SBIR-STTR Award

Congenital heart disease affects approximately 40,000 newborns each year in the U.S. Valve repairs are needed for pulmonary valve, particularly for patients with the diagnoses of tetralogy of Fallot, tetralogy of Fallot with absent pulmonary valve, tetralogy of Fallot with AV canal, pulmonary valvar stenosis, and pulmonary valvar atresia. An additional group are patients with a prior repair of tetralogy of Fallot and pulmonary valvar regurgitation. This latter group may be the largest, and currently receive bioprosthetic valves in surgically or by catheterization. The longevity of both of these types of pulmonary valve replacements is limited. Leaflet repair materials in current use include autologus pericardium; glutaraldehyde treated bovine pericardium, and polytetrafluorethylene (PTFE). The limitations of these materials involve to varying degrees their thrombogenicity, durability, susceptibility to infection, and lack of growth potential. These materials also have varying degrees of stiffness and flexibility, which present technical challenges for surgeons, particularly in neonates and infants where size constraints and limited space in the mediastinum combine with the relatively thin immature native vascular tissues to create tissue-materials mechanical mismatches, which can compromise the ability to achieve a successful surgical repair. Current clinical experience indicates that young age, in particular, is an important risk factor for shortened intervention free survival in patients requiring these valves as part of their initial surgical repair. The goal of creating a leaflet repair patch that will overcome these limitations has not been achieved. We propose to develop a commercializable leaflet repair patch prototype and test the regenerative potential of decellularized and pentagalloyl glucose (PGG) treated porcine aortic valve leaflet repair patch with attached aortic wall (TxGuard-LP) that would repopulate with host cells and slowly regenerate and grow with the patient without unwanted inflammation and degeneration in contrast to the existing repairing procedures. Our specific aims for STTR Phase I are: Specific Aim 1: Evaluate TxGuard-LP for material properties after sterilization and extended storage such as suture pull out test, biaxial mechanical testing, and enzymatic resistance. We will also test sterility assurance level and rinsing protocols for further implantation. Specific Aim 2: Evaluate TxGuard-LP for biocompatibility. This will include 30, 60, and 90-day subdermal implantation in juvenile rats to assess calcification resistance, inflammatory cellular response and remodeling. Specific Aim 3: Evaluate TxGuard-LP for functional assessment in growing lamb as a pulmonary leaflet replacement patch for three months to assess safety, function, biocompatibility, and cellularization by the host cells in a circulatory environment.

Public Health Relevance Statement:
Congenital heart disease affects approximately 40,000 newborns each year in the U.S. Valve repairs are needed for malformed pulmonary valve, aortic stenosis (Konno procedure, Ross procedure), double outlet right ventricle (Rastelli operation), extracardiac conduit (Fontan operation), pulmonary valve replacement (Tetralogy of Fallot). Current replacement materials are suboptimal with high failure rate requiring reoperations. This research proposal is designed to develop a new leaflet repair patch for pulmonary and aortic valve repair (TxGuard-LP) that allows ease of suturing, resists early degeneration, and allows regeneration with host cells so that the leaflet would grow with the pediatric patient.

Project Terms:
Adolescent; Affect; Age; Age-Years; Anticoagulation; aortic valve; Aortic Valve Stenosis; Autologous; base; biomaterial compatibility; Bioprosthesis device; Blood; Blood Vessels; calcification; Catheterization; Cattle; Cell Wall; Cells; Childhood; Clinical; congenital heart disorder; crosslink; Data; Defect; design; Development; Devices; Diagnosis; Double Outlet Right Ventricle; Ensure; Environment; experience; Failure; Family suidae; Fatigue; flexibility; Fontan Procedure; Future; Geometry; Glucose; Glutaral; Goals; Growth; Heart Valves; hemodynamics; Impairment; implantation; improved; Infant; Infection; infection risk; Inflammation; Inflammatory; Inflammatory Response; Intervention; Legal patent; Life; Longevity; Lung; Mechanics; Mediastinum; Natural regeneration; neonate; Newborn Infant; novel; operation; Operative Surgical Procedures; Patient-Focused Outcomes; Patients; pediatric patients; pericardial sac; Periodicity; Pharmaceutical Preparations; Phase; Population; Predisposition; preservation; Procedures; Property; Protocols documentation; prototype; Pulmonary artery structure; pulmonary valve replacement; Pulmonary valve structure; Rattus; regenerative; Repair Material; repaired; Repeat Surgery; Research Proposals; Resistance; response; Risk; Risk Factors; Safety; Small Business Technology Transfer Research; Stenosis; sterility testing; Sterilization; Structure; Surgeon; Surgical complication; Surgical sutures; Technology; Testing; Tetralogy of Fallot; Thinness; thrombogenesis; Thrombosis; tissue repair; Tissues; valve replacement; viscoelasticity; Xenograft procedure