Designation: Professor of Bioengineering, Chemical Engineering, and Radiology
at UCLA, USA
Work: Nano and Micro fabricated Hydrogels for Biomedical Applications
Field of the Prize: Life & Medical Science and Technology
Changing the World
Ali khademhosseini; An Intimate Profile
For a bioengineering researcher, no paradise could be imagined as more welcoming than a lab on the ‘bridge’ between a medical school and an engineering school in one of the most pioneering universities in the world. Just here, at this strategic bridge, lies Khademhosseini Lab at UCLA. “Our research really bridges the two and this is one of the things I’m very excited about,” says Ali Khademhosseini, the Levi Knight Professor of Bioengineering, Chemical Engineering and Radiology at the University of California-Los Angeles (UCLA).
Ali Khademhosseini was born on October 30, 1975, in Tehran. “I recall that my brother and I grew up in a loving family. Our parents always encouraged us to do well and be the best we can be. I think that both my parents have helped me in having the important values in life,” he says.
Then everything changed with the advent of the war between Iran and Iraq in 1980 when he was only five. “I remember vividly one time we were sitting down and there was a mushroom cloud that went up a few blocks from where we were that one of the rockets had hit it. So obviously it’s some experiences that you never forget but at the same time, it makes you appreciate the opportunities that you have in the US right now,” he says.
To offer a better future for Ali and his brother, his parents decided to move their family to Toronto, Canada, when he was 12. He liked playing video games and reading at home, as well as outdoor sports. Math and science was his favorite subject in school. At various times he wanted to have different careers like a professional athlete, chess player, high school teacher. Later on, however, when he went to university and found his passion for research he became interested in becoming a professor.
“I was always interested in seeing how the world works and the fundamental laws that govern it. I used to watch a lot of documentaries about nature, science, and technology. I think that despite this my passion did not really get ignited until I was in the third year of university and got my first research experience,” he says.
During the summer of his third year studying chemical engineering at the University of Toronto, he had the opportunity to get involved in undergraduate research in the area of biomaterials, under Dr. Michael Sefton. He found it fascinating to see the engineering knowledge that he had been studying at the university become useful in solving important medical problems.
After getting his Master’s at the University of Toronto (2001), he was accepted as a Ph.D. student at MIT. There he met and inspired by Dr. Robert Langer, one of the twelve Institute [= distinguished] Professors of MIT, and a world-renowned figures in biomedical engineering innovation. “Professor Robert Langer showed me that there are no boundaries in what an individual can achieve. He was really important in my professional development,” he says. “You see the humility and kindness of the person towards people he interacts with. It really does change your mind. It still motivates me, pushes me forward.” He received his Ph.D. in bioengineering from MIT in 2005, with Dr. Langer as his doctoral adviser.
The other mentor Khademhosseini recalls of having a great effect is Nicholas Peppas of the University of Texas at Austin who “has been very influential and helpful” and helped him to improve his “critical thinking and managing academic life.”
Khademhosseini was a professor at Harvard Medical School and a director at Biomaterials Innovation Research Center (BIRC), a leading initiative in constructing engineered biomedical materials. Then he joined the Division of Health Sciences and Technology, which is one of the largest academic collaboration between Harvard and MIT in the last half-century. From Nov. 2017 he joined UCLA and is the founding director of the Center for Minimally Invasive Therapeutics at UCLA.
Khademhosseini is trying to develop various types of diagnostic and therapeutic strategies by merging engineering and medicine. For example, his team develops ways of engineering artificial tissues using advances in stem cell biology, 3D printing, and materials science. “Our research can make great impact in medicine by making long-lasting therapeutics that can benefit the patient for many different types of diseases, ranging from cancer to trauma and organ failure due to old age,” he says. “Our work has the potential to change medical practice.”
He is an author in more than 600 scientific paper and book chapter which have been cited more than 55,000 times so far (75% of them in the last 5 years) and brought him an H-index of 123. Khademhosseini was selected by Thomson Reuters as one of The World’s Most Influential Minds and was a regular name in the Web of Science list of Highly Cited Researchers in the past few years. This list recognizes researchers producing publications that rank in the top 1% of the most cited. He is also on the editorial boards of many journals with high impact factor among them are ACS Nano, Small, Biofabrication, Lab on a Chip, and Biomacromolecules.
He is a recipient of more than 40 major national and international awards, including the 2011 Presidential Early Career Award for Scientists and Engineers (PECASE), and a fellow of many learned societies, both domestic and abroad, including American Association for the Advancement of Science (AAAS) and Royal Society of Chemistry (RSC).
Khademhosseini is a family man. “When I am at home I like to play games with my son and teach him things. I love spending time with my son! Also, I like to spend time with friends. My wife is also very supportive and we try to go out in the sun of Los Angeles or drive around California,” he says.
He likes to be known and recalled as a good mentor as well. “I really care for everyone who is in contact with me and try to make sure that they have a good life.” Many of his former students and postdoctoral fellows now work as successful researchers in the most prestigious universities in the world. This is why he received the title of MIT’s Outstanding Undergraduate mentor.
Many students interested to work with Khademhosseini, especially from Iran and other Middle Eastern countries, are rushing into his lab. “I always see myself as one of those people who could have been applying to my lab. My main advice to any student is that first to explore different things and find your passion,” he says. Khademhosseini believes that a researcher should believe that he or she is solving important things. “You’re not just doing something that keeps you busy like solving a puzzle that at the end no one cares about. If you actually do your work then you can make a big impact, you can change the world,” he thinks.
