Placing 3D-printed tissue in a custom bioreactor could help biomedical engineers build solid organs.
Thousands of patients are waiting for organ transplants because there are a limited number of donors. Engineered organs could help fill the gap. Yet despite decades of research, the only engineered internal organ that's been successfully transplanted into a person is a bladder, a hollow organ made from a thin sheet of tissue.
At the University of Texas, San Antonio, Teja Guda wants to build more complex solid organs that surgeons could transplant. To do that, he and his students are studying how to combine nerves, tissue and blood vessels to build a salivary gland and a tooth. An engineered salivary gland could eventually help people who have dry mouth syndrome. Guda plans to apply the lessons learned in producing this gland to building a pancreas because both glands have similar structures from an engineering perspective.
Eventually, Guda hopes to build any organ on demand by combining a standard set of building blocks for nerves, tissue, and blood vessels. But first his team needs to learn how these various components behave when combined in the same piece of engineered tissue.
Biomedical engineers have built simple structures such as blood vessels in the lab because that’s all they can do now. It is easy to keep thin tissues of cells alive by perfusing the thin tissue nutrients and oxygen, which then diffuse a short distance into its cells. But thicker organs need blood vessels to supply their internal reaches, and creating blood vessels to perform this function has so far been a nonstarter.
To place blood vessels in a block of tissue, Guda and his students start with a specialized 3D bioprinter that operates at low temperatures and pressures to keep from killing cells. They use it to create porous silk-based structures containing stem cells and fragments of blood vessels, both derived from fat. The pores between them help nutrients and oxygen reach all the cells.
Next, the researchers place the printed tissue in a custom plastic bioreactor that delivers physical cues that prompt the stem cells to develop in specific ways. The researchers design and 3D-print the bioreactor to fit the desired shape of a printed tissue, and to deliver fluid, electrical signals, or physical pressure to specific locations in the tissue.
The bioreactor for a tooth, for example, takes its shape from medical images of the jaw of a live cow. It could have two paths for fluid flow, each stream delivering different chemical cues and fluid pressure to the inside and outside of the tooth.
Biologists have learned a lot about the chemical and physical cues that help thin sheets of tissue develop, Guda said. Yet he and his students have to re-investigate these cues now that they’re combining blood vessels and stem cells in the same tissue. Often, they run into confounding trade-offs. Electrical current, for example, promotes nerve cell development, but electricity leaking out of nerve channels damages surrounding tissue.
Ultimately, Guda would like to develop a standardized set of materials and techniques to make complex structures and tissues. This way, research groups would find it easier to incorporate developments pioneered by other teams into their own work. Ultimately, standardized approaches would make it easier to gain regulatory approval for engineered organs, which would ultimately give doctors a wider variety of options for treating patients.
In the future, Guda imagines 3D bioprinters in hospitals building new organs during a surgery. After a surgeon removes fat from a patient, biomedical engineers would harvest its stem cells and print the new organ in the operating room. Then, the surgeon would implant the new organ in the patient, letting the patient’s body serve as the ultimate bioreactor.
In many cases, he thinks only a portion of a printed organ could function well enough to help a patient’s body heal itself.
He also envisions hybrids combining patient and donor cells into a single implant. For example, rather than printing an entire pancreas for a diabetic patient, Guda believes an implantable structure made from patient’s own cells that contains transplanted insulin-producing cells from a donor could extend the survival time of the donor cells so that the patient would no longer need daily insulin shots.
“Little victories like that along the way allow the science to continue,” Guda says.
Melissae Fellet is a science writer based in Missoula, MT.