All present day prosthetic heart valves suffer from complications. Mechanical heart valves (HVs) require life-long anti-coagulation therapy, while bioprosthetic heart valves based on fixed tissue are plagued with durability, immunogenic and calcification issues. Polymeric heart valves promise to combine the best of the mechanical valves and the best of the bioprosthetic heart valves. Our lab has developed a novel biomaterial, BioPoly, made of engineering polymers that are, at a molecular level, interlocked with hyaluronan (HA, a naturally occurring polysaccharide) to make highly hydrophilic hemocompatible polymer leaflets with the durability of engineered synthetic polymers. Preliminary work has shown that BioPoly leaflets have remarkably reduced thrombogenic potential relative to plain polymer leaflets. Further, we have already demonstrated the feasibility of manufacturing BioPoly leaflets and assembling them into an implantable trileaflet valve. The present R01 study aims to gauge the efficacy of BioPoly as a potential alternative to current heart valve technology by fine tuning material composition and processing to meet the durability and antithrombogenic requirements for heart valve leaflets. Our central hypothesis is: BioPoly HVs offer a viable solution to the drawbacks of both bioprosthetic and mechanical HVs. This is tested in three aims.
Aim 1 quantifies heart valve hemodynamic performance and the durability/fatigue characteristics of BioPoly heart valves.
Aim 2 focuses on elucidating the effects of leaflet composition and processing on hemocompatibility.
Aim 3 focuses on understanding the in vivo hemocompatibility and calcification properties of BioPoly HV. This proposal is led by Dr. Lakshmi Prasad Dasi, who is a well-trained young investigator with expertise in heart valve engineering and cardiovascular biomechanics. Co-investigators are Dr. James, who is an established polymer materials scientist, and the inventor of BioPoly. She has successfully translated this material in orthopedic applications (currently commercially available in Europe); Dr. Popat whose expertise lies in bio-compatibility and surface nano-engineering; and Dr. Orton an experienced Veterinary cardiothoracic surgeon. If the proposed work demonstrates that BioPoly leaflet HVs are antithrombogenic, elicit excellent hemodynamics, are durable, and demonstrate resistance to in vivo calcification, this R01 grant may lead to breakthrough technology for polymeric HVs that require little or no anticoagulation, can be delivered minimally invasively and are durable enough to last a lifetime.
The objective of this project is to develop an advanced polymeric heart valve that is engineered for maximum blood compatibility through the use of cross-linked hyaluronan, which is present in all tissues. State-of-the-art manufacturing, experimental studies in the areas of mechanics and materials sciences are utilized to construct this novel heart valve. The proposed innovative approach combines these methods and techniques to optimize a highly innovative concept in a unique interdisciplinary effort to produce durable and highly functional polymeric heart valves. This novel technology will lead to a dramatic improvement in heart valve technology.
|Hatoum, Hoda; Yousefi, Atieh; Lilly, Scott et al. (2018) An in vitro evaluation of turbulence after transcatheter aortic valve implantation. J Thorac Cardiovasc Surg 156:1837-1848|
|Hatoum, Hoda; Dasi, Lakshmi P (2018) Reduction of Pressure Gradient and Turbulence Using Vortex Generators in Prosthetic Heart Valves. Ann Biomed Eng :|
|Hatoum, Hoda; Dollery, Jennifer; Lilly, Scott M et al. (2018) Impact of patient-specific morphologies on sinus flow stasis in transcatheter aortic valve replacement: An in vitro study. J Thorac Cardiovasc Surg :|
|Hatoum, Hoda; Dollery, Jennifer; Lilly, Scott M et al. (2018) Effect of severe bioprosthetic valve tissue ingrowth and inflow calcification on valve-in-valve performance. J Biomech 74:171-179|
|Hatoum, Hoda; Moore, Brandon L; Dasi, Lakshmi Prasad (2018) On the Significance of Systolic Flow Waveform on Aortic Valve Energy Loss. Ann Biomed Eng 46:2102-2111|
|Hatoum, Hoda; Dollery, Jennifer; Lilly, Scott M et al. (2018) Sinus Hemodynamics Variation with Tilted Transcatheter Aortic Valve Deployments. Ann Biomed Eng :|
|Simon-Walker, Rachael; Cavicchia, John; Prawel, David A et al. (2018) Hemocompatibility of hyaluronan enhanced linear low density polyethylene for blood contacting applications. J Biomed Mater Res B Appl Biomater 106:1964-1975|
|Hatoum, Hoda; Heim, Frederick; Dasi, Lakshmi Prasad (2018) Stented valve dynamic behavior induced by polyester fiber leaflet material in transcatheter aortic valve devices. J Mech Behav Biomed Mater 86:232-239|
|Hatoum, Hoda; Dollery, Jennifer; Lilly, Scott M et al. (2018) Implantation Depth and Rotational Orientation Effect on Valve-in-Valve Hemodynamics and Sinus Flow. Ann Thorac Surg 106:70-78|
|Dasi, Lakshmi P; Hatoum, Hoda; Kheradvar, Arash et al. (2017) On the Mechanics of Transcatheter Aortic Valve Replacement. Ann Biomed Eng 45:310-331|
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