C2 6085 Disclaimer — This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on publicly available information and may not be provide complete analyses of all relevant data. If this paper is used for any purpose other than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at the University of Pittsburgh Swanson School of Engineering, the user does so at his or her own risk. STEM CELL-BASED TISSUE ENGINEERED VASCULAR GRAFT Abigail Snyder, ams528@pitt.edu, Mahboobin 10:00, Zachary Mattis, zmm15@pitt.edu, Mahboobin 10:00 Revised Proposal — Tissue engineered vascular grafts are an innovation that demonstrates cutting-edge stem cell technology by utilizing the patient’s own personal mesenchymal cells in order to grow a suitable vascular graft. This graft can be incorporated into a patient's circulatory system to mimic the vasoreactivity and biomechanics of the native vasculature, while maintaining long-term patency within the patient [1].The great leaps in the field of cellular research has allowed for the development of new and improved techniques to develop the tissue engineered vascular graft (TEVG). The process to construct the TEVG begins by extracting the mesenchymal cells from the patient. These cells are then seeded onto a polymer scaffolding that will serve as the original structure for the graft. After several months of allowing the cells to multiply and grow, the graft is then surgically implanted in place of a diseased artery. The graft continues to grow in vivo until it is a functioning, living tissue that can grow and remodel along with the rest of the body. Research for the TEVG is rapidly progressing due to the dire need for the innovation in clinical use. As stated in the World Journal of Surgery, “Cardiovascular disease, including coronary artery and peripheral vascular pathologies, is the leading cause of mortality in the United States and Western countries” [2]. The demand for a suitable graft during bypass surgeries and other vascular reconstructive surgeries is very high in an effort to try and reduce the number of deaths each year due to cardiovascular disease. Current grafting choices all include options that require multiple follow-up surgeries to replace the old graft used in pervious procedures. In children who need a vascular conduit during pediatric congenital heart surgery, their condition means a lifetime of being in and out of hospitals. However, this TEVG has the ability to “produce tissues that can grow, remodel, rebuild, and respond to injury” [3] making it better than all the other current options. This new innovation is a necessary advancement that when fully developed has the ability to help improve the lives of thousands of people and potentially save just as many lives. Our plan moving forward is to specifically look for research articles that discuss the different procedural aspects of this technology such as the different types of cells used to seed the scaffolding, as well as different types of biomaterials that can be used to form the biodegradable scaffolding. We plan on beginning our paper by explaining the development and process of making the TEVG, followed by a discussion on University of Pittsburgh Swanson School of Engineering 1 2016/01/29 the other current options for a vascular graft currently in use. Additionally, we are very interested in the potential that this type of technology has on other aspects of the medical community, such as the different types of diseases and medical conditions that could utilize the TEVG. There are many medical journal articles that can be used to look into these matters. We plan on finishing the paper with the societal implications and benefits of this innovation to the public. In order to gain first-hand knowledge of this innovation, we have organized an interview with Dr. Vorp, head of the Vascular Tissue Vorp Lab here at the University of Pittsburgh. This lab focuses on vascular bioengineering research projects, including a current project that focuses exclusively on TEVG research. REFERENCES [1] M. Cleary, E. Geiger, C. Grady, C. Best, Y. Naito, C. Breuer. (2012). “Vascular tissue engineering: the next generation”. US National Library of Medicine National Institutes of Health. (Online Article). http://www.ncbi.nlm.nih.gov/pubmed/22695236 [2] X. Wang, P. Lin, Q. Yao, C. Chen. (2007). “Development of Small-Diameter Vascular Graft”. World Journal of Surgery. (Online Article). http://www.ncbi.nlm.nih.gov/pubmed/17345123 [3] Shannon L. M. Dahl. (2011). “Readily Available TissueEngineered Vascular Grafts”. Science Translational Medicine. (online article). http://www.perruchenautomne.eu/biblio/readily%20availabl e%20tissue%20enineered%20vascular%20graft%20science %20translationnal%20med%202011.pdf ANNOTATED BIBLIOGRAPHY C. Mitcham. (2005). “Bioengineering Ethics”. Encyclopedia of Science Technology and Ethics. (Encyclopedia). The Encyclopedia of Science Technology and Ethics provides an unbiased perspective on the direct laws of ethics that must be followed when pursuing the field of bioengineering. As the innovative TEVG deals with stem cell manipulation of humans, it is evident that some ethical questions will be raised. This document will allow us to Snyder Mattis clearly and informatively address the ethical concerns associated with the TEVG. is uniquely demonstrates implanting a TEVG in a lamb and an in vivo monitoring system as well. This will be an integral part of our discussion of current testing and measurement methods of the TEVG. H. Kurobe, M. Maxfield, C. Breuer, T. Shinoka. (2012). “Concise Review: Tissue-Engineered Vascular Grafts for Cardiac Surgery: Past, Present, and Future.” Stem Cells Translational Medicine. (Online article). