We can engineer artificial tissues to stand in for parts of the human body in scientific and medical research, and in clinical applications. These tissues contain a crucial system of blood and lymph vessels known as the vasculature. Fabricating an artificial vasculature presents major challenges to researchers, as it involves creating complex interconnected capillary networks and branching artery- or vein-like channels as small as 0.5mm in diameter.
The accurate construction of fabricated vasculature has become possible with the emergence of 3D bioprinting techniques. Ross Fitzsimmons of the Simmons lab at the University of Toronto in Canada explains how bioprinting revolutionises this task: “By determining the optimal methods and materials to generate vascular structures, engineered tissue constructs can be made larger and still remain viable, which is of critical importance for their use in clinical applications or in drug screening.”
To create vasculature, 3D bioprinters use the special properties of a ‘sacrificial material’. This is a substance that moulds the required vascular structures during printing, then flushes away to leave hollow channels. Researchers are still struggling to identify the optimum substance to perform this role, as it needs to fashion the desired vascular architecture accurately and consistently while remaining non-toxic.
Fitzsimmons and his colleagues assessed two leading candidates, gelatin and Poloxamer 407, and published their results in the Elsevier journal Bioprinting. Using an inexpensive open-source 3D bioprinter that they developed themselves, they found that both substances showed promise.
“Overall, of all formulations tested, Poloxamer 407 was found to print filaments with the highest spatial resolution and with low toxicity,” Fitzsimmons notes. “However, the printability of gelatin could approach that of Poloxamer 407 by increasing its viscosity with a hyaluronan additive.”
The research indicates that, depending on the exact characteristics needed from the fabricated tissue, gelatin-hyaluronan might be superior to Poloxamer 407. This might be the case, for example, if the sacrificial material needed to provide structural support during printing.
Fitzsimmons added that the bioprinter developed for the assessments could itself have a number of research applications. For this kind of research, bioprinters need to have the precision required to print all the channels of the tissue to be fabricated, and to be able to deposit at least two substances, namely the tissue and sacrificial materials. Such bioprinters can be prohibitively expensive for research labs.
Nevertheless, the bioprinter developed by Fitzsimmons and his colleagues cost less than CAD$3,000. “We designed it using 3D-printed and laser-cut components with off-the-shelf electronics and open-source software to allow for easy assembly by future adopters of the design,” he explains. The printer design files have now been made freely available online for other researchers to use.
“The development of an open-source 3D bioprinter that is inexpensive and yet still has the capacity to print multiple materials at high resolution, will enable a greater number of labs to produce complex tissues and help facilitate new biomedical discoveries,” Fitzsimmons concludes.
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Fitzsimmons, REB, et al.: "Generating vascular channels within hydrogel constructs using an economical open-source 3D bioprinter and thermoreversible gels,”Bioprinting (2018)