6-Month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep |
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| Institution: | 1. Departments of Biomedical Engineering, University of Minnesota, United States;2. Department of Chemical Engineering & Material Science, University of Minnesota, United States;3. Experimental Surgical Services, University of Minnesota, United States;1. Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany;2. Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany;3. Institute of Anatomy, University of Veterinary Medicine Hannover, Germany;1. Biotechnology Graduate Program, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt;2. Biology Department, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt;3. Energy Materials Laboratory (EML), School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt;1. Cardiovascular Research Unit, MRC IUCHRU, University of Cape Town, South Africa;2. Strait Access Technologies Pty Ltd, Cape Town, South Africa;3. Wake Forest Institute of Regenerative Medicine, NC, USA;1. Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy;2. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA;3. Sarver Heart Center, University of Arizona, Tucson, AZ, USA;1. Department of BioMedical Engineering, Saveetha Engineering College, Thandalam, Chennai 602105, India;2. Department of Research & Development, NoobTron Pvt. Ltd., India;3. Department of Mechanical Engineering, Hindustan Institute of Technology & Science, Padur 601103, India |
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| Abstract: | Diseased aortic valves often require replacement, with over 30% of the current aortic valve surgeries performed in patients who will outlive a bioprosthetic valve. While many promising tissue-engineered valves have been created in the lab using the cell-seeded polymeric scaffold paradigm, none have been successfully tested long-term in the aortic position of a pre-clinical model. The high pressure gradients and dynamic flow across the aortic valve leaflets require engineering a tissue that has the strength and compliance to withstand high mechanical demand without compromising normal hemodynamics. A long-term preclinical evaluation of an off-the-shelf tissue-engineered aortic valve in the sheep model is presented here. The valves were made from a tube of decellularized cell-produced matrix mounted on a frame. The engineered matrix is primarily composed of collagen, with strength and organization comparable to native valve leaflets. In vitro testing showed excellent hemodynamic performance with low regurgitation, low systolic pressure gradient, and large orifice area. The implanted valves showed large-scale leaflet motion and maintained effective orifice area throughout the duration of the 6-month implant, with no calcification. After 24 weeks implantation (over 17 million cycles), the valves showed no change in tensile mechanical properties. In addition, histology and DNA quantitation showed repopulation of the engineered matrix with interstitial-like cells and endothelialization. New extracellular matrix deposition, including elastin, further demonstrates positive tissue remodeling in addition to recellularization and valve function. Long-term implantation in the sheep model resulted in functionality, matrix remodeling, and recellularization, unprecedented results for a tissue-engineered aortic valve. |
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| Keywords: | Tissue engineering Heart valve Aortic valve disease Decellualrized biomaterial Matrix remodeling |
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