Feb 16 2016
A new study published recently in Nature Biotechnology reports a significant advance in the technology of 3D printing body parts designed to be implanted in human patients. This is an exciting technology, but we are still in the early phase of development.
Printing body parts is one approach to creating tissue and organs to replace those lost, damaged, or diseased. This is a top down approach, directly constructing the body part. The other approach is bottom up – growing a body part from stem cells.
The 3D printing technology itself is more than adequate for this task. That is in no way the limiting factor – we can create objects of precise size and shape sufficient for implantation. We can, for example, make an exact replacement for a missing piece of bone.
The biggest limiting factor in creating body parts of “clinically relevant size, shape, and structural integrity,” is keeping the cells alive. The problem is when we print body parts we are printing the skin, muscles, bone, and cartilage, but not nerves or blood vessels. Without blood vessels, the only way for the cells to get oxygen and nutrients is through direct diffusion, which has a limit of 100-200 micrometers. This is too small to be clinically useful.
This was the specific advance reported in the recent study. The researcher incorporated pores or microchannels into the printed tissue, allowing for far greater diffusion. The tissue became more like a sponge. The bottom line is that this technique worked, they were able to create cartilage, for example, of 3.2 cm x 1.6 cm x 0.9 cm which survived in vivo without necrosis.
There is more to this system, however, which they call “integrated tissue-organ printer” or ITOP. In addition to extending the diffusion limit, they improved the structural integrity of the printed body parts.
The printer uses a hydrogel infused with the desired cell type. The hydrogel supports and nourishes the cells while they grow. They also print with two supporting materials, an internal polymer (PCL) and a “sacrificial” or temporary external scaffolding. The scaffolding provides only temporary support.
The PCL, however, provides significant internal structural integrity (also important to maintain the pores) and degrades slowly, over 1.5-2 years. During this time the cells secrete their own protein matrix which replaces the PCL providing biological structural stability.
During this time nerves and blood vessels will also grow into the new tissue. The blood vessels will ultimately allow for oxygen and nutrients to penetrate the tissue, making the microchannels unnecessary.
In the study they printed bone parts and transplanted them into rats. The parts were retrieved five months later, and were viable at that time, showing mature vascularized bone.
The authors report that now they need to do longer term studies and they also need to study the response of the host immune system, to make sure there are no signs of rejection.
While all of this is exciting, at this point we are 5-10 years away from human trials – actually implanting 3D printed body parts like this into human patients as part of a study. Routine clinical use is therefore 15-20 years away, if all goes well.
There is also the issue of, for which specific applications will this technology work best? Printing external ear parts or pieces of jawbone seem to be the low-hanging fruit. But how far will the technology go? Can we eventually print hearts and livers? What about limbs?
Being able to replace any body part with a new and healthy part is the “holy grail” of regenerative medicine. 3D printing technology is advancing quickly, and seems to have great promise, but I suspect it will be most useful for only a subset of possible body part replacements.
The other alternative, growing body parts from stem cells, seems to have more ultimate potential. This technology is also likely decades away, especially for the more sophisticated applications. Simply implanting stem cells into existing structures (like injecting heart cells into the heart) can happen much sooner. Replacing entire organs, limbs, or other body parts is more tricky.
This approach requires coaxing stem cells to differentiate into not just one tissue type, but to develop into a mature body part. One of the greatest difficulties of this approach is getting the cells to do this outside of a fully developing fetus. Body parts grow as part of a whole, partly under control of chemical signals made by the environment of the growing fetus.
As has already been explored in science fiction, one way to achieve this is simply to grow a full person. Some writers have envisioned a future in which people (at least the rich) harvest cells while they are young to grow a clone which is kept as a source of spare body parts. We could get around the dicey ethics of this approach by growing a headless or at least brainless body, a meat bag of body parts. Keeping such a body alive for years or even decades until it is needed is likely an expensive and resource-intensive approach.
Growing isolated body parts on demand is a much better option, but that is the tricky technology we have yet to work out.
The advantage of growing body parts is that they can grow with nerves and blood vessels integrated from the beginning, including all the elements of structural integrity and functionality. Implantation would then be very much like transplanting a body part from a donor.
There are two huge advantages to growing rather than donating a body part. The first is that you don’t need a donor, which is a significant limiting factor. There are simply not enough donated organs to go around.
The second advantage is that, if the body part is grown from the patient’s own stem cells, then it will be an identical immune match, and there will be no risk of rejection or need for powerful immunosuppressive drugs.
One disadvantage is time. In order to grow an organ suitable for implantation into an adult it might take years.
There is another option, at least for some body parts – growing them as part of genetically modified animals. We could theoretically genetically modify a pig, for example, to have essentially a human immune system. We might even be able to give them the same immune systems as the eventual recipient. It is also theoretically possible to modify the animals so that the organs are more anatomically compatible for human transplantation.
With animals as donors, parts could be grown on demand. Pigs and other animals mature much more quickly than humans. It might take as much or less time than patients typically are on a transplant waiting list to simply grow them a donor organ inside a pig.
Ultimately I think we will have a system that uses all of these technologies, perhaps combined with others such as robotic prosthetics. Different technologies may be best suited for different applications. Robotic limbs, for example, may be the best option, while we grow humanized pig hearts, and 3D print precise bone sections to replace damaged parts.
We should develop all of these technologies simultaneously, because it is still too early to predict how they will each pan out, how long it will take, and to what applications they will be best suited.
4 Responses to “3D Printing Body Parts”
Leave a Reply
You must be logged in to post a comment.