CHAPTER SEVEN
Bioinspired and Bioderived Materials

CHAPTER SUMMARY

The Panel on Bioinspired and Bioderived Materials focused on how the integration of biology and the physical sciences could result in greatly improved, lightweight, multifunctional materials for DoD. Materials derived from biology, for example, biological molecules as the active element in sensors, and materials inspired by biology—for example, layered, hierarchical, abalone shell-like composites as lightweight, tough armor—were considered. The potential impact of applying biological paradigms to the development of materials to meet DoD requirements was reviewed in depth.

Biological systems have clearly shown that large numbers of molecules, structures, and systems in living organisms possess attractive materials properties that are beyond the reach of current nonbiological synthetic approaches. Many of these molecules, structures, systems, and natural fabrication processes could serve as the basis for synthetic materials with enhanced properties. The challenge of using living organisms as a model for materials for future defense needs lies in identifying defense applications and then understanding and manipulating the biological systems to solve them. However, the integration of biology and materials science is hampered by discipline-driven education and the historical separation of biology and materials science in academic, industrial, and military laboratories.

This chapter details specific DoD opportunities in the areas of structural materials, functional materials, materials for chemical and biological warfare, wound healing, and human perfor-



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CHAPTER SEVEN Bioinspired and Bioderived Materials CHAPTER SUMMARY The Panel on Bioinspired and Bioderived Materials focused on how the integration of biology and the physical sciences could result in greatly improved, lightweight, multifunctional materials for DoD. Materials derived from biology, for example, biological molecules as the active element in sensors, and materials inspired by biology—for example, layered, hierarchical, abalone shell-like composites as lightweight, tough armor—were considered. The potential impact of applying biological paradigms to the development of materials to meet DoD requirements was reviewed in depth. Biological systems have clearly shown that large numbers of molecules, structures, and systems in living organisms possess attractive materials properties that are beyond the reach of current nonbiological synthetic approaches. Many of these molecules, structures, systems, and natural fabrication processes could serve as the basis for synthetic materials with enhanced properties. The challenge of using living organisms as a model for materials for future defense needs lies in identifying defense applications and then understanding and manipulating the biological systems to solve them. However, the integration of biology and materials science is hampered by discipline-driven education and the historical separation of biology and materials science in academic, industrial, and military laboratories. This chapter details specific DoD opportunities in the areas of structural materials, functional materials, materials for chemical and biological warfare, wound healing, and human perfor-

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mance enhancement. Each section contains a discussion of how an identified materials challenge might be met. The panel concluded that Biological toughening mechanisms offer a route to the next generation of lightweight, tough materials. Preservation of the biological function of biological molecules is a key driver for the next generation of biologically enabled devices. In vivo detection strategies to identify toxins and pathogens, including masked agents, may make it possible to detect a single agent molecule. The panel identified the following priorities for DoD R&D investments: Improve fundamental understanding of the relationships between biological structure, properties, and evolution and materials design and synthesis. Increase communication of DoD material needs to biological and physical scientists. Pursue basic research into biological molecules, structures, systems, and processes to lay the groundwork for their use, or their use as models, in meeting DoD materials needs. Identify and produce biocompatible materials to enable in vivo implantable devices. Develop packaging technologies to preserve the biological function of biologically enabled devices. In conclusion, biology can suggest directions for addressing many DoD needs in the next several decades. In some areas (e.g., improved battlefield medicine and identification or interdiction of biological warfare agents), solutions may be found in specific biological molecules, cells, or systems; in other cases (e.g., smart materials or lightweight structural materials), biology may point the way to improved strategies for material design and synthesis. Where biological molecules or cells are the active component of a device, the challenge to the materials community is not only incorporation of the sensing entity but, also, and perhaps more important, the preservation of biological function in a nonbiological environment. The common theme for all these technologies, research areas, and applications is to use biological paradigms for the solution of problems of materials design, materials synthesis, and systems assembly.

