Artificial arteries and veins
Hydrogel vessels behave like real ones
Irina Konova, PCR.news
Vessels made using 3D bioprinting and seeded with human cells are capable of vasoconstriction when treated with phenylephrine (center) and vasodilation when treated with acetylcholine (right). The scale marker corresponds to 200 microns. Credit: Shrike Zhang.
To restore blood flow in cardiovascular diseases, bypass surgery is performed, which involves the transplantation of fragments of the patient's own veins or the use of synthetic vessels. Both options have disadvantages. Thus, when using autologous material, complications may occur both at the site of the vessel intake and at the transplantation site. Synthetic vessels have a relatively low permeability (especially vessels of small diameters) and a short service life. Vessels made with the help of three-dimensional bioprinting can become an alternative to traditional synthetic implants. Scientists from the USA have developed a method of three-dimensional bioprinting of tissues imitating veins and arteries, and tested the vessels obtained with its help in vitro and in vivo.
The key stage of printing tissues imitating human ones is the creation of cytocompatible biochernils that provide the finished product with properties similar to those of natural vessels. The authors of the new work took as a basis a durable hydrogel with a double mesh (DN-hydrogel). The precursor biochernil, consisting of sodium alginate and gelatin, was cross-linked with calcium chloride and microbial transglutaminase. The resulting DN-hydrogel had the necessary strength, and its mechanical properties could be adjusted within wide limits, varying the concentrations of the components.
Arteries and veins consist of three layers: external connective, middle smooth muscle and internal endothelial. Scientists have used different approaches for bioprinting vessels of arteries and veins to reproduce their structure and properties. Vessels imitating veins consisted of a hydrogel tube, the lumen of which was seeded with human endothelial cells of the umbilical vein, and the outer surface with smooth muscle cells of the umbilical vein. A two—layer seal was used to create the arteries: the inner layer was formed from a stronger hydrogel providing mechanical support, the outer one from a softer hydrogel with encapsulated smooth muscle cells. The internal prostration was also seeded with endothelial cells.
Scientists have confirmed the proliferation and normal functions of the cells that make up the artificial vessels. Products imitating veins had barrier properties, and arterial mimetics were capable of vasoconstriction and vasodilation in response to appropriate stimuli.
Then the authors tested the vessels in vitro, ex vivo and in vivo. They suggested that the vessels obtained by bioprinting can be used as a three-dimensional model to study infections, for example, SARS-CoV-2 infections. Smooth muscle cells in the artificial vein actively expressed ACE2. The vein was infected with a pseudovirus carrying the coronavirus S-protein in the presence of antiviral drugs and without them. The drugs reduced the cytopathic effect of the virus and the number of infected cells.
In ex vivo experiments, artificial vessels were connected to explanted mouse or human vessels and fluorescent beads were passed through the system. Nothing hindered the movement of the balls, the system did not leak. Then, as a proof of concept, scientists implanted an artificial vein in place of the excised fragment of the vena cava of a live mouse. After removing the clamps from the vein, normal blood flow was restored in the mouse body.
Scientists plan to improve the technology, bringing the orientation of smooth muscle cells closer to the natural one. They note that further comprehensive studies of vessels obtained using 3D bioprinting, in vivo, are needed.
Article by Wang et al. Microfluidic bioprinting of tough hydrogel-based vascular conduits for functional blood vessels is published in the journal Science Advances.
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