Printing Spare Life
Biofabrication may be a little bit off in the future, but it still seems the future of medicine
Biofabrication seems like a word embodied all the good dreams of both a transplant patient and a bioengineer. If your kidneys are failed, would you like two new ones to be printed for you? If there is no histocompatible lung available for your terminally sick patient, would you like to print a new pair for her using her own cells? Does it like an extreme case of science gone magic?
The tissues and organs of living things are the result of the genetically programed developmental processes that evolved for a long time. Now biofabrication seems an artificial alternative to make tissues and even whole organs: Life 2.0. And you need life 2.0 most urgently when the life 1.0 has failed – a sort of life after life.
The world population is going to age in the coming decades and it is estimated that the number of people aged 65 and older would be doubled by 2050 and constitute one-sixth of the whole population. Current treatments, such as joint replacement and organ transplantation, suffer from infections, tumor malignancies, immunosuppression necessity, and supply shortage. 3D constructs and other regenerative therapeutics provide a reliable option of minimally invasive surgeries to address their organs' natural deterioration.
Print or Perish
The basic principle is called additive manufacturing or printing a concoction of cells, fibers, and gel, layer on layer. Thus the 3D printing technology has a central role in biofabrication as a powerful tool to accurately put cells into a matrix.
Many tissues consist of several types of cells. So it is very desirable to print all of them together instead of using stem cells and waiting for them to differentiate. These printed tissues then are hoped to reorganize and remodel themselves to a fully matured and interconnected structure.
Currently the list of constructs, or things that can be printed using this bioink, is long and includes a range of tissues like skin, tendons, cartilage, bone, blood vessels, nervous, the pancreas islet cells, trachea, as well as whole organs such as kidneys, bladder, liver, lung, heart and more.
These tissues and organs can be used both for treatment and for research: They could be used as a substitute in the medically challenged and replace the damaged ones. And they could be used as a realistic model to test new drugs, and discovering the cellular biology mechanisms while reducing animal use in research.
Bones of Contention
The bioink using in the three-dimensional bioprinting is indeed a cell-laden biomaterial fed into the printer. For example, those used for bone bioprinting are hydrogels bearing cells, bioactive ceramics, and growth factors, which should be stable at normal body temperature. Hydrogels are indeed hydrophilic networks of polymers like collagen or polysaccharides that turn into a gel when hydrated (over 90% water). The hydrogels are basically like a natural tissue devoid of all its cells. To give them a rigid three-dimensional shape and mimic a natural tissue scaffold, researchers use cross-link nanofibers. And they act as a medium to manage cells by adding biosignaling molecules.
The most common hydrogel in bioprinting is alginate, or salts of alginic acid, which is a polysaccharide isolated from brown algae. Alginate forms a viscous porous gum when hydrated and is the most frequently used biomaterial due to its low cost and biocompatible nature. Another biomaterial that is being investigated as bioink is silk fibroin which is derived from both silkworm and spider silk.
What are printed by 3D technology are scaffolds that then could be seeded by the respective tissue cells. Now the 3D bioprinting takes a further step and use bioink containing cells and bioactive cues and have many advantages over ‘traditional’ two-step printing.
Bones are a most demanded tissue in transplant surgeries. They may defect because of many factors such as congenital abnormalities, trauma, disease, or surgical resection. Bone grafts to restore structure and function come usually from the same person’s body (autografts) or are donated by another person (allografts), and as they must be healthy, they should be considered as a limited resource. And synthetic biomaterials just will not do the work properly. After all, bones are complex living tissues with blood vessels and using this technology in clinical settings could be accompanied with complications not least among them the immune reaction or lacking the right mechanical properties or the potential to fuse in the recipient sites.
Off in the Future
Considering all these formidable challenges, it is not surprising that 3D printing is one of the cutting edges in the fast-advancing research area of regenerative medicine. Developing complex custom-made constructs for personalized regenerative treatment has recently ignited much research interest.
Much of what said above and many more are in the realm of Ali Khademhosseini, bioengineering professor and director of the Center for Minimally Invasive Therapeutics at the University of California-Los Angeles (UCLA). He, as a world-leading expert in tissue engineering, concedes that currently, the main use of bioprinting is in vitro - by reducing the number of failed drugs. This makes it possible to test different drugs on patient genetically unique tissues outside of his body before prescribing medicine for him.
Khademhosseini, the laureate of the 2019 Mustafa Prize for ‘nano- and microfabricated hydrogels for biomedical applications,’ accepts that much of being dreamed of in the field of bioprinting, especially in the form of transplantation by putting cells in a printed architecture and converting it to a living functioning tissue, is “still a little bit off in the future.” In the future, we should be able to custom-made tissues and organs for each person using his or her own genomic data.
These kinds of testing are now underway and the results are being fed to machine learning algorithms to improve predictiveness. The challenges are vast and various, however, “I’m sure with time we’ll be able to solve all of them,” said Khademhosseini in an interview with UCLA Samueli School of Engineering. A host of Middle-Easterner researchers currently are working on similar subjects in the most prestigious universities, such as UCLA and Harvard Medical School.
All of this bioprinting issue reminds many of the Westworld, a TV series based on a 1973 work written by Michael Crichton. The opener shows two 3D printers working simultaneously to extrude out of their nozzles the final touches of the skeletomuscular and vascular systems and finally skin of ultra-realistic robotic hosts of an amusement theme park along with their horses and guns. However, many academic labs throughout the world are busy researching and developing any aspect of this concept intensively. Many of those fictions will become proper science soon.