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INTRODUCTION Biological systems represent a successful strategy for the design of materials, the fabrication of parts and components, and the integration of parts into systems that meet complex performance criteria in a variety of environments. These evolutionarily engineered realities have emerged slowly. The possibility of incorporating the principles of evolutionary “strategy” into modern engineering and scientific practice is emerging in materials science and engineering. This chapter is concerned with Identification of biologically derived materials for improved warfighting effectiveness, How applying biological paradigms will affect the development of materials meeting DoD needs, and Identification of biologically inspired materials for improved warfighting. The current materials science paradigm is that a material’s performance is uniquely related to its structure, and the structure of a material reflects the totality of its processing history. This insight allows processes and products to be developed based on scientific principle rather than purely empirical methodologies. Once the process-structure-property-performance database is established, a single material may be processed to satisfy a variety of applications. An example of this is the production of molecularly identical, morphologically distinct poly (ethylene terephthalate) fibers for applications as diverse as pliant textile yarns and stiff reinforcing cords for tires. Materials application in medicine has historically been highly empirical; seldom are materials primarily designed for biological or in vivo applications. The application of the methods of materials science to the understanding of biological materials should prove productive in finding new materials for DoD. An overview of the subject matter and disciplines treated in this chapter is shown in Figure 7-1. The integration of biology and materials science is hampered by the fact that education is discipline-driven and by the historical separation of biology and material science in academic, industrial, and even military laboratories. This has created problems, among them incompatible usage of terminology, incompatible approaches to problem solving, and divergent cultural viewpoints, that can render interaction difficult.

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FIGURE 7-1 Schematic overview of subject matter and disciplines covered in this chapter. The value of successfully integrating materials science and engineering with biology is difficult to estimate accurately but it represents at the least an opportunity to cross-fertilize and broaden each community’s paradigms. Many of the examples cited below represent either the reality or the promise of this integration. DOD NEEDS FOR BIOINSPIRED AND BIODERIVED MATERIALS Mankind has been using biological materials for defense purposes for millennia: wooden staffs for spears or ax handles, vines for ropes, snake venom or plant extracts for biological weapons, shaped bone for tools and weapons. More applications are sure to come. As discussed below,

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multilayered abalone shell could point the way toward a new tough, lightweight vehicle armor, and spider silk fibers could become the basis for enhanced protection of personnel. Organic and biological electronics could lead to extremely light laptop computers and other devices. Insects may be seen as analogs of autonomous vehicles, equipped with composite smart armor featuring a variety of sensors and receptors. Conversely, a variety of biocompatible materials could be implanted (e.g., as hearing aids, lenses, artificial blood) to enhance soldier performance. Billions of years of evolution have given mankind a wide variety of biological solutions to materials problems. The challenge lies in identifying relevant defense applications and understanding and manipulating the biological systems to solve them. It must be borne in mind, however, that the actual use of biological materials or materials that mimic biological systems lags far behind our enthusiasm for them. With a few notable exceptions, these biomolecular materials remain the materials of the future: despite an extraordinary rate of progress in the field, they are likely to be materials of the future for a number of years. This does not mean that the field should be ignored by those focused on defense applications, awaiting a future when opportunities for applications might appear. Recent research has vastly increased our knowledge and understanding of biological materials and how their unique properties arise from their structure. New tools allow us to modify biological materials for our needs or to synthesize, de novo, materials that are based on biological principles. Nevertheless, there is a need for basic research to improve this understanding. More important, applications arise not from a linear progression of basic to applied research but from the vigilant and creative observation of basic research with an eye toward the unexpected, the unplanned, serendipitous breakthrough. Thus it is fair to say that basic research in all areas of biology must be pursued because there is no way to predict which discoveries in which fields will have important impact. The greatest problem lies in linking those who discover intellectually interesting things to those who know of and are charged with meeting specific needs. It is not easy to find people who are both aware of current science and know the needs of the military. There is no doubt that there is much already in the basic science literature that could have defense applications but that has not yet been “discovered” by potential users. This will continue to be true as the pace of scientific discovery accelerates. To bridge this gap, basic researchers must be made aware of defense needs, so that they will notice potential applications when the underlying discovery

