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3D-bioprinted blood vessels are a major step towards man-made tissues and organs

One of the biggest challenges in building artificial organs is creating the vasculature. One successful way to construct artificial blood vessels is to 3D print sugar substrates, coat the outsides with cells, and then dissolve the sugar inside. An alternative approach now under development by Ali Khademhosseini and his colleagues, is to first print agarose (polysaccharide) tubes, embed them inside a hydrogel, and then seed the channels with blood cell precursors. Their latest results, published in the journal Lab on a Chip, suggest that vascularized printed organs may be within reach.

 

All the major organs are variations on a basic plan that consists of three elements: the arterial supply of blood into the organ, the venous drainage out, and a third tubular element that defines the primary function of the organ. For the kidney, this third actor would be the channels that collect urine. For the liver, it is the bile ducts. For the brain — depending on the particular vantage point taken — the synthesized product might be considered to be anything from the cerebral spinal fluid which circulates about it to consciousness itself.

These systems are not just incidentals of the organ, they are the organ. Therefore, getting the mechanics of the organ right means getting the vasculature right. The approach taken by Khademhosseini combines 3D bioprinting with a template micromolding process, and then uses photocrosslinking of various biogels to bond the whole works together. Unfortunately not a soul in the entire science media (including us) can divine the exact sequence of steps used here as it appears nobody has been able to breach the towering paywall of the paper. As far as the common man or woman is concerned, they might as well publish the stuff in the journal “Lab on Mars.”

For inspiration in this void, we might take a closer look at how real blood vessels are built by the body. The preferred way to do it, is for a close-knit group of cells to form a lumen within their midst. Basically this is a simple hollow space containing only fluid. How do cells create that? Well, it seems to be lumens all the way down. In other words, an individual cell first forms its own lumen within itself from various intracellular vacuoles. Through some topological membrane wizardry, these intracellular lumens coalesce and become a contiguous extracellular space, noentheless entirely within the cell assembly. Any cells caught on the inside then become the primordial blood cells.

 

Every organ, indeed every species, has its own version of these events, each influenced by the unique chemical function of the organ. A good physiologist can probably tell exactly what kind of environment an organism operates in just by looking at the relative lengths of the various loops and tubules of a kidney. For example, the demands of living in salt water are much different from those of a freshwater, both vastly different again from those of living in air. The geometry of the associated vasculature is eminently adaptable once the proper groundwork is laid, but getting things right in the beginning is the critical part.

For now researchers are just hoping to get stable structures that hold up to fluid pumped through them at physiologically realistic pressures. In the body this generally means replenishing weak parts of the fort with new recruits from locally-stashed stem cell populations. Much remains to getting everything right in an in-vitro scenario, but if we are to one day have fantastic totally artificial organs built from scratch, then those organs will need to be vascularized.

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