# Syndecan-4 Functionalization Reduces the Thrombogenicity of Engineered Vascular Biomaterials

## TL;DR

Adding syndecan-4 to vascular biomaterials reduces blood clotting and improves compatibility with blood, making them better for tissue repair.

## Contribution

Syndecan-4 functionalization is shown to reduce thrombogenicity and complement activation in engineered vascular biomaterials.

## Key findings

- Platelet activation was lower on PFC and PFC_SYN4 compared to collagen.
- PFC_SYN4 showed 31% and 44% fewer platelet adhesion compared to PFC and collagen.
- PFC_SYN4 had reduced complement activation and improved clotting times compared to other materials.

## Abstract

Blood–biomaterial compatibility is essential for tissue repair especially for endovascular biomaterials where small-diameter vessel patency and endothelium formation is crucial. To address this issue, a composite biomaterial termed PFC fabricated from poly (glycerol sebacate), silk fibroin, and collagen was used to determine if functionalization with syndecan-4 (SYN4) would reduce thrombogenesis through the action of heparan sulfate. The material termed, PFC_SYN4, has structure and composition similar to native arterial tissue and has been reported to facilitate the binding and differentiation of endothelial colony-forming cells (ECFCs). In this study, the hemocompatibility of PFC_SYN4 was evaluated and compared with non-functionalized PFC, electrospun collagen, ePTFE, and bovine pericardial patch (BPV). Ultrastructurally, platelets were less activated when cultured on PFC and PFC_SYN4 compared to collagen where extensive platelet degranulation was observed. Quantitatively, 31% and 44% fewer platelets adhered to PFC_SYN4 compared to non-functionalized PFC and collagen, respectively. Functionalization of PFC resulted in reduced levels of complement activation compared to PFC, collagen, and BPV. Whole blood clotting times indicated that PFC_SYN4 was less thrombogenic compared with PFC, collagen, and BPV. These results suggest that syndecan-4 functionalization of blood-contacting biomaterials provides a novel solution for generating a reduced thrombogenic surface.