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is made; chance favors the prepared mind. At the same time, defense materials researchers must be closely linked to the basic research establishment so that they can extract potential applications from the flow of apparently nonuseful fundamental discoveries. But the future lies in the biology. This chapter describes a wide variety of molecules, structures, processes, and concepts in biology that can reasonably be thought to have, at some point, a defense application. In some cases, research toward applications has made good progress. In many other cases, however, at this time we cannot even begin to develop those materials. In fact, in many cases we can list more barriers than routes to materials development. However, the great discoveries are those that even the most visionary cannot envision. Any concept that does not violate a law of thermodynamics should be regarded as possible. The shelves of military warehouses and consumer stores are stocked with valuable useful products whose function was regarded as impossible not many years ago. “Computers in the future may weigh no more than 1.5 tons.” —Popular Mechanics, 1949 What, then, do living organisms do that might be exploited for defense applications? What do we know now about these molecules or processes and what do we need to understand to bridge the gap to application? First and foremost, there is a clear need for better understanding of structure-property-function relationships in these materials. Second, it must be kept in mind that biological activities occur on the molecular level. Even the most complex of behaviors can (or will, once we understand them) be explained in terms of the presence or absence of specific molecules and the interactions among them. Further, it must be kept in mind that nature does not optimize biological materials and processes. Nature makes them just good enough—first, because perfection is not necessary for survival; second, because optimization of one process or structure might be detrimental to another; and third, because biological systems have evolved in the presence of a limited number of the 92 naturally occurring elements, within a narrow range of pH, temperatures, and pressures, and with the requirement that neither the product nor the intermediate molecules along the “production” path be toxic. Thus it is reasonable to argue that if we were to loosen the constraints, as we can when operating outside the organism, we might do better.

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The greatest limitation to the mimicking of biological systems in materials and processes for defense applications lies in our insufficient understanding of these systems. One can argue that a more complete understanding should lead to many useful applications. On the other hand, it is equally clear that there are severe limitations on the use of biological molecules, structures, and processes. Biology does not in general thrive under extreme conditions. Biology limits itself by not making use of the vast majority of naturally occurring elements. Biological structures and systems are extremely complex, far more so than their synthetic analogues, and are therefore extremely difficult to manipulate—consider bone compared to titanium or even sophisticated alloys. These barriers could yield to our increased understanding but might also be avoided if the systems to be used were simplified, for example, in synthetic “cells” with artificial membranes enclosing volumes into which only a few well-defined molecules and processes have been incorporated to perform limited specific functions. SPECIFIC AREAS OF OPPORTUNITY Structural Materials Bioinspired processing employs lessons from biology in creating synthetic analog composites. This approach is ideal for designing and fabricating nanostructured organic and organic/inorganic composites by mimicking the processes, structures, and properties of biological materials. Materials like bone, teeth, and shells are simultaneously hard, strong, and tough, with unique hierarchical structural motifs originating at the nanometer scale (Wainwright et al., 1982). The structures of biological composites are hierarchically organized in discrete levels or scales. Virtually all biocomposite systems have at least one distinct structural feature at the molecular, nanoscopic, microscopic, and macroscopic scales. In the case of biological hard materials, nature grows hierarchically structured organic/inorganic composites in which soft materials (e.g., proteins, membranes, and fibers) organized at lengths of 1 to 100 nm are used as frameworks for the growth of specifically oriented and shaped inorganics (e.g., CaCO3, SiO2, Fe3O4, hydroxyapatite) with small unit cells (~1 nm). The high-modulus inorganic phase provides stiffness and the organic phase enhances toughness. Although the principle

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of hierarchical design has already been applied to synthetic composites (Lakes, 1993), techniques to reduce the smallest level of hierarchy to the submicron scale are not complete. Hierarchy at the nanometer scale leads to materials properties fundamentally different from those expected from simple rules for mixing the bulk properties of the constituents (Siegel, 1993). Levels of structural organization are held together by specific interactions between components. For example, the structure of an abalone shell consists of layered plates of CaCO3 (~200 nm) held together by a much thinner (<10 nm) “mortar” of organic template (Figure 7-2). Whatever the nature of the bonding between levels, adequate adhesion is required for the structural integrity of the system. Structurally organized organic surfaces induce growth of specifically oriented, dissimilar constituents catalytically or epitaxially. Highly interacting levels are organized into a hierarchical composite system designed to meet a complex spectrum of functional requirements. As composite systems increase in complexity, they perform better; the so-called intelligent materials and adaptive composite systems result from complex architectural arrangements. A hierarchical biocomposite is more than just a material from which larger objects can be built. It is a complete structural system where nested levels of structural hierarchy appear to yield improved dielectric and mechanical properties for particular functions. The use of molecular biology and genetic engineering to produce materials has focused mainly on health care, resulting in, e.g., a large number of recombinant proteins for human therapeutics. Many of these products have been on the market for years, including insulin, human growth hormone, factor VIII, erythropoietin, and tissue plasminogen activator. Recombinant proteins for human health care have one common feature—high cost. On the other hand, the biological synthesis of functional or structural materials using recombinant DNA technology has not progressed as rapidly as materials for human therapy. One of the main reasons is the lower value added for bioderived materials not targeted to the health care market. It is our belief that there is great potential for using biotechnology to produce biomaterials that could be well suited to DoD needs in 2020. Some of these biomaterials have already been demonstrated to be technically feasible. On the other hand, there are many challenges and barriers to be faced before such biomaterials become realities. In this section, the

