TR: What are the major technical trends in biomaterials for drug delivery?
LANGER: One area my lab is working in is designing polymer nanoparticles to deliver DNA efficiently in gene therapy. This is basically a tiny polymer sphere with DNA inside that you want to get into a cell. It’s very challenging, but the plus is that you may get some significant safety advantages over the gene-delivery systems that are now in clinical trials, which make use of viruses.
Further out, we’re thinking about things like “smart” systems that can deliver drugs in response to specific body signals. You could have an implantable biosensor that can detect glucose levels and tells a drug-delivery implant to release insulin when it is needed.
TR: What about permanent implants?
LANGER: A lot of people think the ultimate solution will be smart systems that behave a lot like the part of the body you are trying to replace. With artificial blood vessels, we are thinking now about approaches where you could attach molecules that might be desirable, say, something to attract endothelial cells [the cells that line normal blood vessels] and help create a natural lining. In a sense, I think what you want to do is get rid of materials-you want them to do their job and then disappear, or become invisible.
TR: You’re talking about combining synthetic materials with proteins or cells?
LANGER: Right. The merger of engineering and biology is very important today. There is a real revolution going on in the biological sciences, and the associated engineering opportunities are enormous. In a field like tissue engineering, it’s the integration of knowledge from cell biology, materials science and process science that you need to create a new tissue.
TR: You mentioned tissue engineering. Can you explain what this field is about?
LANGER: The approaches that we use start from the observation that if you take cells and inject them into the body at random, nothing happens. But if you take those same cells and line them up close enough together, they can form tissue structures. If you take mammary epithelial cells and line them up, they will organize and make milk.
The first engineered tissue was skin, which you can grow on a two-dimensional surface. But in 1986, along with Jay Vacanti [a pediatric surgeon at Massachusetts General Hospital], I decided that if you really wanted to make tissues-bone, cartilage, liver, you name it-you could use synthetic polymers and put them into three-dimensional structures. That provides a template for the cells to grow and allows them to reform structures.
TR: What kinds of tissues are you making in your lab?
LANGER: We are trying to make cartilage by growing cartilage cells on degradable polymer foams. We can design the foam in the shape of a human nose, for example, then place cells throughout the foam and grow it in a bioreactor. Over time, the cells produce extracellular matrix which provides strength, and the polymer dissolves. The result is pure cartilage in the shape of a human nose.
TR: Has this kind of work progressed outside of the lab?
LANGER: This field is growing pretty fast. Several tissue-engineered skins are approved by the FDA [for treating burns or wounds]. Cartilage is in clinical trials, and liver is in clinical trials [a device for liver-failure patients in which blood is passed outside the body through a cartridge filled with liver cells]. So there are a number of things that have moved out of the laboratory. And before that, in animals, there are probably about 20 tissues being worked on, including heart valves, blood vessels and intestine. All of these are grown on polymer scaffolds.
TR: Will we be able to regrow very complex organs, like hearts?
LANGER: I am sure with enough time, perhaps decades, all these things will be figured out. But right now, it’s very difficult. It really depends on the complexity of the tissue, and our understanding of the biology and engineering challenges, and also how perfect you need the system to be. Though the FDA has approved tissue-engineered skins, those are not absolutely perfect skins-they’re just better than anything else you can do. And there are cell types, like nerves, that have proven to be really complicated. We are just starting to learn things from biology that are enabling us to do a little bit better in this area.
TR: More than 50 companies have licensed your inventions in polymer chemistry. How does it feel to help create new industries?
LANGER: It feels good. My goal has always been not just to write the scientific paper or file a patent, but to really push some of these ideas to the point where they will affect people’s lives in a positive way. And it takes a long, long time for the most part. When you start doing these things, no one believes in them, nobody wants to fund them, and companies don’t want to do them. And you get criticized a lot.
The important thing to remember is it’s not going to be by the efforts of one person or one lab that these problems get solved. What makes these approaches work is ultimately having hundreds or thousands of people working on them. And that is what has happened in drug delivery, and that is what is starting to happen in tissue engineering and bioengineering in general.
TR: What does the future hold for you?
LANGER: The big thing for me is to keep coming up with these early-stage ideas, which people may call crazy as they called some of the other ideas crazy 10 or 15 years ago. For instance, we’re working on implantable microchips that can release specific drugs or vaccines into the body on demand by telemetry. One of my graduate students, John Santini, is building a drug-delivery chip with 1,400 reservoirs, in which you could put 1,400 different substances, or many doses of one drug. You’d probably put a little microprocessor on it and signal it from the outside. I want to move this far enough along so that, again, we’ll end up seeing a lot of people working on it. For me, ideas are like children growing up. I want to nurture them so they are stable and so they will happen.