Organs Without a Home: The Fascinating World of 3-D Bioprinting

his past February, the Wakeforest Institute of Regenerative Medicine accomplished the most advanced feat of tissue regeneration to date: they created a human ear, and kept it alive attached to the backside of a mouse. The ear, exhibiting human-like vasculature and cartilage development, is a promising beginning to the quest to create customized organs.

In creating tailored organs, ready upon request, the possibilities for eliminating diseases due to dysfunctional organs are endless. In the near future, the wait lists for kidney, liver, and heart transplants, among others, will no longer be dependent on the number of healthy donors, but on the time it takes printing factories to produce a customized organ. The reality of custom organs is well on its way -- and at its foundation is 3-D bioprinting.

The Technology

Bioprinting has evolved, over forty years, from modified inkjet printers that spurted out DNA fragments, to printing actual cells in a 3-D structure. In modern bioprinting, the machine prints cells in the form of the desired tissue or organ. As this technology evolves, certain obstacles arise. In particular, there are three notable issues in bioprinting that are being researched at present: scaffolding, the type of cells, and the inclusion of vasculature.

The bioprinter prints a scaffold of biomaterial compatible with cells and then continues to lay cells along the scaffold to create a functional tissue or organ. Researchers at the Wakeforest Institute of Regenerative Medicine have created a printer that prints the scaffold and cells simultaneously. This printer uses information collected through CT scans or MRIs to design the desired shape of the scaffold. Until now, the scaffold has been an important element of bioprinted organs because it gives the cells a stable surface to adhere to as they grow to form the organ in the shape dictated by this scaffold.

Next Steps

According to Gabor Forgacs, co-founder of the major tissue engineering company Organovo in San Diego, California, the bio-printed scaffold may be the next obstacle between designing functional tissues, and implanting functional organs. Forgacs experiments with aggregates of different types of cells to see if they will form more complex structures. "The cells know what to do because they've been doing this for millions of years. They learned the rules of the game during evolution," says Forgacs upon proving that cellular aggregates can function similarly to cells during embryonic development.

The "ink" in the bioprinter may also be altered, depending on the desired type of tissue or organ, such as cartilage, bone, epithelial tissues, and, most recently, embryonic stem cells. In 2013, researchers at the University of Edinburgh successfully bioprinted embryonic stem cells, opening up a new chapter of tissue regeneration. By 2015, scientists from Tsinghua University in Beijing and Drexel University in Philadelphia, developed a technique to grow embryonic stem cell units. These units, or embryoids, may one day be used as biological Lego blocks to assemble complex organs complete with the vasculature necessary for the organs to thrive and stay alive.

Developing the complete vasculature necessary for organ survival is the next big step in bioprinting. Creating blood vessels to transport oxygen and nutrients to the cells of a printed organ is already underway at the tissue engineering company Organovo. The necessity of this molecular transportation system is imperative for the organ's life: without it, the cells will simply die. Organovo is using a hydrogel, the same material used for contact lenses, to help fuse cells together in a tube structure. Once the cells fuse, the hydrogel scaffold is washed away and, just like that, a blood vessel is created.

However, researchers at the Wakeforest Institute of Regenerative Medicine have overcome the vasculature dilemma by printing mini tubules of hydrogel in between cells. The mini hydrogel tubules then act like synthetic blood vessels. So, instead of using cells as the material for the vessels, the scaffold is transformed into a transportation system, as well as a foundational structure. This technology played an important role in the Institute's breakthrough with the successfully implanted ear in February.

While We Wait

Despite the work of companies like Organovo, and Wakeforest's researchers, bioprinting has a substantial journey until organs can be designed and ready for human implantation. However, bioprinting provides a vast array of other opportunities. A perfect example is the lab grown human tissues that may be used to test subjects for drug development. Companies, including Organovo, are creating a market for synthesized specialized tissues, like liver tissues, which can be sold to pharmaceutical companies and researchers for testing. This method of testing propels the drug-discovery process right into clinical trials, and may bypass the need for animal trials.

Future uses of bioprinting are truly endless, ranging from tissue therapy in diabetes, to printing new skin directly onto burn patients, and even to giving medical students a real organ for surgical training. These techniques are expected to become common practice in the next few decades. Yet, inevitably, this new technology will provoke a plethora of economical and ethical questions.

Unintended Consequences

With bioprinting expected to dramatically extend life expectancy, what will be the possible consequences on global resources? The health care required to continue replacing organs, and the economic stamina required to fund extended pensions and to pay employees for longer, does not seem feasible.

Ethical challenges also arise. Bioprinting technology can also be easily manipulated to enhance the human life, rather than just to prolong it. All of our human faculties, including vision, hearing, and muscular strength, may be advanced past what is natural with technological intervention. These technologies will be expensive, and only available to the elite. Is it ethical, given the possible militaristic and political implications, to allow the creation of a superior subspecies of the human race?

Ethical dilemmas surrounding bioprinting may seem to be a matter of the distant future, but the issues arising with 3-D printing of inanimate objects are already present. During the last week of July 2017, the Transportation Security Administration discovered 68 3-D printed guns in carry-on bags across the United States. Although the viability of these weapons is debatable, the use of 3-D printing is already creating security issues.

Answers to these questions are vital to our medical, economic, and political future. In the mean time, such concerns should not detract from the healing promise seen in the regenerative medicine. Dr. Wadsworth, from the tissue regenerative company Aspect Biosystems, points out that patients, and their families, on waiting lists will be reluctant to voice these broader concerns: "The families of patients in this situation will see what we're doing in a positive light." As long as the technology is controlled, the rest of the world should see the bright side too.

By: Dana Lowry, Queen's University, September 2016.

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