Materials in the New Millennium: Responding to Society's Needs (2001)

The second topical session examined the role of materials in health and biotechnology. The overview talk in this session was presented by Robert Z.Gussin of Johnson & Johnson, where Dr. Gussin is the corporate vice president of science and technology. In that position, he serves as the company’s chief scientific officer. He also holds adjunct professorships in pharmacology at Michigan State University and the University of Utah.

Galen D.Stucky of the University of California, Santa Barbara, provided a technical perspective. Dr. Stucky is a professor in the Department of Chemistry, the Materials Department, and the Biochemistry and Molecular Biology Program of the University. The focus of his recent research has been on understanding how nature assembles organic and inorganic biomaterials and the molecular design and assembly of hierarchically structured three-dimensional devices.

Robert Langer of the Massachusetts Institute of Technology provided a second technical perspective. Dr. Langer is the Kenneth J.Germeshausen Professor of Chemical and Biomedical Engineering at MIT. His research interests include polymers for controlled release of proteins and macromolecules and the development of new biomaterials. He is a member of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.

John T.Watson of the National Institutes of Health (NIH) described a government view. Dr. Watson is the head of the Bio engineering Research Group and acting deputy director of the Division of Heart and Vascular Diseases of the National Heart, Lung, and Blood Institute of NIH. His education includes graduate degrees in both mechanical engineering and physiology. His research interests include medical implant design and science, biomaterials, imaging, and heart failure. He is a member of the National Academy of Engineering.

The session ended with a panel discussion. The following are summaries prepared by the editors who adapted them from the remarks made by the individual presenters.

Biomaterials incorporated into medical devices have had at least as great an impact on health care in the twentieth century as have pharmaceuticals. Virtually all types of material systems have been used in health care applications, including metals and alloys, ceramics, polymers, composites,

and biologically derived biomaterials. Both bulk and surface properties must be carefully selected and designed for suitability of service and compatibility with biological systems.

Among metals and alloys, there are four common systems: stainless steels, cobalt-chromium alloys, titanium and its alloys, and more recently some aluminum-zinc systems. In hard tissue, metals and alloys are used for fixation and joint replacement. In the vascular system, they are employed in stents and heart valves. Stents are also used in the bile duct and urinary tract. Dental applications may involve some of these same alloy systems as well as gold, amalgams, and tantalum. Platinum and platinum-iridium alloys are used frequently in implantable conductors, such as pacemaker leads.

The most common biomedical ceramics are alumina, zirconia, silicon nitride, and carbon. These materials may be completely bioinert, surface-active, or fully resorbable. Bioinert materials are often used in orthopedics. Surface-active materials, such as bioglas and ceravital, dense nonporous glasses, and hydroxyapatite, are used in coatings, in dental applications, on bone plates and screws, and sometimes for bone filling. Resorbable ceramic materials, including phosphates, oxides, and corals, are used to repair bone damage, for bone filling, and even for drug delivery.

A wide range of polymers are used in medical devices, both implantable and extracorporeal, with applications from kidney dialysis to heart valves. They can be inert, surface-modified, degradable, erodable, absorbable, or resorbable. Degradable and erodable materials are distinguished from absorbable and resorbable materials in that the latter leave no residue after their chemical breakdown. As a result there is no long-term foreign-body reaction and no nidus for microbial colonization. Historically, suture materials have been the most successful application of resorbable polymers. Future applications will include scaffold materials for tissue engineering, as well as vehicles for implantable drug delivery.

Composite materials are used most frequently in hard-tissue applications, including ceramic composites for dental applications and fiber-based composites for orthopedics.

Biological materials fall into several categories: hard-tissue, soft-tissue, blood-derived, plant-derived, and other naturally derived chemicals. The most common examples are collagen-derived materials used for hemostasis, tissue filling and enhancement, drug delivery, and other applications.

Recent research trends that will challenge materials designers include the development of implantable biosensors, artificial muscles, drug delivery hydrogels, wound dressings, sealants and adhesives, tissue augmentation and regeneration, immunoisolation devices, and specific surface chemistry modifications. Many of these trends will be pursued through the broad field of tissue engineering. Skin, bone, and cartilage applications have been most successful to date, but the focus of research is shifting toward tissue-engineered organ replacements. In general, the objective of tissue engineering is to reinstate tissue function, facilitate tissue transplant, provide localized drug delivery, facilitate organ reconstruction, and implement cell and gene therapy.

In summary, advances in biomaterials design have great potential for contributing to advances in health care.

The biological world has much to teach us about the synthesis of materials, not just materials for medical applications, but also so-called biomimetics or bio-inspired materials.

A living cell can be considered a tiny materials factory, a single system capable of synthesizing and processing materials with a three-dimensional hierarchical structure. Synthesis takes place on the nanoscale and can assemble composites with an asymmetric distribution of reinforcing materials in an organic matrix. Interconnects can be managed at a molecular level. The “factory” is self-repairing and self-correcting and performs much of its synthesis in a parallel-processing mode.

One such biological factory is the diatom, which can both produce silica and extrude polysaccharide. In fact, diatoms extrude polysaccharide through submicron pores, an enviable example of nano-processing. Aida, in Japan, has demonstrated a similar catalyzed microextrusion polymerization process of polyethylene resulting in improved structural properties.

