Preclinical Assessment of a Compliance Matched Biopolymer Vascular Graft - Diversity Supplement

PROJECT ABSTRACT Cardiovascular diseases (CVDs) stand as the primary contributor to global mortality and play a significant role in diminishing the quality of life. The growing incidence of cardiovascular diseases has led to an escalating demand for cardiac bypass grafting (CABG), now recognized as the most prevalent cardiac surgical procedure

on a global scale. Despite autologous tissue interventions in CABG being considered among the most effective treatment options, their failure rate remains as high as 42.8%, with only 50% to 60% maintaining patency after a decade. Vascular engineering research has aimed to create tissue-engineered vascular grafts (TEVGs) in the

form of acellular or cellularized constructs as an alternative solution. Despite decades of research progress, only a limited number of TEVGs have progressed to clinical studies, and currently, there are no clinically approved TEVGs in use. Aim 1: Quantify VSMC infiltration in compliance matched TEVGs biofabricated with mesoscopic porosity

features in-vivo. First, we will test the hypothesis that the manufactured mesoscopic porosity features can influ- ence the rates of cellular migration and proliferation of native vascular tissue onto a tissue-engineered vascular graft (TEVG). In this Aim, we will employ two-photon subtractive manufacturing to enhance cell infiltration in our

compliance-matched TEVGs in vivo. This technology will create precisely cut pores to enhance cell infiltration.

The rationale behind this approach is rooted in the notion that heightened porosity will facilitate greater infiltration of vascular smooth muscle cells (VSMCs), thereby promoting enhanced engraftment and bolstering the produc- tion of extracellular matrix (ECM). By optimizing the porosity, we aim to create an environment conducive to robust

cellular integration and ECM synthesis within the TEVGs.Cellular migration and proliferation will be evaluated at the end of a 4 week time period. Aim 2: Quantify the hemocompatibility of SB coated compliance matched TEVGs in-vivo. Secondly, we will evaluate the efficacy of SB coating in reducing platelet deposition on our TEVGs in-vivo. We aim to investigate

whether SB-coated TEVGs will reduce platelet deposition on the graft surface and enhance in vivo hemody- namics. Additionally, we will conduct comprehensive characterization of the resulting polymers, examining their mechanical and thermal properties, hydrophilicity, biodegradability, and thrombogenicity. The rationale behind

this Aim lies in the hydrophilic nature of the SB coating, which is expected to mitigate thrombotic deposition both before and after significant degradation. This assessment aims to provide insights into the long-term performance and biocompatibility of the SB-coated TEVGs.