# Biomimetic bilayer hydrogel coating with antithrombotic and anticalcification properties for cardiovascular tissue engineering application

## TL;DR

A new hydrogel coating improves the durability and safety of cardiovascular tissue engineering scaffolds by mimicking the endothelium and preventing blood clotting and calcification.

## Contribution

A novel biomimetic bilayer hydrogel coating is developed to enhance the antithrombotic and anticalcification properties of tissue engineering scaffolds.

## Key findings

- The HCT hydrogel anchors into the ASB matrix, improving biostability and mechanical properties.
- The SilMA hydrogel enhances hydrophilicity and antifouling properties of the coating.
- The bilayer coating shows excellent anticoagulation, endothelialization, and calcification prevention in animal models.

## Abstract

Decellularized extracellular matrix (dECM), a promising tissue engineering scaffold for cardiovascular applications, might exhibit enhanced durability when endowed with anticalcification and antithrombotic properties. Herein, we present a biomimetic bilayer hydrogel coating applied to acellular swim bladders (ASBs). First, we designed an endothelium-mimicking (HCT) hydrogel coating, comprising alternately assembled endothelial glycocalyx macromolecule hyaluronic acid, copper ions, and tannic acid. Subsequently, a hydrophilic methacrylated silk fibroin (SilMA) hydrogel was incorporated as the outer coating layer. Notably, the HCT hydrogel penetrated and anchored into the ASB matrix, forming an interpenetrating network that enhanced the biostability and mechanical properties of the ASB matrix. Additionally, the SilMA hydrogel enhanced the hydrophilicity and antifouling properties of the HCT coating. In vitro experiments and subcutaneous implantation further revealed that the bilayer hydrogel (H/S) coating exhibited excellent biocompatibility, hemocompatibility, antibacterial activity, and anticalcification properties. Furthermore, a blood circulation model and rabbit shunt assay confirmed the great anticoagulation properties of the H/S coating. Moreover, in an in vivo rat carotid aorta replacement model, the H/S coating effectively promoted endothelialization, enhanced vascular remodeling, prevented calcification and thrombosis, and ultimately improved ASB durability. Based on these findings, our endothelium-mimicking hydrophilic bilayer hydrogel coating holds great promise as a surface modification strategy for tissue engineering scaffolds.