Cardiovascular disease is a leading cause of death in the US, Europe and Japan and is comprised of a widerange of pathologies. One of the most common procedures is heart valve replacement and is required when thevalve fails due to regurgitation or is unable to open fully during the cardiac cycle. Causes include congenitaldefects, calcification and prolapse, but regardless of origin there are limited options to repair valves and surgicaltreatments are focused primarily on replacement. It is estimated that each year more than 150,000 patientsreceive heart valve replacements at a mean cost of ~$200,000 per procedure, corresponding to >$30B cost tothe healthcare system. The heart valve market has continued to grow over the past decade due to advances insurgical and minimally-invasive technologies associated with heart valve placement. However, current valvesrepresent some compromise in fit, biological performance, durability and surgical procedure, with uniqueadvantages and disadvantages associated with current mechanical and bioprosthetic heart valves. In thisproposal our objective is to develop a new bioprosthetic heart valve using advanced manufacturing approachesthat has the durability of mechanical valves, the non-thrombogenicity of biologic valves, the soft deformability forminimally-invasive transcatheter delivery, and the ability to custom fit the anatomy of any patient. To do thisFluidForm, Inc in collaboration with Carnegie Mellon University will develop a new freeform reversible embeddingof suspended hydrogels (FRESH) 3D printed heart valve using collagen type I that recreates the laminar andanisotropic extracellular matrix (ECM) architecture in native valves. Our preliminary data shows that FRESH 3Dprinting can be used to manufacture functional tri-leaflet heart valves entirely from collagen and can supportphysiologic flow rates and pressure for short periods of time. Here we will improve valve performance byrecreating the collagen fiber arrangement and mechanical properties in native valve leaflets via two researchaims. First, we will demonstrate that FRESH 3D printing of collagen type I can recreate the collagen fiberarchitecture in the different layers of the native aortic valve leaflets with <10% difference in mean orientationangle. Second, we will prove that FRESH 3D printed collagen valve leaflets can be engineered to have radialand circumferential elastic modulus, non-linear stress-strain response, creep, and fatigue life within 75% of nativeaortic valve leaflets. Phase I proof-of-concept success will provide a strong foundation for a Phase II SBIR projectthat will validate the complete FRESH printed, bioprosthetic aortic valve in an in vitro flow system that simulateshuman pressure and flow rate and in a pre-clinical ovine model to assess hemocompatibility and biologicalresponse.
Public Health Relevance Statement: Each year more than 150,000 patients receive a replacement heart valve at a mean cost of ~$200,000 per
procedure, corresponding to >$30B cost to the healthcare system. However, current valves represent some
compromise in fit, biological performance, durability and surgical procedure, and some patients are not
candidates due to high surgical risk. Here we will develop a new bioprosthetic heart valve using advanced
manufacturing approaches that has the durability of mechanical valves, the blood compatibility of biologic valves,
the soft deformability for minimally-invasive transcatheter delivery, and the ability to custom fit the anatomy of
any patient.
Project Terms: Congenital Abnormality ; Birth Defects ; Congenital Anatomic Abnormality ; Congenital Anatomical Abnormality ; Congenital Defects ; Congenital Deformity ; Congenital Malformation ; Anatomy ; Anatomic ; Anatomic Sites ; Anatomic structures ; Anatomical Sciences ; Anticoagulation ; aortic valve ; aortic valve replacement ; Architecture ; Engineering / Architecture ; Bioprosthesis device ; Bioprosthesis ; Bioprosthetic ; Blood ; Blood Reticuloendothelial System ; Cardiovascular Diseases ; cardiovascular disorder ; Cattle ; Bovine Species ; bovid ; bovine ; cow ; Cause of Death ; Clinical Trials ; Collagen ; Disadvantaged ; Engineering ; Europe ; Extracellular Matrix ; Cell-Extracellular Matrix ; ECM ; Fatigue ; Lack of Energy ; Foundations ; Healthcare Systems ; Health Care Systems ; Cardiac Surgery procedures ; Cardiac Surgery ; Cardiac Surgical Procedures ; Heart Surgical Procedures ; heart surgery ; Heart Valves ; Cardiac Valves ; Artificial Heart ; cardiac prosthesis ; heart prosthesis ; mechanical heart ; prosthetic heart ; Human ; Modern Man ; In Vitro ; Japan ; Metals ; Methods ; Muscle ; Muscle Tissue ; muscular ; Pathology ; Patients ; Periodicity ; Cyclicity ; Rhythmicity ; Polymers ; pressure ; Printing ; Ptosis ; Procidentia ; Prolapse ; Research ; Science ; Stress ; Family suidae ; Pigs ; Suidae ; Swine ; porcine ; suid ; Technology ; Testing ; Time ; Collagen Type I ; Type 1 Collagen ; Universities ; Work ; pyrolytic carbon ; LTIC ; low temperature isotropic carbon ; Custom ; calcification ; Calcified ; base ; crosslink ; cross-link ; improved ; Procedures ; heart valve replacement ; cardiac valve replacement ; repaired ; repair ; Phase ; Biological ; Physiological ; Physiologic ; Chemicals ; Collagen Fiber ; Fiber ; Failure ; Funding ; Collaborations ; Letters ; Intellectual Property ; Shapes ; Life ; mechanical ; Mechanics ; Complex ; Radius ; Radial ; Source ; System ; 3-D ; 3D ; three dimensional ; 3-Dimensional ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; Performance ; success ; Hydrogels ; Structure ; Devices ; response ; Biological Mimetics ; Biomimetics ; Thickness ; Thick ; Data ; Harvest ; in vivo ; Filament ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Process ; Ventricular ; Cardiac ; pre-clinical ; preclinical ; cost ; design ; designing ; innovation ; innovate ; innovative ; Implant ; implantation ; commercialization ; minimally invasive ; patient population ; manufacturing scale-up ; 3D Print ; 3-D print ; 3-D printer ; 3D printer ; 3D printing ; three dimensional printing ; pediatric patients ; child patients ; bioprinting ; bio-printing ; mechanical properties ; Modulus ; phase 1 testing ; phase 1 evaluation ; phase I evaluation ; phase I testing ; hemocompatibility ; surgical risk ; surgery risk ; sheep model ; ovine animal model ; ovine model ;