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659720/ This article, from the journal of Stem Cells and Translational Medicine, specializes in the history as well as past accomplishments of the TEVG, including the first preclinical tests on different types of animals. This progressed into the first FDA approved clinical trial for pediatric cases. This information helps give us a history of the TEVG, demonstrates how far the TEVG innovation has progressed, and shows the potential it holds for the future. S. L. M. Dahl. (2011). “Readily Available Tissue-Engineered Vascular Grafts”. Science Translational Medicine. (online article). http://www.perruchenautomne.eu/biblio/readily%20availabl e%20tissue%20enineered%20vascular%20graft%20science %20translationnal%20med%202011.pdf Published by the American Association for the Advancement of Science, the Science Translational Medicine magazine is a research article extensively detailing the experiments and trials that have already been performed involving the TEHV. This source’s research information regarding preclinical testing will be vital for our paper as we discuss the progress and success the TEHV has had in the past. J. Patterson, T. Gilliland, M. Maxfield, S. Church, Y Naito, T. Shinoka, C. Breuer. (2012). “Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again.” US National Library of Medicine National Institutes of Health. (Online Article). http://www.ncbi.nlm.nih.gov/pubmed/22594331 Taken from the National Library of Medicine National Institutes of Health, this academic article describes the condition known as congenital heart defect (CHD) in pediatric cases. It is one of the main conditions that the TEVG will be able to help treat after its development. We intend on performing a comprehensive analysis of this disease, as well as on the treatment process for children that have CHD. T. Shin’oka , G. Matsumura, N. Hibino, Y. Naito, M. Watanabe, T. Konuma, T. Sakamoto, M. Nagatsu, H. Kurosawa. (2005). “Midterm clinical result of tissueengineered vascular autografts seeded with autologous bone marrow cells.” The Journal of Thoracic and Cardiovascular Surgery. (Online Article). http://www.sciencedirect.com/science/article/pii/S00225223 05001297 Published in the Journal of Thoracic and Cardiovascular Surgery, this academic research article provides a full account of clinical midterm results of the TEVG seeded by bone marrow cells. This specific type of cell is one of the possibilities that can be seeded onto the TEVG scaffolding. These halfway results will provide the foundation for our section that describes the models utilizing mesenchymal bone marrow cells. M. Cleary, E. Geiger, C. Grady, C. Best, Y. Naito, C. Breuer. (2012). “Vascular tissue engineering: the next generation”. US National Library of Medicine National Institutes of Health. (Online Article). http://www.ncbi.nlm.nih.gov/pubmed/22695236 This academic article published by the US National Library of Medicine National Institute of Health. This article thoroughly describes precisely how the TEVG are made as well as the different methods and materials that can be used to create them. This information will be effective as we describe the primary method of construction, and later as we specify the different types of biomaterials that are available to be used. X. Wang, P. Lin, Q. Yao, C. Chen. (2007). “Development of Small-Diameter Vascular Graft”. World Journal of Surgery. (Online Article). http://www.ncbi.nlm.nih.gov/pubmed/17345123 The scholarly article on the development of small diameter vascular grafts was not only printed in the World Journal of Surgery, but it was also presented at the Molecular Surgeon Symposium on vascular conditions. The paper not only describes the TEVG, but also explores other options for alternatives of vascular grafts. These alternatives will allow us to illustrate the superiority of the TEHV. M. T. Koobatian, C. Koenigsknecht, S. Row, S. Andreadis D. Swartz. Surgical Technique for the Implantation of Tissue Engineered Vascular Grafts and Subsequent In Vivo Monitoring. J. Vis. Exp. (98), e52354, doi:10.3791/52354 (video) http://www.jove.com/video/52354/surgicaltechnique-for-implantation-tissue-engineered-vascular-grafts (2015). This video was made by the University of Buffalo’s School of Medicine. Funded by the National Heart and Lung Institute, the University directed research for surgical implantation and in vivo monitoring of the TEVG. This video 2