Skip to main content

collagen

3D Printing a Human Heart Valve

Posted on by

It is now possible to pull up the design of a guitar on a computer screen and print out its parts on a 3D printer equipped with special metal or plastic “inks.” The same technological ingenuity is also now being applied with bioinks—printable gels containing supportive biomaterials and/or cells—to print out tissue, bone, blood vessels, and, even perhaps one day, viable organs.

While there’s a long way to go until then, a team of researchers has reached an important milestone in bioprinting collagen and other extracellular matrix proteins that undergird every tissue and organ in the body. The researchers have become so adept at it that they now can print biomaterials that mimic the structural, mechanical, and biological properties of real human tissues.

Take a look at the video. It shows a life-size human heart valve that’s been printed with their improved collagen bioink. As fluid passes through the aortic valve in a lab test, its three leaf-like flaps open and close like the real thing. All the while, the soft, flexible valve withstands the intense fluid pressure, which mimics that of blood flowing in and out of a beating heart.

The researchers, led by NIH grantee Adam Feinberg, Carnegie Mellon University, Pittsburgh, PA, did it with their latest version of a 3D bioprinting technique featured on the blog a few years ago. It’s called: Freeform Reversible Embedding of Suspended Hydrogels v.2.0. Or, just FRESH v2.0.

The FRESH system uses a bioink that consists of collagen (or other soft biomaterials) embedded in a thick slurry of gelatin microparticles and water. While a number of technical improvements have been made to FRESH v. 2.0, the big one was getting better at bioprinting collagen.

The secret is to dissolve the collagen bioink in an acid solution. When extruded into a neutral support bath, the change in pH drives the rapid assembly of collagen. The ability to extrude miniscule amounts and move the needle anywhere in 3D space enables them to produce amazingly complex, high-resolution structures, layer by layer. The porous microstructure of the printed collagen also helps for incorporating human cells. When printing is complete, the support bath easily melts away by heating to body temperature.

As described in Science, in addition to the working heart valve, the researchers have printed a small model of a heart ventricle. By combining collagen with cardiac muscle cells, they found they could actually control the organization of muscle tissue within the model heart chamber. The 3D-printed ventricles also showed synchronized muscle contractions, just like you’d expect in a living, beating human heart!

That’s not all. Using MRI images of an adult human heart as a template, the researchers created a complete organ structure including internal valves, large veins, and arteries. Based on the vessels they could see in the MRI, they printed even tinier microvessels and showed that the structure could support blood-like fluid flow.

While the researchers have focused the potential of FRESH v.2.0 printing on a human heart, in principle the technology could be used for many other organ systems. But there are still many challenges to overcome. A major one is the need to generate and incorporate billions of human cells, as would be needed to produce a transplantable human heart or other organ.

Feinberg reports more immediate applications of the technology on the horizon, however. His team is working to apply FRESH v.2.0 for producing child-sized replacement tracheas and precisely printed scaffolds for healing wounded muscle tissue.

Meanwhile, the Feinberg lab generously shares its designs with the scientific community via the NIH 3D Print Exchange. This innovative program is helping to bring more 3D scientific models online and advance the field of bioprinting. So we can expect to read about many more exciting milestones like this one from the Feinberg lab.

Reference:

[1] 3D bioprinting of collagen to rebuild components of the human heart. Lee A, Hudson AR, Shiwarski DJ, Tashman JW, Hinton TJ, Yerneni S, Bliley JM, Campbell PG, Feinberg AW. Science. 2019 Aug 2;365(6452):482-487.

Links:

Tissue Engineering and Regenerative Medicine (National Institute of Biomedical Imaging and Bioengineering/NIH)

Regenerative Biomaterials and Therapeutics Group (Carnegie Mellon University, Pittsburgh, PA)

FluidForm (Acton, MA)

3D Bioprinting Open Source Workshops (Carnegie Mellon)

Video: Adam Feinberg on Tissue Engineering to Treat Human Disease (YouTube)

NIH 3D Print Exchange

NIH Support: National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Common Fund


Snapshots of Life: An Elegant Design

Posted on by

Collegen

Credit: David Sleboda and Thomas Roberts, Brown University, Providence, RI

Over the past few years, my blog has highlighted winners from the annual BioArt contest sponsored by the Federation of American Societies for Experimental Biology (FASEB). So, let’s keep a good thing going with one of the amazing scientific images that captured top honors in FASEB’s latest competition: a scanning electron micrograph of the hamstring muscle of a bullfrog.

That’s right, a bullfrog, For decades, researchers have used the American bullfrog, Rana catesbeiana, as a model for studying the physiology and biomechanics of skeletal muscles. My own early work with electron microscopy, as a student at Yale in the 1970s, was devoted to producing images from this very tissue. Thanks to its disproportionately large skeletal muscles, this common amphibian has played a critical role in helping to build the knowledge base for understanding how these muscles work in other organisms, including humans.

Revealed in this picture is the intricate matrix of connective tissue that holds together the frog’s hamstring muscle, with the muscle fibers themselves having been digested away with chemicals. And running diagonally, from lower left to upper right, you can see a band of fibrils made up of a key structural protein called collagen.


Cool Videos: Spying on Cancer Cell Invasion

Posted on by

Spying on Cancer Cell Invation

If you’re a fan of the Mission: Impossible spy thrillers, you might think that secret agent Ethan Hunt has done it all. But here’s a potentially life-saving mission that his force has yet to undertake: spying on cancer cells. Never fear—some scientific sleuths already have!

So, have a look at this bio-action flick recently featured in the American Society for Cell Biology’s 2015 Celldance video series. Without giving too much of the plot away, let me just say that it involves cancer cells escaping from a breast tumor and spreading, or metastasizing, to other parts of the body. Along the way, those dastardly cancer cells take advantage of collagen fibers to make a tight-rope getaway and recruit key immune cells, called macrophages, to serve as double agents to aid and abet their diabolical spread.


Building a Better Scaffold for 3D Bioprinting

Posted on by

A bioprinted coronary artery

Caption: A bioprinted coronary artery.
Credit: Carnegie Mellon University

When the heart or another part of the body fails, a transplant is sometimes the only option. Still, the demand for donated organs far outpaces supply, with thousands of people on waiting lists. Furthermore, transplants currently require long term immunosuppression to prevent rejection. Wouldn’t it be even better to create the needed body part from the individual’s own cells? While it may sound too good to be true, research is moving us closer to the day when it may be possible to use 3D printing technology to meet some of this demand, as well as address a variety of other biomedical challenges.

In a study published in the journal Science Advances [1], an NIH-funded team from Carnegie Mellon University, Pittsburgh, recently modified an off-the-shelf 3D printer to create gel-like scaffolds that could be seeded with living cells to produce coronary arteries, an embryonic heart, and a variety of other tissues and organs.These researchers, of course, aren’t the only ones making progress in the rapidly emerging field of bioprinting. Using more costly, highly specialized 3D printing systems, other groups have crafted customized joints, bones, and splints out of hard, synthetic materials [2], as well as produced tissues and miniature organs by printing and layering sheets of human cells [3]. What distinguishes the new approach is its more affordable printer; its open-source software; and, perhaps most importantly, its ability to print soft, biological scaffolds that set the stage for the creation of custom-made tissues and organs with unprecedented anatomical detail.