Abstract 4146651: Tissue-Engineered Vascular Grafts: Evaluation of Remodeled Neotissue and Its Effect on Flow Dynamics

Background: The Fontan surgery for treating hypoplastic left heart syndrome has significantly improved postoperative mortality. However, the materials commonly used for conduits, such as PTFE, can cause complications, such as graft calcification over long-term follow-up, which causes flow restriction and lower exercise tolerance as clinical complications. To address these issues, we have developed a tissue-engineered vascular graft (TEVG) composed of biodegradable polymers that are replaced by autologous tissue, called "neotissue," which exhibits histological similarity to native vessels(Figure1) and resistance to calcification. We are investigating the functional properties of this neotissue, focusing on distensibility, an essential function accommodating blood volume, and its impact on flow dynamics. Methods: We evaluated chronic sheep models (6-8 years post-implantation) with thoracic inferior vena cava (IVC) interposition grafts of TEVG (n=5) and PTFE (n=5), as well as age-matched surgically naive sheep (n=5). Using our established in vivo distensibility testing protocol(Figure1b), we measured distensibility in the target regions and compared the groups. Additionally, we utilized the 3D geometries obtained from 3D angiography to create patient-specific computational flow dynamics simulations using a software, SimVascular, allowing us to investigate the impact of distensibility and graft 3D morphology on flow dynamics. Results: Distensibility measurements showed no significant difference between TEVG (173.67±98.74[%100mmHg]) and native vessels (268.57±199.57), while PTFE grafts (10.35±12.67) exhibited significantly lower compliance compared to the other two groups(Figure1). The 3D fluid model simulations generated by SimVascular revealed that the native IVC revealed uniform dilation and smooth blood flows by fluid stress. TEVGs showed small velocity acceleration in the middle. In contrast, since the PTFE grafts were not distensible, they caused significant flow velocity acceleration and high wall shear stress at the graft region(Figure2,3). Conclusions: The TEVG neotissue demonstrated significantly higher distensibility than PTFE grafts and was not significantly different from native vessels. The simulation demonstrated that the differences in distensibility in response to fluid volume impact flow dynamics, which relate to the clinical complications of Fontan patients. TEVG has the potential to mitigate these complications.