interview

The evolution of biomaterials

How did you become interested in
working with biomedical materials?
In 1974, I had just begun a postdoctoral
position with Judah Folkman at Childrens
Hospital and Harvard Medical School,
and I needed to solve a problem: to isolate
what would be the first angiogenesis
[growth of blood vessels] inhibitor. To do
this, I wanted to develop a corneal assay
for stopping blood vessel growth in a
rabbit; part of this involved the creation of
a polymer system that could be embedded
in the cornea to continuously release
macromolecules that were angiogenesis
inhibitors for many months. In 1976, we
published this research in Science1 and since
then the area of angiogenesis inhibitors has
become an enormous field. Over 1 million
people use such inhibitors every year to treat
cancer or macular degeneration, a leading
cause of blindness.
What are your principal research
interests in the biomaterials area at
the moment?
We continue to work in drug delivery
and controlled release. Some of the newer
things we are doing in drug delivery
include creating nanoparticles that are
targeted to specific cells in the body, and
the delivery of new molecules, such as
siRNA [small interfering RNA], that can
be used to turn genes off. We are also
creating specifically designed nanoparticles
containing DNA to allow gene therapy on
many different cell types. Finally, we are
carrying out work on tissue engineering
combining materials and cells to create new
tissues and organs in the body. This work
is leading to the creation of new skin and
other tissues.
What work are you most proud of from
your time working on biomaterials?
There are many areas Im proud of. One of
these is our early discovery in 1976 of how
polymers could be used to continuously
release macromolecules2. Another area
is the synthesis of new materials that have
led to new treatments for brain cancer
and other diseases. A third one is tissue
engineering. In 1983, Jay Vacanti and I
had an idea that if we designed polymer
444

StU ROSNER PhOtOgRaPhy

Robert Langer has spent more than 30 years working with biomaterials and has seen their development
from simple implants to complex multifunctional interfaces with the body. He shares his vision of the
fields origins and what the future holds with Nature Materials.

fibres in the right way, cells might be

able to organize themselves on the fibres
to create organs and tissues and that
turned out to be true. Were proud of
this work because these studies showed
that you could make three-dimensional
polymer scaffolds and use them in such a
way to help organize cells to make tissues.
This approach has been widely used in
academia and industry as a cornerstone of
regenerative medicine. I believe our 1993
Science paper on this topic has been cited
over 2,000 times3.
Some tissues, clinically based on this
concept, are already available such as
skin but there are still many others that
would be good to make, for example spinal
cords, livers, pancreases and hearts. So we
continue to work on all of the aspects that
are required: cell biology, immunology and
materials. The more complex organs
heart, liver, and kidney are a bigger
challenge. Increased complexity often
means more cell types, which increases the
difficulty of making the tissues or organs.
How do you approach the challenge of
achieving this complexity?
Materials are just one part of it. One might
want to have a vascular supply, so one could
use microfabrication as a manufacturing
technique to build in microvessels. You may
want to synthesize highly elastic, strong
biomaterials because some tissues, such
as the heart, require elasticity. Recently,

Lisa Freed, I and our colleagues showed

that this approach could be useful in tissue
engineering 4 by making an accordion like
polymer structure seeded with heart cells
that could create new heart tissue (Fig. 1).
What has been the most impressive
development in tissue engineering in the
past five years?
The whole area of stem-cell biology is one
of the most exciting developments: trying
to understand how to control stem-cell
behaviour, and how you can convert regular
cells into stem cells such as the IPS
[induced pluripotent stem] cells. These
kinds of areas are very important. Though
researchers have achieved a lot, the way
they have achieved this is generally by using
viral vectors [to deliver genetic material into
cells]. I hope the work that we and others
are doing will enable a way to do these steps
with non-viral vectors.
We have been collaborating with
Rudy Jaenisch at the Massachusetts Institute
of Technology, and he is a pioneer with
IPS cells, although he started with viral
vectors the same as everyone else. We have
created materials that are very potent at
gene therapy and so we hope we will be
able to use these materials to replace viral
vectors and this, of course, would be safer. In
particular, Dan Anderson and others in our
lab are synthesizing new polymers that can
deliver genes very effectively and yet are still
quite safe.
What important factors do you keep in
mind when designing biomaterials?
There are several factors. The materials
themselves can be an inspiration you
might get an idea from what the tissue
is like; what the strength and elasticity
should be; what the degradation should
be; whether you want a more complex
microstructure because you might be
using multiple cell types. One example that
requires a more complex microstructure
is the liver, which has five cell types plus
a complex network of blood vessels. To
work on this, we have been collaborating
with Jeff Borenstein at Draper Labs using
microfabrication technologies to create a
microvasculature structure.

