Robert Langer on tissue engineering

Jennifer Leonard: You are one of the most prolific inventors in medicine today. Tell me about some of the patents you hold.
Robert Langer: We have quite a few patents in different areas. Some of them, for example, relate to polymer systems that continuously release molecules of a certain size. Another is on brand new kinds of plastics. Another is on the local delivery of drugs, for cancer or other diseases. Another is on plastics that can change their shape. Another relates to tissue engineering. Some new ones are in gene therapy delivery.

JL: What are some of the applications of your research into the delivery of drugs at steady, controlled rates?
RL: There are quite a few, and, of course, the field goes far beyond what we do ourselves in the lab. But some drug delivery systems you might see are transdermal patches – patches that could deliver nitroglycerine or nicotine, to prevent people from smoking cigarettes. Drug delivery also involves drug-eluting stents, where a polymer is placed on the outside of the stent; these are like Chinese finger puzzles, and they’re put in a patient to keep the blood vessels open. We’ve been involved in implants, or injectable microspheres, that could release human growth hormone, or hormones that might be able to aid in treating prostate cancer.

JL: When you first presented your ideas to the medical community about polymer systems that release molecules into the body, how were they received?
RL: A lot of people felt that substances of only a certain size could move through plastic. And I needed to figure out a way to get substances of a much bigger size through the plastic. I finally figured out a way to do that, and people just didn’t think it was possible. Conventional wisdom told them that trying to move through plastic was like, say, you or I trying to pass through a brick wall. See, the thing is, you could have a brick wall, or you could have something like Swiss cheese. Nothing could get through the brick wall, of course. Things will get through the Swiss cheese, certainly, but too quickly. What we were able to do was make something that had open pathways, but with tortuous routes that were narrow and incredibly winding, so it took a very long time to get through them.

JL: How did you come to develop the chemistry microchip?
RL: I got this idea about ten years ago from watching a television show on how computer microchips were made. I thought, rather than have an electrical microchip for the computer industry or your television, maybe we could make a chemistry microchip. I thought we could build into a little chip thousands of little wells that could have, literally, thousands of different drugs if you needed them, or thousands of different doses – like a pharmacy on a chip – that could one day give the patient whatever he or she needed at the appropriate time.

JL: How is the drug released from the microchip?
RL: If you make what we call an "active chip," you can control it by telemetry, the same way you open up a garage door, by radio frequency. You have a little device in your car, in the case of the garage door; you could have the same kind of device in a wristwatch or something you can hold in your pocket, which could open up the specific well in the chip containing the specific drug or the specific dose of drug that you’d want.

JL: What thought processes do you go through when it comes to designing biomaterials?
RL: I try to ask the question, "What do you really want in a biomaterial, from an engineering standpoint, from a chemistry standpoint, from a biology standpoint?" And then I ask, "Could you design it from scratch, from first principles?" That’s what we’ve done. We’ve asked different chemistry questions to see if we can actually make these kind of things.

JL: How does it feel to know that your polymer wafers are going into people’s brains?
RL: What’s great is that I’ve met patients who have been treated with this innovation and it’s a great feeling for everybody that has participated in the project – in the lab, and myself – to see that these wafers have provided a way to relieve suffering and prolong life.

JL: How does the wafer work?
RL: We designed a special polymer from scratch, which dissolves the way a bar of soap does. The chemistry that we’ve made is such that we can make it last anywhere from a day to over six years, or any time in between. In particular, what we’ve done is make it last for about a month. The neurosurgeon who treats the patient (we’ve done this a lot with neurosurgeon Henry Brem, at Johns Hopkins) operates on the brain, removes as much tumor as possible, and then inserts these little wafers, the size of small coins. These wafers slowly dissolve right at the site of whatever remaining tumor exists, and they locally deliver the chemotherapy. In contrast to conventional chemotherapy, which goes all over your body, causing a lot of toxicity to different organs, this is local delivery, right to the site of need.

JL: Go back to the days when you and Dr. Jay Vacanti first tossed around the idea of actually growing new organs from scratch.
RL: Jay has been a good friend of mine for a long time. About twenty years ago, when he directed the Liver Transplant Program at Boston Children’s Hospital, he came to see me because he wanted to solve the problem of too many people dying while awaiting new livers. We started talking about how we could come up with a way to overcome the problem of donor shortage. We wondered if we could design an artificial liver, then came up with the idea of using a combination of polymers and cells in certain configurations. This line of thinking ultimately led to the design of new tissues.

JL: How is tissue engineering different from other fields of cell culture?
RL: Doing cell culture alone, you can study things and learn things about cells and culture, but you wouldn’t make a new tissue. Tissue engineering, if successful, ultimately enables you to make a new tissue, like new skin that you could actually put on a patient or, someday, new bone or cartilage or blood vessels or heart muscle. These are often three-dimensional structures that are vascularized. They sometimes have multiple cell types, so they are more complex structures to engineer.

JL: How does a biodegradable polymer scaffold function?
RL: Say you’d like to make a particular structure, like an ear or skin. You first take the polymer and form it into the desired shape, then you take the cells from the patient, or stem cells, and place them on the polymer fibers. These cells grow and ultimately form the structure that you want them to form. Finally, these new tissues are put into the body and the plastic scaffold degrades away.

JL: Where can some of this work lead?
RL: We hope that one day we might be able to take a patient with a damaged spinal cord and make him or her well again, or at least improved by these technologies. We’ve worked out ways to use polymer scaffolds where you could actually help patients; in this case the patients are rats, but basically we’re able to take rats that couldn’t walk and then a hundred days later find them actually walking.

JL: In the next ten years, what do you have to look forward to in both drug delivery and tissue engineering?
RL: In drug delivery there are already a lot of products helping patients, and I think we have the opportunity to see many, many more of these. You’ll see more patches and new aerosols, which will take the place of insulin shots – or at least lessen the need for them. You’ll see all kinds of new advances in drug delivery. With tissue engineering, we’re just now at the point where new skin can be made for patients, and I think before long we’ll see new cartilage for patients too, maybe even new bone and organs.

Robert Langer is a biochemical engineer at the Massachusetts Institute for Technology in Cambridge, Massachusetts.