Constructing Nitric Oxide‐Releasing and Reactive Oxygen Species‐Scavenging Hydrogels for 3D Printed Artificial Blood Vessels

Artificial blood vessel transplantation is considered the preferred surgical therapy for treating blocked blood vessels. Artificial blood vessels less than 6 mm frequently fail in vivo due to restenosis and thrombosis, significantly reducing the lifespan of the grafts. It is therefore crucial to develop antithrombotic materials for artificial blood vessels. This study presented a hydrogel with nitric oxide (NO) release, reactive oxygen species (ROS) scavenging, and antithrombotic properties, designed for eventual application in 3D printing artificial blood vessels. The hydrogel was primarily composed of double bond-modified recombinant collagen and hyaluronic acid (HA), along with caffeic acid arginine amide grafted onto HA, mimicking the protein/polysaccharide dual-network structure of the extracellular matrix. After modification, this hydrogel exhibited strong light-curing capabilities and shear-thinning qualities which were highly desirable for bioprinting. The hydrogel was capable of dynamically triggering and sustaining the release of NO, thereby effectively eliminating excess ROS at sites of inflammation. NO produced by the hydrogel enhanced the migration and proliferation of human umbilical vein endothelial cells while significantly inhibiting the proliferation of vascular smooth muscle cells. In terms of angiogenesis, the hydrogel demonstrated a significant ability to promote neovascularization. Furthermore, experimental results showed that platelet adhesion was virtually undetectable on the material surface, and protein adhesion was inhibited, thus minimizing the risk of thrombosis. Overall, this hydrogel bio-ink shows great potential for the 3D printing of small-diameter vascular scaffolds, offering a novel solution to address the issues of thrombosis and restenosis in artificial blood vessels.