By Samantha Black, Ph.D.

October 22, 2019 -- Using bioinks formulated from smooth muscle cells from a human aorta and endothelial cells from an umbilical vein, researchers built a biomimetic blood vessel using 3D printing techniques.

The researchers from South Korea and Hong Kong published the results of the study in Applied Physics Reviews on October 22. The report includes details of the triple-coaxial 3D printing technology they developed and analysis of unique architecture, physical strengths, and biological activity of engineered blood vessels.

Gao et al.

Cardiovascular disease is a leading cause of death globally and results in over one million vascular bypass/replacement surgeries annually in the United States alone. There is a growing need for vascular substitutes for clinical use in patients who do not qualify for autologous vessels. Synthetic vascular grafts have been generally unsuccessful and result in fragile reconstructions that are prone to blockage.

Tissue engineering has emerged as a promising technique to overcome previous challenges for the reconstruction of biomimetic multiple-layered tissue-engineered blood vessels (TEBVs). However, this process can be laborious and time-consuming. Several strategies such as polymer scaffolds, self-assembling cell-sheets, and hydrogel mold-casting have been tested with varying levels of success. 3D printing, in particular, the coaxial-extrusion technique, is capable of constructing tissue equivalents with extreme precision. This makes it a great candidate method for producing small-diameter blood vessel grafts.

In a previous report, the researchers developed a vascular-tissue-specific bioink composed of vascular-tissue-derived extracellular matrix (VdECM) and alginate that not only stimulated the cellular functions of endothelial cells by providing a tissue-specific microenvironment but also facilitated the fabrication of endothelialized tubes.

The researchers set out to produce a graft with two essential functions: confluent and quiescent endothelium offering nonthrombogenic interface to inhibit thrombosis, and contractile smooth muscle tissues that can withstand hemodynamic stress, exhibit physiological compliance, and adapt to local blood pressure changes. Moreover, they investigated the performance of pre-matured TEBVs in vivo using a proof-of-concept rat model.

"The artificial blood vessel is an essential tool to save patients suffering from cardiovascular disease," author Ge Gao said. "There are products in clinical use made from polymers, but they don't have living cells and vascular functions. We wanted to tissue-engineer a living, functional blood vessel graft."

The researchers fabricated the printed blood vessel, they used the sjafdskjlhansfdkjl to print multiple concentric layers using bioink on an alginate fiber network. Because this form of the tissue would be unsuitable for use, they tissues were matured using an in vitro remodeling process, which allowed the tissue to stabilize and gain strength. The team confirmed the biological and physical changes using immunofluorescence staining (maturation), scanning electron microscopy (elongation), α-SMA staining (for contractile strength), and a battery of strength tests. Despite all of these changes, the compartmentalization of endothelial and muscular cells was retained. The researchers determined that the matured blood vessels accurately mimicked natural blood vessel function.

The matured blood vessels were then tested in vivo with a proof-of-concept study using rats. The Prematured TEBVs were implanted as interposition grafts. The grafts were able to withstand blood pressure, absence of blood clotting, positive signs implying the initiation of host tissue integration.

The authors plan to continue to develop processes to increase the strength of the blood vessels closer to that of human arteries. They also plan to perform long-term evaluation of vascular grafts, observing what happens as they continue to develop in place and become real tissue in the implanted environment.


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