On average, 18 people die each day while on the U.S. national waiting list for organ transplants. The demand for organs is so high – and the supply so low – that for many the wait for a transplant is too long. And then time runs out.
But what if there was another way? What if preserving a life didn’t have to hinge on another life ending? What if, instead, we could grow tailored-made tissues and organs in the 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 one. Eventually, livers, kidneys and hearts damaged by disease could be replaced with artificial organs. Such a scenario would reduce time and costs for patients, decrease the chances of rejection in some transplants and allow patients to sidestep many of the other hazards associated with 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,” said Ali Khademhosseini, a 36-year bioengineer who joined The University of Texas at Austin's Department of Biomedical Engineering as a Donald D. Harrington Fellow and visiting scholar for the fall 2011 semester. “So it would be a great biomedical use if we could treat those patients with artificial tissues and organs.”
In the not so distant past, this notion was unimaginable. But recent breakthroughs in the emerging field of tissue engineering are redrawing the boundaries of what’s possible in biology and engineering. Among its feats, the field has enabled the development of edible and artificially engineered meat, and – on the more serious side – tissue-engineered skin is aiding patients with severe burns and ulcers. This still up-and-coming field has also made great leaps toward making artificial organs a more conceivable and, potentially, viable option for treating patients in the future.
For that, 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 in the area of biomedical microdevices and biomaterials. He received his Ph.D. in bioengineering from the Massachusetts Institute of Technology (MIT), where he worked alongside the father of tissue engineering, MIT Professor Robert Langer.
Since then, his accolades have stacked. He was named in 2007 by Technology Review magazine as one of the top young innovators under the age of 35 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 early stages of their research careers.
Now, thanks to the Donald D. Harrington Fellows Program, Khademhosseini will temporarily trade 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 of Engineering’s Biomedical Engineering Department.
The fellows’ program that brought him here was created by Sybil B. Harrington as a tribute to her late husband. It is one of the most well 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 said. “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 working to forge 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,” said Nicholas A. Peppas, chair of the Cockrell School’s Biomedical Engineering Department. “He is one of the most imaginative and innovative young biomaterials and biomedical scientists and his contributions will have major impact in medical research.”
In many ways, they already are. Khademhosseini’s “living legos” research has helped change the traditional thinking around tissue engineering, and its 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 tissues – such as growing new skin tissue for burn victims – but it’s less effective at repairing the larger, more complicated tissues that make up the heart and liver. These tissues contain blood vessels, and they typically die or are 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 still 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 – most thrive.
“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. The reason for that is that cells are very smart and have all of the capability to make tissue, but they lack proper communication,” Khademhosseini said. “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" and uses tissue building blocks from specialized cells that are stacked, shaped and manipulated to form an organ.
With the technology, cells can be extracted from a patient’s body and then encased in a gel-like material developed by Khademhosseini. The material, which is 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.
Khademhosseini said that by giving cells in the organ the same environment and connections they have in the body, 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, to build a functioning organ.
“Pieces of organs are easier to make,” Khademhosseini said. “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.”
Working toward a common goal
Thanks to Khademhosseini’s unique research developments, scientists are getting closer. Still, he is quick to say, solving a challenge as complex as building artificial organs requires collaborative work between engineers, biologists and clinical doctors
“Everyone doing research in this area is focused on making an impact in the end,” Khademhosseini said. “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.”
