Bioprinting: Replacing Ink with Living Cells

by Manisha Kintali

Luke Massella was a ten-year-old boy suffering from the debilitating disease spina bifida under the care of Anthony Atala, M.D., in 2001. Born with this birth defect, Massella experienced numerous organ failures, including a paralyzed bladder, and could not enjoy a normal, active childhood. Ten years later, at the March 2011 TED Talk in Long Beach, California, the healthy college sophomore took center stage to commemorate and symbolize the achievements of his surgeon in the field of regenerative medicine. Atala’s work in the 3D printing of living tissue enabled him to create a new bladder, and a healthy future, for Massella through the innovative technology of bioprinting. Massella spoke with enthusiasm for the technology and for his own future, saying, “Because they used my own cells to build this bladder, it’s gonna be with me. I got it for life, so I'm all set.”

Bioprinting is the process of generating living tissue with the use of 3D printers, developing personalized organs specific to each patient. First, an MRI or CT image of the tissue is taken to determine the organ’s correct dimensions, which computer software then uses to create a blueprint. The blueprint indicates where the printer should place each type of cell during the printing process. Next, the cells from that tissue or organ are retrieved from the patient and are mixed with materials such as collagen to create a scaffold on which the cells grow. The mixture acts as printer ink, as the machine prints out the tissue layer by layer. During printing, hydrogel components give support and assist the cells in achieving their three-dimensionality. After completion, the tissue solidiﬁes with the help of UV light, heat, or certain chemicals to crosslink proteins. Lastly, the tissue sits in an incubator that maintains the same conditions of a human body, allowing the tissue to mature and exercise itself before use.

First introduced in the early 1980s by engineer Chuck Hull, 3D printing started as “stereolithography,” in which UV rays solidify light-reactive resin deposited layer by layer to create 3D parts. Over the past 30 years, the 3D printer has evolved and thrived in numerous fields by enthusiastic professionals. The results of 3D printing can be seen virtually anywhere, from automotive factories to toy stores, military bases to fashion runways.

Bioprinting has even presented an opportunity for the study of treatment for injuries sustained in the Syrian chemical warfare. As a precaution against chemical or biological attacks, the Department of Defense funded $24 million in 2013 to the “body on a chip” project led by Atala at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine. Atala and his team of researchers aim to reproduce a miniature model of human organs for observing harmful effects of toxins and testing the efficacy of drugs and antidotes. Bioprinting provides a more efficient method of scientific experimentation than alternatives such as animal testing, because of bioprinting's speed, cost-efficiency, and higher clinical applicability.

Bioprinting is currently at a stage where simple tissue and organs such as blood vessels and ears are being created. Biomedical engineers from Cornell University printed a functional external human ear made from a Jell-O-like mold consisting of living human cells and biosynthetic materials. The printed ear can be used for transplants, ideally for children born with ear deformities (young enough so that their auditory systems are still malleable enough to adapt to the new ears) or adults who’ve lost an ear due to accidents or medical injuries.

Complex organs such as hearts, kidneys, livers, and other highly vascularized organs are much more difficult to produce because they consist of different types of cells—achieving the same intricacy and full functionality in printed organs will take many more years. However, progress thus far points to its use in the arena of a major public health issue: organ transplantation.

According to United Network for Organ Sharing (UNOS), there are approximately 121,327 people on the transplantation waiting list today. As reported by the US Department of Health and Human Services, the waiting list grows every ten minutes, and 79 new patients are selected each day. In addition, 18 people from the list die daily from a lack of donor matches due to organ shortages.

Bioprinting can end this public health crisis by using printed organs for transplantation, serving as a viable alternative when a matching donor-recipient organ cannot be found. This innovation could alleviate the stress on the growing waiting lists and potentially save countless lives. Additionally, the patient’s own cells would make up the material of the organ, so the problem of matching and rejection from the immune system would no longer be an issue.

Organovo, a company based in San Diego, California, successfully printed a functional 3D human liver tissue model earlier this year. The tissue could be maintained under laboratory conditions for extended periods of time, allowing researchers to observe its actions when exposed to injury or study the effects of different kinds of treatments. This advancement gives hope to the proposal that printing a complete and viable liver is in the near future.

Research teams around the world are benefitting from bioprinting's innovations and inventiveness. Last year, Scottish researchers at Heriot-Watt University successfully printed human embryonic stem cells, creating millions of cells in a matter of minutes. Human embryonic stem cells are crucial to medical research because they have the ability to transform into any tissue type, and having the ability to produce these cells with printing provides a massive source for new research developments. Furthermore, cell survival after the bioprinting process now allows scientists to delve deeper into how these stem cells can be used to print different types of tissues or organs. In another interesting application from Malaysia, 3D printers create human brain models made entirely of biosynthetic materials to mimic the look and feel of an actual human brain and skull. These models are used by residents going through neurosurgical training to practice and perfect their techniques during different simulations without the pressure of causing any fatalities. At Pitt, 3D printed brain models using synthetic materials are used in research to improve MRI analysis.