Patient Specific Tissue Engineered Vascular Graft Creation Using 3D Printing Technology

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Congenital heart disease (CHD) is the leading cause of death associated with congenital anomalies. Despite significant advances in surgical management for CHD, one significant source of morbidity and mortality arises from the complexity of surgery for the diverse anatomies. Previous studies demonstrated that the ideal design of reconstruction for stenosis or hypoplastic vessels during surgery is important to reduce energy loss and undesirable flow inside of graft. However, surgeons have no information of flow dynamics and hemodynamics data of the reconstructed route during procedure because the surgical field needs to be bloodless. Therefore, ensuring a patient-specific graft design for ideal reconstructed route before surgery with a balanced flow distribution and minimum energy loss may yield long-term benefits for patient health and quality of life. The goal of this proposal is to demonstrate our integrated approach of recent progress in 3D imaging, 3D printing, and tissue engineering technology can create pre-surgically designed patient- specific vascular graft that can promote optimal neovessel formation with growth over time. We have demonstrated native vessel like neotissue formation of tissue engineered vascular graft (TEVG) using FDA approved biomaterials of PGA/PCLA in small and large animal studies. Based on these experiences, we have developed novel 3D printing technology combining 3D printed metal mandrels with nanofiber electrospun technology. With this 3D printing technology, we showed that straight conduit shaped TEVG developed native like neovessel formation in a sheep model. For this next step, we aim to develop TEVG with complex shapes that can be applied to real patients with complex anatomy. We hypothesized that patient-specific TEVG made of nanofiber PGA/PCLA using our 3D printing technology can be designed using CAD with pre- operative imaging and flow dynamics data, and demonstrate proper neotissue formation with growth over time. To this end, in R21 phase, 1) we will optimize patient-specific creation of 3D printed vascular grafts and test In-vitro and 2) We will determine if the estimated flow dynamics analysis of pre-operative design can match with the performance of actual 3D printed grafts using short-term in vivo model. In R33 phase, we will determine if the estimated flow dynamics of pre-operative design can be preserved in growing neotissue after degradation of graft using long-term animal model. This project will be an important step towards clinical application of patient-specific vascular grafts that recapitulate the native anatomy and mechanical properties. The results of this work will have a broader impact on the design and fabrication of other more complex cardiovascular structures for implantation. This paradigm shift in vascular graft technology will improve the quality and safety of pediatric patient care.