Pulmonary valved conduit xenograft with regeneration potential

具有再生潜力的肺动脉瓣导管异种移植物

• 批准号: 10491195
• 负责人: Ajay Houde
• 金额: $ 104.2万
• 依托单位: ANNOVIANT, INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-03-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10491195
• 关键词: Affect; Anastomosis - action; Aneurysm; Aortic Valve Stenosis; Arteries; Bacteria; Bioreactors; Blood Vessels; Brain; Caliber; Cattle; Cells; Cellular Infiltration; Chronic; Clinical; Data; Defect; Development; Devices; Dilatation - action; Distal; Double Outlet Right Ventricle; Drops; Elastases; Extravasation; Failure; Fatigue; Fontan Procedure; Glucose; Glutaral; Goals; Growth; Image; In Vitro; Infant; Infection; Infectious Agent; Inflammation; Kidney; Legal patent; Liver; Lung; Mechanics; Mediastinum; Membrane; Methods; Mycoplasma; Natural regeneration; Newborn Infant; Operative Surgical Procedures; Organ; Patients; Peracetic Acid; Performance; Pericardial body location; Phase; Population; Preclinical Testing; Predisposition; Procedures; Pseudoaneurysms; Pulmonary valve structure; Pulsatile Flow; Quality Control; Quality of life; Reaction; Repeat Surgery; Reporting; Research Proposals; Resistance; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Spleen; Stenosis; Sterility; Sterilization; Structure; Structure of jugular vein; Surgeon; Technology; Testing; Tetralogy of Fallot; Thick; Thinness; Thrombosis; Thymus Gland; Tissues; Toxic effect; Tube; Validation; Velocimetries; Xenograft procedure; base; biomaterial compatibility; calcification; clinical practice; collagenase; congenital heart disorder; crosslink; dacron; design; feasibility testing; flexibility; fungus; homograft; implantable device; implantation; improved; in vivo; in vivo evaluation; infection risk; mechanical properties; neonate; non-Native; novel; operation; particle; pediatric patients; pre-clinical; pressure; prototype; pulmonary valve replacement; reconstruction; regeneration potential; repaired; sheep model; stability testing; subcutaneous; thrombogenesis; viscoelasticity

Congenital heart disease affects approximately 40,000 newborns each year in the U.S. Valve and conduit replacements are needed for absent pulmonary valve, aortic stenosis (Konno procedure, Ross procedure), double outlet right ventricle (Rastelli operation), extracardiac conduit (Fontan operation), pulmonary valve replacement (Tetralogy of Fallot). Materials in current use include homograft blood vessels; glutaraldehyde treated bovine jugular veins (BJV, Contegra), polytetrafluorethylene (PTFE), and woven or knitted Dacron tubes. 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. In Phase I STTR, we tested the feasibility of a prototype from decellularized and pentagalloyl glucose (PGG) stabilized novel BJV valved conduit device (TxGuard) to augment the already recognized qualities of BJV. All the preclinical testing shows that TxGuard valved conduit is viscoelastic, biocompatible, resists calcification, and thrombosis while allowing host cellular infiltration and the potential for remodeling and growth. To commercialize the TxGuard conduit, we need to obtain data under GMP and GLP conditions that can be submitted to the FDA for HDE application. Towards this goal, we propose the following specific aims for SBIR Phase II. Aim 1: Implement quality control SOPs documents for processing of the TxGuard conduit under GMP, Aim 2: Validate sterilization, packaging, and storage of the TxGuard conduits, Aim 3: Test hydrodynamic performance and fatigue resistance of TxGuard conduits, Aim 4: Perform long-term preclinical in-vivo testing for TxGuard conduits. The ovine model of TxGuard pulmonary valved conduit placement (n=6) will be conducted for 150 days in growing lambs and compared to the clinically available Contegra BJV conduits (n=3) under GLP conditions for FDA submission. The proposed Phase II SBIR project will spearhead the development of a novel BJV device (TxGuard) that would repopulate with host cells and slowly regenerate and grow with the patient without unwanted inflammation and degeneration in contrast to the existing devices.

在美国，先天性心脏病每年影响大约4万名新生儿