Using Three-Dimensional Bioprinting To Create Vascular Grafts: A Pilot Study
Gulus Emre, Yale UniversityFollow
Date of Award
January 2017
Document Type
Thesis
Degree Name
Medical Doctor (MD)
Department
Medicine
First Advisor
John P. Geibel
Abstract
Our hypothesis was that vascular grafts could be created using three-dimensional (3D) bioprinting technology. Our goal was to create vascular grafts that could be implanted as a patch into a rat vessel without rupture or occlusion. We utilized printing technology from Organovo to 3D print vascular graft material consisting of rat smooth muscle cells, rat fibroblast cells, gelatin and a hydrogel mixture. Our vascular grafts were printed as tubular structures with an internal diameter of 3mm. After a period of maturation (7-12 days), a segment of the print was cut out and used to repair an arteriotomy or venotomy created in rat aorta or inferior vena cava, respectively. We found that the animals survived and that the grafts remained in place without evidence of rupture or stenosis over the course of 30 days. Animals were sacrificed 7 days or 30 days after implantation to evaluate how the graft changes over time; histological examinations of the patched vessels suggest that the patch adapts to the host site and does not induce a major inflammatory response. Although more work is needed to further characterize the behavior of these patches in vivo, our results demonstrate that 3D bioprinting is a viable option for creating vascular patch grafts.
Methuselah Foundation Provides Generous Gift to Support Collaboration
SAN DIEGO, NEW HAVEN, Conn. and SPRINGFIELD, Va., Dec. 3, 2014 /PRNewswire/ -- Organovo Holdings, Inc. (NYSE MKT: ONVO) ("Organovo"), a three-dimensional biology company focused on delivering breakthrough 3D bioprinting technology, and Yale School of Medicine, Department of Surgery have formed a collaboration to develop bioprinted tissues for surgical transplantation research, made possible by a generous gift from the Methuselah Foundation.
At any given time, the waiting lists for critical organ transplants are three to five times as long as the list of available organs. In addition, other transplantable tissues, such as blood vessels, lung, and bone, are also in high demand with few sources.
"Developing organs for surgical implantation will take meaningful efforts and focused partnerships. This collaboration with Yale, which combines their expertise and technology with our own, is one important step in progressing towards implantable, therapeutic tissues," said Keith Murphy, chairman and CEO of Organovo. "We are grateful to the Methuselah Foundation for their generous gift that gives those working towards significant breakthroughs in organ bioprinting an opportunity to use the NovoGen bioprinter and enable greater access to Organovo's powerful platform."
The fast-growing field of tissue engineering developed to address the shortage of tissues available for repair and transplantation. At Yale's School of Engineering & Applied Science and Yale's Department of Surgery clinicians and basic scientists are working to combine tissue engineering technologies with medical therapies.
"We are excited to begin this collaboration with Organovo and are honored to be part of Methuselah's University 3D Bioprinter Program, which gives our key researchers access to cutting-edge 3D bioprinting technology," said Dr. John Geibel, Vice Chairman, Director of Surgical Research, and Professor of Surgery and Cellular and Molecular Physiology at Yale University. "This collaboration is a great way to bring the best minds of both worlds to solve a major research and medical goal – using bioprinting to produce transplantable tissues."
Under Methuselah's University 3D Bioprinter Program, Methuselah is donating at least $500,000 in direct funding to be divided among several institutions for Organovo bioprinter research projects. This funding will cover budgeted bioprinter costs, as well as other aspects of project execution.
"We at the Methuselah Foundation have been a long-time supporter of academic and industry research in 3D bioprinting, regenerative medicine, and tissue engineering," said David Gobel, CEO of the Methuselah Foundation. "Our University 3D Bioprinter Program puts Organovo's breakthrough 3D bioprinting technology in the hands of the brightest scientists at tissue engineering centers of excellence."
About Yale School of Medicine
Founded in 1810, the Yale School of Medicine is a world-renowned center for biomedical research, education and advanced health care. Among its divisions are one of the nation's oldest schools of public health and the internationally recognized Child Study Center, founded in 1911. Its Yale Cancer Center is one of 41 comprehensive cancer centers designated by the National Cancer Institute. Its 33 academic departments include 11 in the basic sciences, 19 in clinical fields, and 5 in public health. The School of Medicine has made major contributions to public health by isolating the polio virus, promoting the early use of cancer chemotherapy, adding to the arsenal of AIDS medications, developing a promising Lyme disease vaccine, discovering genes that contribute to skin cancer and high blood pressure, and making breakthroughs in the treatment of Parkinson's disease, depression and other mental disorders. The School of Medicine consistently ranks among the handful of leading recipients of research funding from the National Institutes of Health and other organizations supporting the biomedical sciences.
About Methuselah Foundation
The Methuselah Foundation is a non-profit medical charity working to create a world where 90 year olds can have the health profile of 50 year olds, by 2030. By opportunistically leveraging resources, enabling partnerships, and awarding prizes and grants, we accelerate disruptive developments in biomedical engineering that will eradicate needless suffering and extend healthy human life. For more information please visit: www.methuselahfoundation.org and www.neworgan.org.
About Organovo Holdings, Inc.
Organovo designs and creates functional, three-dimensional human tissues for use in medical research and therapeutic applications. The Company develops 3D human disease models through internal development and in collaboration with pharmaceutical and academic partners. Organovo's 3D human tissues have the potential to accelerate the drug discovery process, enabling treatments to be developed faster and at lower cost. The company recently launched its initial product of the planned exVive3DTM portfolio offering, a 3D Human Liver Tissue for use in Toxicology and other preclinical drug testing. Additional products, including a 3D Kidney Model, are in development with anticipated release for use in the latter half of calendar year 2016. The company also actively conducts early research on specific tissues for therapeutic use in direct surgical applications. In addition to numerous scientific publications, the Company's technology has been featured in The Wall Street Journal, Time Magazine, The Economist, and numerous others. Organovo is changing the shape of medical research and practice. Learn more at www.organovo.com.