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FIGURE 7-2 Mechanical properties of natural and synthetic materials. B4C/Al composites—produced to mimic the interpenetrating and laminated structure of nacre—show significant improvement in properties over single-phase B4C. panel attempts to illustrate with examples as well as state some of the challenges that lie ahead. Armor An area that should be considered is how bioinspired structure might be explored for battlefield armor. For instance, the abalone shell has armor protection capabilities equal to or greater than those of existing materials on a strength-to-weight basis. When laminated hierarchical structures of biological systems (e.g., the nacre of abalone shell) are mimicked in microlaminated ceramic-metal, ceramic-organic, or organic-organic composites, significant improvements in composite mechanical properties are observed (Figure 7-2). Applying a simplified version of this layering to B4C/Al (as well as SiC/Al or B4C/polypropylene) composites significantly increases the mechanical properties. B4C/Al composites are strengthened

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as a result of residual stresses with nanoscale modulations in the interpenetrating network of the ceramic and the metal phases. Greenleaf Corporation at Saegertown, Pennsylvania, has manufactured B4C/Al tiles for use in armor panels aboard C-130 and C-141 gunships. Processing of these ceramic/metal and ceramic/organic microlaminates is based on the concept of infiltrating a laminated scaffolding (e.g., ceramic) with a liquid (e.g., metal or organic polymer). The laminated composites produced by this approach are similar to nacre. However, although these accomplishments attest to the value of transferring lessons from biology and mimicking biological structures to create synthetic analogs, the smallest length scale in a complete system is still in the micron range due to the intrinsic limitation of the tape-casting method employed. On the other hand, the biosynthesis of inorganic biomaterials has not received the same magnitude of research funding as the human health care area. The panel believes that research is necessary to demonstrate the technical and economical feasibilities of such activities. High Performance Fibers—Silk It is well known that the natural product silk is one of the strongest and toughest fibers on a per unit weight basis. Of special importance is that silk performs the same whether it is subject to tensile or compressive forces, a property that differentiates silk from synthetic high-performance fibers. The amino acid sequences of many types of silk are now known. The production of recombinant silks based on parts of these sequences has been demonstrated in bacteria. Many companies and U.S. Army laboratories have conducted R&D on silk, among them Protein Polymer Technologies, Inc., DuPont, and the U.S. Army Natick Laboratories. One of the major hurdles to the commercial development of recombinant silk is its cost. It is difficult today to compete on a cost basis for silk derived from the silk worm versus recombinant protein produced using a bacterial host. Recently, however, Lazaris et al. (2002) have been able to splice the genes for spider silk into cells from a variety of other organisms that, when grown in tissue culture, produce material that can be spun into silk threads. The groups plan to transfer the genes to goats that have been bred to produce the silk in their milk. However, only one of the two proteins of silk has yet been synthesized, and even that one is produced in a form that is shorter and weaker than the natural product. The barrier, as in most other examples discussed here, is biological. We do not yet fully understand the structure of the silk proteins, the mechanism by which the

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spider processes the proteins into fibers, and the techniques required to manipulate the extremely long pieces of DNA that code for the large silk proteins. On the other hand, the integration of recombinant technology with materials science and engineering appears to be a natural partnership to improve the functionalities of recombinant biopolymers like silk over the silk produced naturally (Kaplan, 2002). For example, David Tirrell of the Department of Chemical Engineering at California Institute of Technology has proposed to replace the natural amino acids in native protein polymers using both chemistry and biotechnology to generate such materials with unique added functionalities. New types of polymers with well-defined selectable sequences and uniform composition are possible using these biological production methods. For example, one might see a modified silk with a significant higher strength-to-weight ratio that might be useful as material for the Armed Forces. The generation of highly complex biologically derived structures with new artificial properties and composition is possible. Functional Materials Soft Electronics Recent advances have brought the electron mobilities for organic semiconductors within range of those for amorphous silicon (Heringdorf et al., 2001). This makes organic transistors practicable. Organic LEDs are also on the verge of full commercialization. The core device aspects of these advances are discussed in Chapter 6, but many processing and packaging questions still need to be resolved. DoD applications tend to be more demanding than consumer needs, with greater concern for vibration resistance, redundancy, damage tolerance, and environmental and corrosion resistance. After the battery, much of the weight of portable electronics arises from the need for a rigid shell. Since silicon is inherently brittle and water-sensitive, for instance, there are high costs associated with the rigid packaging it needs for protection from moisture. The material must also be protected from the stresses associated with thermal expansion, acceleration, and vibration. Organic and/or biological electronics, deposited on flexible substrates, promise very considerable savings in weight. By integrating flexible photovoltaic cells, processors, memory, and display

