Have a Heart

One of the hottest names in bioengineering, Ali Khademhosseini, has spent the fall at UT working on growing artificial organs. How is this possible?

On average, 18 people die each day while on the U.S. national waiting list for organ transplants. But what if there was another way? What if the preserving of one life didn’t hinge on the ending of another? What if, instead, we could grow tailor-made tissues and organs in a lab to replace those damaged in the body? In place of a heart transplant, heart-attack patients could receive lab-grown muscle tissue to replace their weakening organ. Eventually, livers, kidneys, and hearts damaged by disease could be replaced with artificial organs. Such a scenario would reduce the time and cost for patients, decrease the chances of rejection in some transplants, and allow patients to sidestep the hazards surrounding organ donation. Fewer transplants would be necessary. More people would live.

“There’s a huge shortage currently of transplant tissues and organs. For so many different diseases, there’s no current treatment and, for someone to get a transferable organ, someone potentially has to die,” says Ali Khademhosseini, a 36-year-old bioengineer who joined UT’s Department of Biomedical Engineering as a Donald D. Harrington Fellow and visiting scholar for the fall semester. “So it would be a great biomedical use if we could treat those patients with artificial tissues and organs.”

Until recently, this notion was unimaginable. But recent breakthroughs in the emerging field of tissue engineering are changing the boundaries of what’s possible in biology and engineering. Among its recent advances, the field has enabled the development of edible and artificially engineered meat, as well as tissue-engineered skin that aids patients with severe burns and ulcers.

When it comes to growing artificial organs, Khademhosseini is among an esteemed group of scientists at the forefront of innovation.

Despite his relatively short time in academia, Khademhosseini is internationally regarded for his research contributions to the area of biomedical microdevices and biomaterials. He received his PhD in bioengineering from the Massachusetts Institute of Technology, where he worked alongside the father of tissue engineering, professor Robert Langer.

Since then, his accolades have continued to stack up. In 2007, he was named one of the top young innovators under the age of 35 by Technology Review magazine for his landmark development of “living legos” (a novel tissue engineering technique that holds great promise for building artificial organs). Most recently, he was selected by the White House to receive the Presidential Early Career Award, the highest honor bestowed by the federal government on science and engineering professionals in the beginnings of their research careers.

Now Khademhosseini has temporarily traded his posts at Harvard Medical School, the Harvard-MIT Division of Health Sciences Technology, and Brigham & Women’s Hospital to spend a semester at the Cockrell School.

The fellowship that brought him here was created by Sybil B. Harrington as a tribute to her late husband. It is one of the best-endowed visiting scholar and graduate fellow programs in the nation and the most prestigious at the University. Only five fellows are selected annually, all of whom are considered the most exceptional young academics in their research fields.

“I wanted to come here because I knew I would get the chance to interact with faculty who are very accomplished in the engineering and scientific communities,” Khademhosseini says. “And the Biomedical Engineering department is already very strong in a lot of different areas that I’m interested in.”

While here, Khademhosseini is tapping into the University’s engineering expertise and forging research and funding opportunities that could extend from Austin to his lab in Boston.

“Ali is one of the brightest stars currently leading research in the bioengineering field,” says Nicholas Peppas, chair of the Cockrell School’s Biomedical Engineering department. “He is one of the most imaginative and innovative young biomedical scientists, and his contributions will have a major impact on medical research.”

In many ways, they already are. Khademhosseini’s “living legos” research has helped change traditional thinking around tissue engineering, and it is bringing researchers a step closer to the ultimate engineering challenge: to build an entire functioning organ.

A New Way of Thinking

Traditionally, tissue engineering has relied on a scaffold-based approach for repairing organs. The process uses naturally derived or synthetic materials that are fashioned into a biodegradable scaffold, or temporary structure, and then implanted along with cells into the transplant recipient’s body. Once inside, the cells within the scaffold form tissue as the structure slowly dissolves.

The method has been successful at repairing small pieces of tissue, like growing new skin tissue for burn victims, but it’s less effective at repairing the larger, more complicated tissue that makes up the heart and liver. This tissue contains blood vessels, and it typically dies or is rejected when transplanted with the scaffolding method because not enough oxygen can get into all of the cells that form the tissue.

A final hurdle is that different scaffolding structures are needed to build different types of tissues. Muscle tissue in the heart, for instance, is striated, while muscle tissue in the liver is hexagonally shaped. The ability to recreate these complicated tissue shapes is difficult and limited by scaffolding.

Khademhosseini’s “living legos” can overcome this. The method’s success comes from its ability to mimic the different types of environments in which cells—the very building blocks of tissue—thrive the most.

“Many people think you can just clump cells together and they become tissue, but nature has generated over 200 different cell types, and they interact with each other in very defined and different ways that are unique to each tissue,” Khademhosseini says. “The reason is that cells are very smart and have all of the capability to make tissue, but they lack proper communication. If we can engineer the environment, we can give them the right communications so that they reengineer and make complex tissues, and, one day, organs.”

Khademhosseini’s novel, modular approach to tissue engineering treats cells like living legos, using tissue building blocks from specialized cells that are stacked, shaped, and manipulated to form an organ.

With this technology, cells can be extracted from a patient’s body and then encased in a gel-like material developed by Khademhosseini. The material, which can be naturally or artificially derived and has a texture similar to Jell-O, mimics a cell’s natural environment. The material can also be molded into desired shapes, making it easier to design a striated muscle structure for the heart or a hexagonal structure for the liver. Once the material and cells are transplanted into the body, the cells stretch and form tissue while the material slowly dissolves. Each block of tissue is no wider than a strand of hair, so many blocks are stacked together into the shape of the desired tissue.

By giving cells in the organ the same environment and connections they have in the body, Khademhosseini says, scientists will be able to the grow larger, more complicated tissues that are needed for organs like the heart and liver. The tissues will prove critical for testing new drugs and, eventually, for building a functioning organ.

“Pieces of organs are easier to make,” he says. “But making an entire organ requires all of the pieces to work together, and that is much more difficult to do. Once we get better at building those individual pieces, then we can begin work on building a functional organ.”

Thanks to Khademhosseini’s unique research developments, scientists are getting closer. Still, he is quick to point out that solving a challenge as complex as building artificial organs requires collaborative work between engineers, biologists, and doctors.

“Everyone doing research in this area is focused on making an impact in the end,” Khademhosseini says. “It’s not like one person wins if he or she comes up with the therapy. If there is a successful therapy, then everyone wins.”

Photo by Sarah Lim.



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