thus used primarily in the elderly patient who is not expected to outlive the valve. Younger patients receive mechanical valves, made from metals and graphite-like materials. Although these types of valves will last the life of the patient, they require the patient to be on blood thinners. This makes participation in most sports impossible and exposes the patient to increased risk for fatal bleeds and strokes. ValveXchange, Inc. ( VXI ) is a medical device company developing a two-part heart valve consisting of a surgically implanted base and an exchangeable animal tissue-based leaflet set. The VXI device is a lifetime tissue valve replacement system that does not require the patient to be on blood thinners. During the first surgery, the docking station is first sewn in place and the leaflets are snapped in. This allows the surgeon to place his stitches more conveniently, without risk of damaging the leaflet core. As the leaflet set begins to show signs of wear it can be exchanged rapidly, using a minimally invasive surgical or catheter-based procedure. Rapid, minimally invasive leaflet exchange dramatically reduces surgical time and eliminates the need the technically demanding and potentially dangerous re-excision of the initial valve. As the leaflet set is exchanged, the docking station remains permanently in place, so there is no disruption of the sensitive tissue of the aortic root a vital part of the conduction system of the heart and the origin of the coronary arteries. VXI has successfully completed two Phase I projects. In the first, VXI developed prototype exchangeable valves and demonstrated their technical feasibility in an animal model by exchanging a valve in 23 seconds. In the second, VXI investigated the ability of anti-adhesion coatings to abate tissue overgrowth in the sheep, an animal known to generate a prolific healing response. In this Phase II application we propose to implement our novel anti-adhesion coatings in the sheep model and investigate the long-term response of the host to the rapidly exchangeable valve. We will fabricate 24 valves with the mating surfaces between the docking station and the leaflet set made from biocompatible materials, such as steel treated with a number of anti-adhesion coatings shown to repel tissue overgrowth in the Phase I study. A control group consisting of a commercially available valve from a well-established manufacturer will also be used. After 3 and 5 months of implantation, the leaflet sets will be exchanged using an open surgical procedure in which the reduced time on cardiac bypass will be documented, and the degree of tissue overgrowth measured. Detailed measurements of fibrotic overgrowth and incidence of thromboembolism will be examined at necropsy. This revised resubmission adds additional criteria on which redesign of the valve and the anti-adhesion coatings may be necessary.

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