Thursday, December 12, 2013

Bioprinting the Heart in Decade




Actually it is surprising just how far along this all is.  Some pretty significant milestones have been reached to the point it may well be down to biochemistry.   This is something we can be pleased about.  Expanding budgets can well deliver us real success in a decade and this is extraordinary news.

It means of course that simple heart replacement becomes a viable option in the face of a failing circulatory system.  It also means that vein and artery replacement will become an important protocol.

Of course none of this actually extends ones biological lifespan but it makes it plausible that one can actually reach it.  All this technology is arriving rather quickly and I expect that the following two decades will allow total replacement of all tissues including parts of the brain.  Thus by 2035, it will be possible to sustain oneself in one’s prime to the end of biological lifespan.

I do then anticipate that we will have also long since learned how to reverse cellular aging itself to allow for very long lifespans.  Thus as humanity actually reaches its peak population our lifespans will extend that population into the centuries ahead. We have plenty of work to do anyway.

Bioengineer: the heart is one of the easiest organs to bioprint, we'll do it in a decade

21 NOVEMBER 13  by LIAT CLARK

A team of cardiovascular scientists has announced it will be able to 3D print a whole heart from the recipients' own cells within a decade.

"America put a man on the Moon in less than a decade. I said a full decade to provide some wiggle room," Stuart K Williams told Wired.co.uk.

Williams is heading up the hugely ambitious project as executive and scientific director of the Cardiovascular Innovation Institute at the University of Louisville. Throughout his prestigious career spanning four decades he has focused on researching surgical devices and bioengineering, and the idea for printing the heart whole from scratch was inspired by the work of one of the pioneers in both these fields -- Charles Lindbergh. Lindbergh might be best known for flying solo across the Atlantic and for the Crime of the Century (when his infant son was kidnapped and murdered) but he also created a glass perfusion pump with Alexia Carrel that would keep the human heart alive outside the body, paving the way for heart surgery. The pair also discussed regenerative medicine in their book The Culture of Organs.

"For bioprinting it is the end of the beginning as bioprinted structures are now under intense study by biologists"

Some 70 plus years after the publication of that book, Williams' predictions shouldn't sound all that incredulous, but he admits it's been met with resistance. "That's why we are excited," he tells Wired.co.uk. "Funding is very limited as this is a new area. But as bioprinting successes occur the interest will increase and then funding -- so many breakthroughs have occurred in this way with a new untested idea that is moved forward with limited resources.

"For bioprinting it is the end of the beginning as bioprinted structures are now under intense study by biologists."

Williams says he and his team of more than 20 have already bioengineered a coronary artery and printed the smallest blood vessels in the heart used in microcirculation. "These studies have reached the advanced preclinical stage showing printed blood vessels will reconnect with the recipient tissue creating new blood flow in the printed tissue."

The team has also worked on other methods of bioengineering tissue, including electrospinning for the creation of large blood vessel scaffolds that can then be joined with bioprinted microvessels.

But why print the parts, when you can print the whole in one go? We shouldn't just be able to repair the heart using bioengineering, but replace it.

The Cardiovascular Innovation Institute is now developing bespoke 3D printers for the job with a team of engineers and vascular biologists -- "if you do not understand the biology, you solve only half the problem" explains Williams. Though for now those printers are focusing on replicating the parts, the plan is to print the whole in one go in just three hours, with a further week needed for it to mature outside of the body. Certain parts will need to be printed and assembled beforehand, including the valves and the biggest blood vessels. "Final construction will then be achieved by bioprinting and strategic placement of the valves and big vessels," says Williams, who asserts that they are "on schedule" to build the bioficial heart within the decade marker. The bioprinter he says will be capable of achieving all the forementioned work, is under construction now in Louisville.

"Dare I say the heart is one of the easiest to bioprint? It's just a pump with tubes you need to connect"

Giving a simplified breakdown of the process, he explains: "a patient enters the operating room and tissue is removed (we think fat is the best source) and regenerative cells isolated. The cells are then mixed with solutions that contain extracellular matrix molecules and other factors and placed in the bioprinter. The bioprinter then prints the heart."

Bioengineers have already 3D printed a tiny functioning liver, but the problem is keeping it alive. The liver, for instance, was just a millimetre thick and four millimetres wide, and survived only five days.

The key to Williams' heart surviving could be in encouraging the natural self-organising of cells in that heart, that drives a process called inosculation he describes as the "knitting together" of cells. It's how surgeons explain the connection made between skin grafts and tissue. "The bioprinted vessels [will] inosculate with the recipient blood vessels, and blood flows into the printed vessels," says Williams. This is how those various parts of the whole will stitch together, with microvessels connecting the parts of the whole to get the nutrients where they need to be.

Kevin Shakesheff, director of the Wolfson Centre for Stem Cells, Tissue Engineering and Modelling and the UK Regenerative Medicine Platform Hub in Acellular Technologies, is in agreement that these final stages of the process will be integral to the group's success. "The foundations of the project are solid but there needs to be rapid progress in printing of such a complex tissues, in creating enough cells to print and in the maturation of the final tissue -- the fine connections between cells that make a heart functional." Nevertheless, Shakesheff told Wired.co.uk he does believe that a printed heart in ten years is possible. 

Compared to something like the liver, which relies on complex cellular processes for filtration, Williams believes starting with 3D printing a whole heart is actually a bit of a no-brainer. "Dare I say the heart is one of the easiest to bioprint? It's just a pump with tubes you need to connect. A kidney is much more complex.  And then the brain…" 

He is confident that the increased interest in the field will naturally support projects such as these as the field expands -- not least because of all the related technologies that will offshoot from the research. And this is what will keep them on schedule. 

"There is great interest and support [because] everyone understands this technology will lead to ancillary discoveries and new therapies to treat just part of the heart or part of the circulatory system." Of course, he admits, the early versions will be expensive -- something flagged up by skeptics of the technology. But that's the same for any groundbreaking technology.

"The big issue is money," Shakesheff tells Wired.co.uk. "To do this in ten years needs a massive amount of funding and the money needs to be spent properly and quickly."

We've already seen the cost of consumer-ready 3D printers plummet, and with the infinite possibilities provided by a biological 3D printer, it's only a matter of time before the latter follows suit.

One day, the bioprinter might be as ubiquiotus in hospitals as an X-ray machine.
Update: This article was amended on 22 November to include additional comment from professor Kevin Shakesheff.


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