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information is reinserted once a higher level structure has been determined. Similar methods will be needed to design complex fine-scale composites that could mimic biological structure and function. Previous remarks about the need for flexible barrier materials for organic electronics also apply to batteries and fuel cells. Battery casings impose rigidity and are a significant source of weight. Medical Applications Chemical and Biological Warfare Over 20 countries worldwide are developing chemical weapon (CW) capabilities, and at least 10 countries are working actively on biological weapon (BW) agents, and delivery vehicles. CW agents (e.g., phosgene, chlorine, chloropicrin, cholinesterase inhibitors) are relatively cheap and readily obtainable. They may be categorized as blistering agents or toxins against the nervous system, blood, and the respiratory functions. BW agents (bacteria, viruses, ricksettiae, genetically engineered microorganisms) are typically more potent than their CW counterparts, do not require massive stockpiles, are easy to conceal, and are produced with equipment that is commercially available with no legal restriction. Many agents are classified as midspectrum, between chemical and biological: Among them may be toxins from biological sources that adversely regulate pain, sleep, and blood pressure and act as physical and psychological incapacitants. Novel threats emerge from the engineering of biological entities to provide these with additional stability, resistance to antibiotics, or new delivery characteristics, or to make them nondetectable by engineered biosensors or the body’s immune system. Additional threats derive from the release of toxic industrial chemicals (TICs) in the course of conventional warfare, as highlighted in the Yugoslavian theater. The technology of sensors, even against conventional threats, is currently deficient, as highlighted by the experience in the Gulf War, and requires massive materials science and engineering-based advances to meet its C/BW mission.4 Among reported deficiencies are limited standoff and liquid agent detection, potential for high false-alarm rates, weak single-individual biodetection technology, and slow response to central- 4   Johnson-Winegar, A. Keynote address at the First Joint Conference on Point Detection for CBW Defense, Williamsburg, VA, October 23-27, 2000.

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ized coordination. DoD research is directed to devices that will overcome such deficiencies, perhaps hand-held devices usable for detection, identification, quantification, and mapping of battlefield threats, as well as medical diagnosis and monitoring. These are expected to be all-agent capable and reprogrammable for detecting emerging threats. The fundamental scientific and technological advances required to accomplish these lofty objectives were discussed in Opportunities in Biotechnology for Future Army Applications (NRC, 2001), in particular as they relate to sensing and the battlefield environment (Chapter 3). One crucial conclusion emerging from the NRC report is that materials science and materials micro/nanotechnology have played a dominant role in contemporary breakthroughs in the detection and manipulation of biological molecules by way of sensors technology, micro/nanofluidics (e.g., Harrison et al., 1992; Desai et al., 1999), DNA chips (e.g., Christel et al., 1998), and protein chips (e.g., Bashir et al., 2001). It may well be expected that materials science and engineering will be on the forefront of the breakthroughs necessary for adapting and further evolving C/BW applications and civilian protection programs. The 2001 NRC report also addresses biology-based electronics and computing technology (Chapter 4), biologically inspired materials (Chapter 5), biologically inspired solutions for logistics requirements, and novel technologies for the health and performance of warfighters (Chapter 7). Wound Identification and Healing Most battlefield casualties in conventional warfare result from uncontrolled bleeding. It is thus essential to develop methods, and the associated technology platforms, for (1) rapid triaging of battlefield wounds, (2) communication of the results to centralized and distributed battlefield coordination units, (3) summoning and deploying appropriate medical assistance, and (4) delivering medical treatment on-site while waiting for the medics to arrive (the required treatment includes hemostasis, antibacterial intervention, shock therapy, and possible reconstruction of damaged tissue). The NRC (2001) has identified remote triaging of wounds, wound healing, and wounded tissue reconstructive engineering as primary R&D areas. Two of the five highest-priority areas identified pertain centrally to wound identification and treatment: self-replicating systems for wound healing; and shock therapeutics. An Army RFP was recently issued for the establishment of a major nanotechnology center with the primary objective

