Status: Funded - Open
Nanofiber tissue engineered vascular grafts for complex shapes using 3D printing technology
Narutoshi Hibino, M.D., Ph.D.
BACKGROUND: Congenital heart disease is the leading cause of death associated with congenital anomalies affecting nearly 40,000 children each year. Despite significant advances in surgical management for congenital heart disease (CHD), one significant source of morbidity and mortality arises from the use of synthetic biomaterials for various reconstructive cardiac operations. GAP: Tissue engineered vascular grafts (TEVGs) offer a potential strategy for overcoming complications from the use of synthetic biomaterials by providing a scaffold for the patient’s own cells to proliferate and provide physiologic functionality, but current TEVGs are only available in straight segments and do not directly address the diverse shape of vascular anatomy that surgeons routinely need to construct during surgery in a limited time to fulfill the needs of each patient. This study will address the primary research gap between uniform, straight segments of TEVGs and patient specific diverse shapes of TEVGs using 3D printing technology of biomaterials combined with imaging technologies such as ultrasound, CT, and MRI. The most important issue that needs to be overcome for the development of 3D printing TEVG is the material. The biodegradable material that can be used for 3D printing is currently very limited.
HYPOTHESIS: We hypothesized that a patient-specific vascular graft with a complex shape that matches the native vessel profile can promote and support neotissue growth and can be designed and printed from the pre- operative CT/MRI images using 3D printing technology. In order to develop this technology we investigated new materials that can be applied to 3D printing TEVG creation.
METHODS: The patient-specific PCL/CS nanofiber scaffold will be created using the mold designed by CAD software from the image of preoperative CT/MRI scan, and will be evaluated using sheep model.
RESULTS: The graft was designed and created based on pre-surgery imaging using PCL-CS nanofiber. Healthy juvenile sheep (20-30kg) was used in this study (N=6). The animals were sacrificed, and grafts were explanted at six months. There was no aneurysm formation or calcification in the TEVG. Four out of six grafts (67%) were patent. Remaining scaffold area after 6 months in vivo was 9.1%. Histological analysis of patent grafts demonstrated deposition of extracellular matrix constituents including elastin and collagen production, as well as endothelialization and organized contractile smooth muscle cells, similar to that of native carotid artery (CA). The mechanical properties of TEVG were comparable to native CA. There was a significant positive correlation between TEVG wall thickness and CD68+ macrophage infiltration into the scaffold (R2 = 0.95, p = 0.001).
IMPACT: Our study developed novel aortic electrospun TEVGs made from 3D printed custom made mandrels. This is the first step towards making other more complex cardiovascular patient-specific structures that recapitulate the native architecture and mechanical properties, and will improve the quality and safety of pediatric patient care.