Congenital heart disease (CHD) is caused by defects in the heart structure that occur at birth and affect blood flow through the heart and the rest of the body. CHD affects around 10 out of 1, 000 live-born children, 25% of which will need an intervention or surgery within their first year of life. Circa 1 million children and 1.4 million adults live with CHD in the US, and over 182, 000 heart valve replacements are performed every year. Currently, available heart valve prostheses do not perform as native cardiac tissue and have several limitations related to their durability and ability to support tissue regeneration. In addition, they have been associated with complications such as clots, increased risk of thrombosis and thromboembolism, calcification, and infection. Replacement of bioprosthetic valves often requires complex and high-risk operations and poses an economic burden of $1.7B in the US per year to the healthcare system. Neoolife aims to overcome these major drawbacks in CHD therapy by developing tissue engineered heart valves (TEHVs) that are fabricated using scaffolds that mimic human tissue. Through endogenous tissue growth, Neoolife's biomimetic pulmonary heart valves are extensively augmented or eventually replaced, leaving autologous and functional leaflets that grow with the CHD pediatric patient that are durable and non- thrombogenic. These biomimetic valves do not require life-long blood thinner treatments and are resistant to calcification and infection. In this STTR Phase I project, Neoolife will modify its proprietary Double Component Deposition (DCD) technology to obtain a more homogeneous biomimetic scaffold deposition. Biomimetic pulmonary heart valve prototypes (n=10) will be fabricated using a new multiple stage processing setup. The prototypes will be tested in vitro for their mechanical and functional properties and assessed in vivo (n=5, 180 days) to evaluate polymer degradation, cellularization, biomechanics, and valve function. In Phase II, further in vitro and in vivo studies will be performed to provide sufficient technical information to demonstrate that Neoolife developed pulmonary heart valve qualifies for obtaining a Humanitarian Device Exemption (HDE) designation for the treatment of pediatric CHD.
Public Health Relevance Statement: NARRATIVE Congenital heart disease (CHD) is the most frequent birth defect that comes with a high risk of requiring life- saving surgery within the first year of the newborn's life. The most common procedure for CHD is pulmonary heart valve replacement, but current valve solutions are inadequate with over 20% of cases needing reoperations within 5 to 15 years of implant. This STTR project will address the limitations of current bioprosthetic valves by developing a biomimetic pulmonary heart valve that successfully mimics human tissue, which will increase the quality of life and decrease the risk of reoperations for pediatric CHD patients. Terms: Birth Defects; Congenital Anatomic Abnormality; Congenital Anatomical Abnormality; Congenital Defects; Congenital Deformity; Congenital Malformation; Congenital Abnormality; 21+ years old; Adult Human; adulthood; Adult; Affect; Anticoagulant Agents; Anticoagulant Drugs; blood thinner; thrombopoiesis inhibitor; Anticoagulants; Antigenic Determinants; Binding Determinants; Epitopes; Aorta; Biocompatible Materials; Biomaterials; biological material; Biomechanics; biomechanical; Bioprosthesis device; Bioprosthesis; Bioprosthetic; Birth; Parturition; Cells; Cell Body; Child; 0-11 years old; Child Youth; Children (0-21); kids; youngster; Echocardiography; Echocardiogram; Transthoracic Echocardiography; heart sonography; Engineering; Freedom; Liberty; Growth; Generalized Growth; Tissue Growth; ontogeny; Healthcare Systems; Health Care Systems; Heart; Cardiac Surgery procedures; Cardiac Surgery; Cardiac Surgical Procedures; Heart Surgical Procedures; heart surgery; Heart Valve Prosthesis; Cardiac Valve Prothesis; artificial heart valves; artificial valves; prosthetic heart valve; Heart Valves; Cardiac Valves; hemodynamics; Hospitalization; Hospital Admission; In Vitro; Newborn Infant; 0-4 weeks old; Newborns; newborn child; newborn children; Infection; Lung; Lung Respiratory System; pulmonary; Marketing; Methods; Legal patent; Patents; Patients; Polymers; polymer; polymeric; Polyurethanes; Ostamer; Pellethane; Polyisocyanates; Pulmonary valve structure; Pulmonary Valve; Pulmonic Valve; Quality of life; QOL; Repeat Surgery; Reoperation; Rest; Risk; Spatial Distribution; Technology; Testing; Thromboembolism; Thrombosis; thrombotic disease; thrombotic disorder; Tissues; Body Tissues; Universities; Surgical Valves; Thrombus; congenital cardiac abnormality; congenital cardiac disease; congenital cardiac disorder; congenital cardiac malformation; congenital heart abnormality; congenital heart anomaly; congenital heart disease; congenital heart malformation; congenital heart disorder; Prosthetic device; Prosthetics; Prosthesis; Calcified; calcification; improved; Procedures; pulmonary trunk valve replacement; pulmonic valve replacement; pulmonary valve replacement; cardiac valve replacement; heart valve replacement; Chronic; Clinical; Phase; Histologically; Histologic; Physiologic; Physiological; Hospitalization cost; Hospital Costs; Evaluation; Failure; pediatric; Childhood; Blood flow; Collaborations; Infiltration; Deposition; Deposit; scaffold; scaffolding; Life; Mechanics; mechanic; mechanical; Complex; Autologous; human tissue; Protocols documentation; Protocol; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Surgeon; success; Animal Model; Animal Models and Related Studies; model of animal; Structure; Devices; bioprocess; Property; Biomimetics; Biological Mimetics; Intervention; Intervention Strategies; interventional strategy; Biomimetic Materials; Thickness; Thick; Coagulation Process; Clotting; Coagulation; valve replacement; Address; Defect; Economic Burden; Qualifying; in vivo; Small Business Technology Transfer Research; STTR; Process; Cardiac; Development; developmental; tissue regeneration; regenerate new tissue; regenerate tissue; regenerating damaged tissue; regenerating tissue; tissue regrowth; tissue renewal; tissue specific regeneration; cost; neglect; designing; design; Coupling; resistant; Resistance; Implant; implantation; develop therapy; intervention development; treatment development; therapy development; prototype; high risk; in vitro testing; operations; operation; child patients; pediatric patients; Structural malformation; structural abnormalities; structural anomalies; Structural defect; in vivo testing; in vivo evaluation; engineered heart tissue; cardiac tissue engineering; thrombogenicity; thrombogenesis; ovine animal model; ovine model; sheep model; regeneration potential; regenerative potential; biomechanical test; biomechanical analyses; biomechanical analysis; biomechanical assessment; biomechanical characterization; biomechanical evaluation; biomechanical measurement; biomechanical profiling; manufacture