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of integrating wound triage and treatment technology directly into the warfighters’ uniforms.5 It said: Regardless of the injury mechanism (e.g., infection, trauma, surgery), several critical factors are common to the wound-healing process. These factors include an adequate blood supply to the healing tissue, resolution of associated infections, infiltration of the wound site by inflammatory cells followed by mesenchymal cells, and finally the deposition of neoconnective tissues and epithelial tissues. An adequate blood supply to injured tissue has long been recognized as vital to healing. Cupping, the practice of applying a cup heated by a flame over the site of injury, was used for centuries to ensure blood flow to topical wounds. Today, angiogenic factors can be delivered to the sites of injury to stimulate the formation of new blood vessels. Hyperbaric chambers have been devised to increase oxygen concentration for cells at the site of injury and thereby increase their viability and rate of proliferation. Acupuncture, massage therapy, and a variety of poultices have been used to create the optimal wound-healing environment, especially for recalcitrant nonhealing wounds. Wounds have been categorized by their severity, depth, and chronicity. Each category has its own standards of care. However, the principles of cleanliness, wound covering, tissue apposition, and protection from physical trauma while tissues return to their normal physiologic state apply to all wounds. A variety of coverings are used for acute and chronic wounds. Dressings range from totally occlusive dressings that do not allow fluid (and allow little gas) to pass from the wound to the outer environment, to partially occlusive or nonocclusive dressings that remain permeable to both fluids and gases. Dressings may or may not carry antiseptic or antibiotic compounds. In general, wound coverings for acute traumatic wounds are adequate for treating infections and protecting wounds from further injury. However, there is a pressing need for wound coverings that simultaneously provide, protect, and deliver a stimulus for healing. Stimulation for healing is especially important for large injuries when “space” must be “filled”: In natural healing, large pockets at sites of injury are filled with fluid (usually plasma, blood, or both), which then creates a barrier to rapid healing. Therefore, dressings that not only cover the wound but also 5   Badylak, S.F., Department of Biomedical Engineering, Purdue University, private communication, June 28, 2000 (as cited in NRC, 2001).

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stimulate the formation of new blood vessels and the deposition of connective tissue would greatly improve wound care. Bioerodable polymeric biomaterials specifically designed for biological and mechanical responses in vivo, such as those developed in the laboratories of R. Langer and others (Wise, 2000), provide the basis for these needed improvements but their introduction is hampered by quality issues and cost. There is an inevitable gap between in vitro phenomena that occur under carefully controlled conditions, such as ideal concentrations of growth factors that have predictable effects on selected cell lines, and practical situations that involve the complex of mammalian systems and a plethora of different growth factors (both stimulatory and inhibitory) in environments complicated by infection, tissue necrosis, and external extremes. Although several angiogenic growth factors have been identified, controlling their activity in vivo remains elusive, probably because we lack understanding of the extracellular milieu of growth factors in vivo. Although the sources of growth factors have been identified (e.g., endothelial cells, macrophages, fibroblasts), the mechanisms that stimulate their controlled release and the three-dimensional ultrastructure in which they naturally reside are not well understood. It should therefore not be surprising that growth factors attached to synthetic polymers like polylactic acid and Marlex mesh are not particularly effective. Similarly, bioartificial membranes comprised of selected molecules, such as hyaluronic acid or purified Type I collagen laced with a variety of growth factors, usually fail to produce the desired effect in clinical situations. Many synthetic and natural materials have been investigated for treating wounds in both military and civilian applications (e.g., Germain and Auger, 1995). Among these are wide classes like biodegradable polymers and biomodified materials that slowly release growth factors, blood-clotting agents, angiogenic inductors, or other potentially beneficial molecules. Despite the multitude of approaches and the investment of significant private and public resources, wound healing by material apposition is still far from being achieved. Two types of possible solutions may be envisioned; both require significant advances in materials science and technology. The first solution is better materials, specifically materials that can arrest blood loss, impede infection, counteract shock, and foster biological regeneration. Multiplicity of function would presumably require composite materials, comprising a single or multiple matrix, with interdispersed biological molecules that are released over desired periods of time. The second solution, favored in the