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2009 Macmillan Publishers Limited. All rights reserved

interview
a

Figure 1 | accordion-like honeycomb scaffolds yield anisotropic mechanical properties similar to native myocardium. a, Schematic diagram of the honeycomb
design. Scale bar 1 mm. b, Realization of the structuring in polymeric scaffold. Scale bar 200 m. c, Preferentially aligned heart cells grown on the scaffold in vitro.

What do you think have been the pivotal

moments and products that have shaped
the biomedical industry?
The artificial kidney was important as an
early biomaterial-based implant. Heart valves
have also been very important. But there are
a lot of areas; biomaterials have a central role
in almost any aspect of any implant. They
have had a key role in medical devices, drug
delivery systems and many other implants.
Moving towards degradable implants
has been an attractive research direction
because many of the problems that might
evolve with non-degradable materials
would go away. In tissue engineering, we
use a temporary biodegradable scaffold and
ultimately you generate natural tissue and no
synthetic polymer.
Have there been any major set-backs in
the industry?
The biggest set-backs have been legal ones.
I dont think they were justified, and they
were not decided on by people who really
understand the field. Certainly, Dow Corning
going bankrupt in the nineties because of
lawsuits against breast implants had a bad
effect. And Dupont had to give over millions
of dollars in legal expenses because they
supplied the materials for another company
that was making an artificial jaw; that
company went out of business, and lawsuits
were made against Dupont even though they
did nothing wrong.
Issues like these have stopped companies
from becoming involved with biomaterials
because of liability. This happens particularly
in the US, probably more than other countries.
For example, the National Research Council
publication Rising above the gathering
storm states that more money is spent on tort
litigation in the US than on all research and
development. I doubt that could be said for
any other country in the world.

Which therapeutic areas have been

helped most?
Heart valves and artificial dialysis are
certainly among them. Biomaterials are
everywhere. They help in controlled release
systems in the pharmaceutical area, an
enormously broad field that has a huge
influence. Biomaterials affect hundreds
of millions of people who use devices,
diagnostics and drug-delivery systems.
Examples are stents and pacemakers in terms
of devices, blood tests for diagnostics, and
injectable microcapsules and transdermal
systems for drug delivery. Biomaterials are a
central component of all of these systems.
What are the short-term goals of the
biomaterials industry?
I dont think there is a single goal: there are
a variety of goals. Creating materials that
can solve different problems it could be
a better bioprosthesis, it could be stronger
materials there are all kinds of challenges,
and each area has its own.
For instance, in the treatment of cancer
and heart disease, one of the challenges is
coming up with a way to do targeted drug
delivery, to target drugs right to the cells of
interest. In many areas youre also looking for
materials that are highly biocompatible and
non-inflammatory. Finding a material that is
extremely biocompatible is a real challenge.
Moving into the longer term, I think by
2020 we will see new drug delivery systems
with nanoparticles that can be targeted to
specific cells or tissues.
some biomaterials are now beginning
to come through clinical trials, appear on
the market and even be used in therapies.
Which products are you most excited to
see being used?
There are a few. One set of products is
degradable stents these are tubular

nature materials | VOL 8 | JUNE 2009 | www.nature.com/naturematerials

2009 Macmillan Publishers Limited. All rights reserved

constructs inserted in veins and arteries

to provide support and keep them
open composed of lactic/glycolic acid
copolymers, certain polycarbonates or other
materials. A second one is nanoparticles
for targeted drug delivery, composed of
block copolymers, cyclodextrins or other
materials. And even though a little further
off I would expect clinical trials to start in
a year or two there are implantable silicon
microchips with arrays of glucose sensors to
enable long-term glucose measurement. All
of these systems could initiate fundamental
changes in medical therapies.
Based on what were seeing today, what
biomaterial products do you think we can
expect to see coming to the market and
being used in the next two to three years?
I think we could see degradable stents used
in human therapies in this time frame.
Targeted nanoparticles will also be used, but
may be a little further off. We could also see
lipid-based systems for siRNA delivery.
How do you feel rewarded by working in
this field?
Its very rewarding to see that the research
we are doing is helping peoples lives. As I
work at a hospital as well, I am sometimes
able to see those effects first-hand. I feel
biomaterials is a very important area that
has helped and can help an enormous
number of people.
References
1. Langer, R., Brem, H., Falterman, K., Klein, M. & Folkman, J.
Science 193, 7072 (1976).
2. Langer, R. & Folkman, J. Nature 263, 797800 (1976).
3. Langer, R. & Vacanti, J. P. Science 260, 920926 (1993).
4. Engelmayr, G. et al. Nature Mater. 7, 10031010 (2008).

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