This biological example should inspire and encourage us to pursue nanoscale chemistry and processing. Specifically, we should be encouraged about the prospects for molecular design and processing of three-dimensional silicate surfaces and the prospects of doing such processing in biologically compatible conditions rather than at elevated temperatures. One biologically inspired system is an organic matrix block copolymer nanocomposite with potential applications in optical limiter coatings, wave guides for microlaser arrays, sol-gel encapsulation of enzymes, and bio-sensors.

Other biological inspirations include species with so called “electrocyte” cell arrays capable of delivering electrical power in excess of a kilowatt for substantial periods, such as 80 seconds. The three-dimensional hierarchical structure of so many biologically produced materials has already inspired some novel polymeric MEMS applications using two-photon optical curing with resolutions of 0.2 microns laterally and 0.28 microns in depth.

To date the overwhelming majority of materials used in health care applications, including alloys as well as polymers, were derived originally for nonmedical purposes. For example, the diaphragm material used in the first implantable artificial heart was a polyurethane of the same type used in women’s undergarments. Now more than ever, we need a process of rational design for materials for in vivo use.

Certain examples of this new paradigm for materials selection and design already exist. In drug delivery, polyanhydride materials were designed to be

surface rather than bulk eroders. Therapeutic chemicals trapped in a polyanhydride matrix can thereby be released at a controllable rate. Depending on the polymer design, complete dissolution can be programmed to take from two weeks to four years. This technology has already been applied for brain cancer therapy, with early results showing as much as a fivefold improvement in the survival of tumor victims. The technology has been approved by the Food and Drug Administration.

Another example of materials designed for in vivo application is the so-called chemical microchip. This device permits externally controlled administration of microdoses of pharmaceuticals at the specific implant site.

A third example is in the growing field of tissue engineering. For many tissue-engineered products, cells are grown on a scaffold of polymer materials, such as polylactic-glycolic acid (PLGA). With intentional design of new scaffold materials, one can envision changing the rate of degradability, improving biocompatibility, designing suitable physical properties for the substrates, and even being able to attach specific ligands selectively. Our research team’s inventory already includes at least 24 different tissues.

As Dr. Langer noted, current synthetic materials for in-vivo applications were not initially designed for such purposes and are therefore imperfect in their biomedical application. Another concern is that biomaterials research has relatively low visibility. When developing new materials systems, the research and development community should start with patient needs rather than looking for solutions off the shelf. Patient needs that will motivate new material designs include quality of life, performance, safety, failure risk, lifetime, and need for replacement. Recent work on a synthetic ion channel has raised hopes for new materials that will emerge from the marriage of nanotechnology and biology.

Since 1997, the National Institutes of Health has become increasingly active in support of biomaterials research. The Bioengineering Consortium initiated in 1997 is intended to support bioengineering partnerships performing design-directed research. The NIH-sponsored Biomaterials and Medical Implant Science Coordinating Committee met in early 2000 to discuss ways to improve implant performance. It recommended a national educational program and an implant-retrieval information system.

Question: The so-called “valley of death” between research and commercialization seems especially troublesome in the biomedical field. Can you comment on steps to overcome the difficulty of going from research to practice?

Langer: Biomedical engineering departments in academia are trying to focus more on applications and are beginning to have some success. Small biotechnology start-up companies are also becoming increasingly effective in pulling technology from the universities.

Watson: It would be helpful if engineers in all disciplines had some background in biology.

Gussin: I, too, would recommend some background in biology for engineers. Johnson & Johnson is deliberate about assembling teams that include both engineers and clinicians.

Q: What about the difficulties associated with FDA approval? How limiting are these?

Langer: The FDA approved polyanhydride with a total development cost of something under $10 million. The FDA can put good ideas on a fast track.

Comment: It is important to note that the FDA approves devices, not materials.

Q: The university engineering curriculum is already quite full. To make room for biology in the curriculum, what would you take out?

Watson: Take out chemistry.

Langer: Biology is already part of the curriculum at MIT for all engineers.

Q: But making room for biology in the MIT engineering curriculum meant eliminating electives unless freshmen arrive with advanced placement credits in chemistry.

Q: What about the financial risk to corporations (such as Dow Corning) that could supply or develop new implant materials?

Watson: Dow Corning changed its design from a proper one to a poorer one and began to experience design failures. I do believe that certain disorders suffered by women with failed implants are related to the silicone materials.

Gussin: Because of the threat of litigation and the fact that for large materials producers the biomaterials market is small, businesses are reluctant to look at new materials except perhaps those that could have an impact on life-threatening conditions.

Comment: Many large companies have pulled out of their activities in biomedical research, development, and production. We should be concerned that some of these, the very best in our nation, are not participating in this important field.

Q: Is the NIH interested in supporting nonmedical research built on a biomaterials foundation—sensors based on antigen-antibody interactions, for example?

Watson: Probably not, unless the applications occur as a direct spinoff from a biological or biomedical research effort.

Q: How do we work the problem the other way?

Stucky: Develop and offer interdisciplinary courses at the university level. Make sure future workers understand two languages, engineering and biology. Look for and accommodate spinoffs in both directions, biomedical and nonbiomedical.