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NRC (2001) report, is to use biological self-replicating systems (e.g., Gentzkow et al., 1996). These systems integrate living cells into synthetic scaffolds for in vitro generation of the desired product (e.g., skin replacement) or even implantation of regenerating bioreactors at the wound site. Major breakthroughs in biomaterials science and engineering are needed to produce scaffolds that allow for such cell/material hybrid bioreactor to perform their desired functions in vivo. Human Performance Enhancement Though any material or technology can be viewed as a human performance enhancement, this review will concentrate on direct modifications to the human body. An example is the use of materials to strengthen the living skeleton. Applying new materials science to the management of human disease would certainly help DoD to maintain the health and readiness for duty of personnel. However, in this section we are considering the role of materials in increasing human performance substantially beyond the optimal native condition of the human body. This panel believes that many operations would have dramatically improved chances for success if nominal body performance is enhanced. Examination of current enhancements/aids to the human body is informative. The enhancements shown in Table 7-2 are all heavily dependent on materials science. Materials science will continue to be critical in further advances, which will also be important for disease management. While a body systems approach might be considered, the panel chose to examine possibilities by functional capability. An advantage of this approach is that optimizing overall performance has to be considered even while trade-offs become apparent. For example, if we want a soldier to be able to run faster, we will have to consider strength to weight in skeletal structure, improved muscle-tendon-bone attachments, improved flexibility and lubrication of moving body parts, changed energy use and waste production, the physical size of the limbs, and the effects on lifespan of body parts and the individual. Table 7-3 considers a reasonable number of functions and points out areas of needed research. Much enabling technology for advances in human performance comes from materials specialists. Such advances include materials for structure and function to create artificial tissues, the ability to manipulate cells and add biochemical groups to them, and advances in microfluidics to allow precision release of physiologic and pharmacologic molecules. Embedded sensor, analog, and logic circuitry (smart materials) will be needed.

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TABLE 7-2 Current Human Enhancements and the Materials Enhancements They Depend On Human Enhancement Technology Materials Enhancement Contact and intraocular lenses Transparency, fluid biocompatibility Hearing aids Ear mold softness, microcircuits, batteries Cochlear prostheses Electrode compatibility Tooth implants Hardness, durability, anchoring Larynx implants Elasticity Silicone implants Biocompatibility, natural feeling Joint and bone replacements Hardness, durability, bone compatibility Artificial blood Membrane permeability, ductility Vascular pumps, implants, and stents Vascular lining, flexibility Renal dialysis Membrane permeability TABLE 7-3 Human Body Functions That Could Potentially Be Enhanced and the Materials Advances Required Body Function Materials Advances Required Locomotion/muscular activity Energy sources for muscles, electronic implants for muscle tone, increased structural integrity for tendons and bone: microfluidics, micromaterial engineering Nervous system control signals Understanding signal transmission and materials improvements for nerves: tissue engineering Energy management Energy uptake, enhanced long-term delivery to tissue, improved waste removal: molecular coatings, enhanced excretion Oxygen management Improved gas exchange for uptake and excretion, artificial blood: surfactant development, tissue surrogates Physical integrity Skin, eye, and mucous membrane protection: tissue integrity, protection from radiation Thermoregulation Heat retention and rejection, energy recycling: smart materials that recognize the external environment Cognition/mental states Energy and toxin management for the central nervous system: drug delivery systems

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To take advantage of the advances in materials technology in the area of human performance, there needs to be an interactive review of the issues and an awareness of the possibilities. Human performance specialists need to provide materials specialists with information on limiting factors. This may require new studies to better define the limitations. For example, physiologists should be able to determine if supranormal walking endurance will be limited by delivery of oxygen and energy or buildup of lactic acid. In a complementary fashion, advanced materials need to be described to physiologists so that they can contemplate how to take advantage of the advances. Human performance enhancement as a new area of work particularly needs an informed multidisciplinary approach. A specific forum must be created to take the specialists beyond their academic disciplines or even the disease mitigation mindset (i.e., research in medicine) and give them the information to be creative. RESEARCH AND DEVELOPMENT PRIORITIES Biology can affect every area of DoD needs of the next several decades. In some areas, i.e., improved battlefield medicine and biological warfare agent identification or interdiction, solutions may be found in specific biological molecules, cells, or systems; in other cases, i.e., smart materials or lightweight structural materials, biology may point the way to improved strategies for material design and synthesis. Where biological molecules or cells are the active component of a device, the challenge to the materials community is not only incorporation of the sensing entity but, perhaps more important, the preservation of biological function in a nonbiological environment. The common theme for all these technologies, research areas, and applications is using biological paradigms to solve problems of materials design, materials synthesis, and system assembly. The panel selected the following research and research management priorities as critical for realizing the opportunities for bioinspired and bioderived materials research for meeting future defense needs. Improving Fundamental Understanding of the Relationships Between Biological Structure, Properties, and Evolution and Materials Design and Synthesis Recent studies of biological systems have clearly shown that large numbers of molecules, structures, and systems in living organisms possess

