1 The goal of this study is to create patient-specific, hemodynamically optimized, tissue engineered 2 vascular grafts (TEVG) for use in aortic arch repair surgery. These TEVGs are optimized for high pressure 3 circulation using 3D printing technology and artificial intelligence, and will grow with the patient, in hopes of 4 obviating need for future surgeries to replace grafts, which can occur with contemporary arch reconstruction 5 materials. Congenital heart disease (CHD) is the leading cause of death due to congenital anomalies. Despite 6 significant advances in surgical management for CHD, one significant source of morbidity and mortality arises 7 from the complexity of surgery for diverse anatomies in the aortic arch. Previous studies have demonstrated 8 that the resultant arch geometry after surgical reconstruction of stenotic or hypoplastic aortas is important to 9 minimize reduce energy loss and undesirable flow inside the arch, which can lead to hypertension, abnormal 10 vascular response and ventricular dysfunction. Ensuring a patient-specific graft design for ideal reconstructed 11 route before surgery with minimum energy loss and wall shear stress may yield long-term benefits for patient 12 health and quality of life. 13 We have demonstrated native vessel like neotissue formation of TEVG in small and large animal 14 studies. Based on these experiences, we have developed a novel 3D printing technology combining 3D printed 15 metal mandrels with nanofiber electro-spun technology. With this 3D printing technology, we showed that 16 TEVG developed native like neovessel formation in venous circulation in a sheep model. For this next step, we 17 aim to develop grafts in arterial circulation that can be applied to aortic reconstruction. We will also develop 18 automatic design algorithms to design optimal graft shape in order to reduce time and cost of patient specific 19 design. We hypothesize that patient-specific TEVG using our 3D printing technology can be designed, 20 aided by pre-operative imaging and flow data, computer assisted design (CAD), automatic design 21 algorithms based on computation fluid dynamics (CFD) results, and will demonstrate proper neotissue 22 formation and growth while maintaining optimally designed hemodynamics. 23 This project will be an important step towards clinical application of patient-specific vascular grafts that 24 recapitulate the native anatomy and mechanical properties. The results of this work will have a broader impact 25 on the design and fabrication of other more complex cardiovascular structures for implantation. This paradigm 26 shift in vascular graft technology will improve the quality and safety of pediatric patient care.

Public Health Relevance

The goal of this study is to create patient-specific, hemodynamically optimized, tissue engineered vascular grafts using 3D printing technology and artificial intelligence for use in aortic arch repair surgery which demands a structured surgical approach in order to optimize hemodynamics postoperatively. We will optimize the design of an aortic graft automatically using computational flow dynamics, refine 3D printing manufacturing, evaluate grafts with in-vitro testing, and finally will test the performance of the grafts in vivo over time. This paradigm shift in vascular graft technology will improve the quality, safety and longevity of pediatric cardiovascular care.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL143468-01
Application #
9580526
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lundberg, Martha
Project Start
2018-07-01
Project End
2022-03-31
Budget Start
2018-07-01
Budget End
2019-03-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205