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Researchers in Spain and the Netherlands have developed new hybrid bioinks that enable 3D bioprinting of artery models closely mimicking the layered structure and partial function of human blood vessels.
The team at CIC biomaGUNE, part of the Basque Research and Technology Alliance (BRTA), together with the University Medical Center Groningen (UMCG), the University of the Basque Country, and the MERLN Institute for Technology-inspired Regenerative Medicine, created these multifunctional bioinks by combining biological and synthetic materials to build multilayered cylinders resembling arterial walls.
Human arteries consist of three layers: the inner tunica intima, the middle tunica media, and the outer connective tunica adventitia. Reproducing this complex architecture in the lab remains challenging because each layer has distinct mechanical and biological properties, and most printed vessel models collapse or fail to mimic natural arterial behavior under pressure.
Published in Advanced Functional Materials, the study presents a method for producing stable, self-supporting cylindrical constructs through embedded 3D printing, where bioinks are extruded into a soft, transparent support bath that holds them in place during solidification. Using high-precision bioprinters such as the 3D Discovery from RegenHU and the BioScaffolder 3.1 from GeSiM, the team achieved precise alignment of concentric layers while preventing deformation.
Designing dual bioinks for arteries
The researchers created two complementary bioinks for the process. Called the “hybrid ink,” the first replicates the tunica adventitia, the outermost layer of the artery. It consists of an elastic, thermoresponsive polymer blend that includes gold nanorods capable of converting near-infrared light into heat. When illuminated, this outer layer contracts and expands in a controlled way, demonstrating a light-induced mechanical response rather than full arterial pulsation.
The second bioink represents the tunica media, the layer that contains vascular smooth muscle cells responsible for arterial contraction. To reproduce this structure, the team developed a material based on decellularized extracellular matrix (dECM) derived from porcine pulmonary arteries. After removing all cells, the remaining natural scaffold, rich in collagen and elastin, provided an authentic environment for human vascular smooth muscle cells to grow and spread.
The researchers enhanced this dECM with gelatin methacryloyl (GelMA), a derivative of collagen that solidifies under ultraviolet light. This combination improved both strength and biocompatibility. Proteomic analysis confirmed that the dECM preserved key structural proteins typically found in native arteries, including several types of collagen and fibrillin.
Once printed and crosslinked, the dual-layered cylinders maintained their structure without collapsing. Microscopy showed strong adhesion between layers, and live-cell imaging revealed that smooth muscle cells survived and expanded throughout the inner region for at least two weeks. When the constructs were exposed to pulsed near-infrared light, the gold nanorods generated rapid heating between 35°C and 38°C, producing reversible contraction and relaxation in the outer layer.
This light-driven response demonstrates that the hybrid bioinks can reproduce stimuli-responsive mechanical changes similar to mechanoadaptation, the process by which blood vessels adjust to physical stress. According to the authors, these models could be used to study how arteries respond to external mechanical and thermal cues without relying on animal tissues.
The technique also represents progress toward the fabrication of small-diameter vascular grafts for medical use, though further work is needed before these materials could be considered for implantation. The researchers plan to refine the mechanical balance of the inks and examine how cells sense and respond to the stiffness of their surroundings under dynamic conditions.
By combining inorganic nanomaterials with biologically compatible matrices, the team showed that it is possible to build complex and functional tissue models layer by layer. The resulting constructs reproduce the anatomy of arteries while also displaying active and tunable behavior under external stimulation.
This research highlights the potential of embedded 3D printing and hybrid bioinks to bridge engineering and biology. The approach could accelerate studies of cardiovascular disease, drug testing, and tissue regeneration by offering a reproducible and controllable alternative to human vessels.
Advances in vascular bioprinting
Advances in vascular bioprinting are enabling lab-grown tissues to function more like natural ones by creating personalized vascular networks and overcoming regenerative medicine’s key challenge of establishing a reliable blood supply.
Back in 2021, researchers at Texas A&M University’s Department of Biomedical Engineering developed a nanoengineered hydrogel bioink and used it to bioprint a multicellular blood vessel model. Designed for high printability and cell protection during extrusion-based bioprinting, the bioink incorporated endothelial and vascular smooth muscle cells to replicate the structural and functional characteristics of native vasculature.
It maintained cell viability and phenotype for nearly a month post-printing. The resulting model accurately recreated vascular microenvironments, offering a promising platform for studying cardiovascular diseases and testing drugs without relying on animal or human trials.
More recently, Penn State University (PSU) researchers developed a method combining 3D bioprinting with a surgical technique called micropuncture to promote controlled vascularization in damaged tissues. Supported by a $3 million National Institutes of Health (NIH) grant, the team led by Ibrahim Ozbolat and Dino Ravnic used 3D bioprinted biomaterial templates containing vascular channels to guide the direction and branching of new blood vessels.
Micropuncture, which involves creating tiny holes in existing vessels, triggered rapid sprouting that followed the printed pathways. Early animal studies showed successful vessel growth along the templates, offering promise for reconstructive surgery and tissue regeneration applications.
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Featured image shows multi-material embedded 3D bioprinting of concentric cylinders. Image via Advanced Functional Materials.