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attractive materials properties that are beyond the reach of current nonbiological synthetic approaches. Examples are as follows: The natural fabrication processes of hierarchical, systems-oriented biological structures, spanning the size range from nanometers to the macroscopic, lead to impressive and highly desirable performance. The combination of mechanical properties displayed by bone and the instantaneous, highly selective, single-molecule sensitivity of biosensing systems on cell membranes are two examples of the attractive properties and performance of hierarchical, biological systems. Many molecules, structures, systems, and natural fabrication processes have the potential to serve as the basis for materials with enhanced properties for defense applications, either directly adapted or as a pattern for nonbiological mimics. Increasing Communication of DoD Material Needs to Biological and Physical Scientists Progress at the interface between biological and physical scientists is hampered by educational differences and a general lack of communication, especially the lack of communication of DoD materials needs to the biological community. Biology offers a rich source of strategies for solving material problems; conversely, the materials science paradigm offers a systematic methodology for identifying biologically relevant materials. Increasing communication across disciplinary boundaries is likely to produce dramatic benefits to both communities. Basic Research into Biological Molecules, Structures, Systems, and Processes to Lay the Groundwork for Their Use, or Their Use as Models, in Serving the Materials Needs of DoD Fundamental understanding of the relationships between biological structure, properties, and materials synthesis is required if DoD is to take advantage of any new bioinspired or bioderived material. Biological toughening of materials, as exemplified by nacre, tendon, and bone, offers useful models for the next generation of armor/damage-resistant materials. Biological control of primary structure and the resultant enhanced perfor-

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mance, as exemplified by the toughness of dragline silk, is a paradigm for materials by design. Identification and Development of Biocompatible Materials to Enable in Vivo Implantable Devices In vivo detection strategies to identify toxins and pathogens, including masked agents, may enable the detection of a single agent molecule. New materials for implantable, multifunctional, and tissue-interactive devices are required: Emphasis should be placed on materials for the microfluidic movement of biologically active molecules to specific tissues and on materials to interface with electrically active tissues. Development of Packaging Technologies to Preserve the Biological Function of Biologically Enabled Devices Preservation of the biological function of biological molecules is a key driver for the next generation of biologically enabled devices. Because current strategies are inadequate, this area must have high priority. REFERENCES Aizenberg, J., A.J. Black, and G.M. Whitesides. 1998. Controlling local disorder in self-assembled monolayers by patterning the topography of their metallic supports. Nature 394(6696):868-871. Albert, J.T., O.C. Friedrich, H.E. Dechant, and F.G. Barth. 2001. Arthropod touch reception: Spider hair as rapid as touch detectors. J. Comp. Phys. A—Sens. Neural and Beh. Phys. 187(4):303-312. Barth, F.G. 2002. A Spider’s World: Senses and Behavior. Berlin: Springer-Verlag. Bashir, R., R. Gomez, A. Sarikaya, M.R. Ladisch, J. Sturgis, and J.P. Robinson. 2001. Adsorption of avidin on microfabricated surfaces for protein biochip applications. Biotechnology and Bioengineering 73(4):324-328. Chen, T., S.C. Barton, G. Binyamin, Z. Gao, Y. Zhang, H. Kim, and A. Heller. 2001. A miniature biofuel cell. J. Am. Chem. Soc. 123(35):8630-8631. Christel, L.A., K. Petersen, W.A. McMillian, and M.A. Northrup. 1998. Rapid, automated nucleic acid probe assays using silicon microstructures for nucleic acid concentration. Journal of Biomedical Engineering 121(1):22-27. Desai, T.A., D.J. Hansford, L. Kulinsky, A.H. Nashat, G. Rasi, J. Tu, Y. Wang, M. Zhang, and M. Ferrari. 1999. Nanopore technology for biomedical applications. Biomedical Microdevices 2(1):11-40.

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