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NASA NTRS1998

STS-95 Day 04 Highlights

On this forth day of the STS-95 mission, the flight crew, Cmdr. Curtis L. Brown, Pilot Steven W. Lindsey, Mission Specialists Scott E. Parazynski, Stephen K. Robinson, and Pedro Duque, and Payload Specialists Chiaki Mukai and John H. Glenn, are seen performing an evaluation of bone cell activity under microgravity conditions. Glenn then provides blood samples as part of the Protein Turnover Experiment, which is looking at the balance between the building and breakdown of muscle. He also works with the Advanced Organic Separations (ADSEP) experiment, to provides the capability to separate and purify biological materials in microgravity; and with the Microencapsulation Electrostatic Processing System (MEPS), that studies the formation of anti-tumor capsules containing two kinds of drugs.

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NASA NTRS1998

STS-95 Day 08 Highlights

On this eighth day of the STS-95 mission, the flight crew, Cmdr. Curtis L. Brown, Pilot Steven W. Lindsey, Mission Specialists Scott E. Parazynski, Stephen K. Robinson, and Pedro Duque, and Payload Specialists Chiaki Mukai and John H. Glenn, continue to perform microgravity experiments. Specialist John Glenn completes a back-pain questionnaire as part of a study of how the muscle, intervertebral discs and bone marrow change due to microgravity. The results will then be compared with data provided by astronauts during previous missions. Glenn continues blood sample analysis and blood processing that are part of the Protein Turnover (PTO) experiment, which is studying the muscle loss that occurs during space flight.

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NASA NTRS1998

Sensitivity Analysis of Data Link Alternatives for LVLASO

As part of this research, we have modeled the Mode-S system when used to enhance communications among several ground vehicles to facilitate low-visibility landing and surface operations. The model has then been simulated using Bones Designer software. The effectiveness of the model has been evaluated under several conditions: (i) different number of vehicles (100, 200, and 300), (ii) different distributions of interarrival times for squitters: uniform, exponential, and constrained exponential, and (iii) Different safe distances (for collision purpose): squitter length, 1.5*squitter length, and 2* squitter length. The model has been developed in a modular fashion to facilitate any future modifications. The results from the simulations suggest that the Mode S system is indeed capable of functioning satisfactorily even when covering up to 300 vehicles. Certainly, about 10 percent of the squitters undergo collisions and hence the interarrival times for these is much larger than the expected time of 500 msec. In fact, the delay could be as much as 2 seconds. The model could be further enhanced to incorporate more realistic scenarios.

Mukkamala, Ravi↗

NASA NTRS1998

Crew Health and Performance on Mars

The issues surrounding the health and performance on Mars of a human crew are discussed in this presentation. The work of Human Space Life Sciences Program Office (HSLSPO) in the preparation of a crew for a Martian mission is reviewed. This includes a review of issues relating to human health and performance (HHP) in space and microgravity. The Mars design reference mission requires the most rigorous life sciences critical path of any manned mission in the forseeable future. This mission will require a 30 months round trip, with 4 different transistions to different gravities, and two episodes of high gravity load, during the Mars and Earth Aerobraking exercises. A graph is presented which shows the number of subjects with human space flight experience greater than 30 days. A chart presents the physical challenges to HHP in terms of gravity and acceleration and the length of times the crew will be exposed to the various gravity loads. Another chart presents the radiation challenges to the HHP for the duration of the trip. The human element is the most complex element of the mission design. Some challenges (i.e., human engineering and life support) must be overcome, and some issues such as bone loss, and radiation exposure must be addressed prior to making a decision for a manned Martian mission.

Stegemoeller, Charlie↗

NASA NTRS1998

Method for Surface Texturing Titanium Products

The present invention teaches a method of producing a textured surface upon an arbitrarily configured titanium or titanium alloy object for the purpose of improving bonding between the object and other materials such as polymer matrix composites and/or human bone for the direct in-growth of orthopaedic implants. The titanium or titanium alloy object is placed in an electrolytic cell having an ultrasonically agitated solution of sodium chloride therein whereby a pattern of uniform "pock mark" like pores or cavities are produced upon the object's surface. The process is very cost effective compared to other methods of producing rough surfaces on titanium and titanium alloy components. The surface textures produced by the present invention are etched directly into the parent metal at discrete sites separated by areas unaffected by the etching process. Bonding materials to such surface textures on titanium or titanium alloy can thus support a shear load even if adhesion of the bonding material is poor.

Banks, Bruce A.↗

NASA NTRS1999

Changes in Body Inertia During Bed Rest Studies

Development of effective exercise countermeasures is crucial for long duration human space flight. To analyze the mechanical effects of a particular exercise on the musculoskeletal system, the inertial properties of segments of the body must be quantified. Since bone mineral density loss is related to the lack of mechanical stress and strain on the skeletal system, physical analysis can be very useful for countermeasure evaluation.

Todd, Beth A.↗

NASA NTRS1999

Tissue Engineered Skeletal Myofibers can Directly "Sense" Gravitational Force Changes

Long-term manned space flight requires a better understanding of skeletal muscle atrophy resulting from microgravity. Atrophy most likely results from changes at both the systemic level (e.g. decreased circulating growth hormone, increased circulating glucocorticoids) and locally (e.g. decreased myofiber resting tension). Differentiated skeletal myofibers in tissue culture have provided a model system over the last decade for gaining a better understanding of the interactions of exogenous growth factors, endogenous growth factors, and muscle fiber tension in regulating protein turnover rates and muscle cell growth. Tissue engineering these cells into three dimensional bioartificial muscle (BAM) constructs has allowed us to extend their use to Space flight studies for the potential future development of countermeasures. Embryonic avian muscle cells were isolated and BAMs tissue engineered as described previously. The myoblasts proliferate and fuse into aligned postmitotic myofibers after ten to fourteen days in vitro. A cylindrical muscle-like structure containing several thousand myofibers is formed which is approximately 30 mm in length, 2-3 mm in diameter, and attached at each end. For the Space Shuttle experiments, the BAMs were transferred to 55 mL bioreactor cartridges (6 BAMs/cartridge). At Kennedy Space Center, the cartridges were mounted in two Space Tissue Loss (STL) Modules (three to four cartridges per Module) and either maintained as ground controls or loaded in a Mid-Deck locker of the Space Shuttle. The BAM cartridges were continuously perfused during the experiment at 1.5 mL/ min with tissue culture medium. Eighteen BAMs were flown for nine days on Mission STS66 while eighteen BAMs served as ground controls. The complete experiment was repeated on Mission STS77 with twenty four BAMs in each group. BAMs could be maintained in a healthy state for at least 30 days in the perfusion bioreactor cartridges. The BAM muscle fibers directly detected both the loss of gravity and the reloading effects of 1 x g. While total cellular metabolism and total protein degradation rates were not altered during 9 to 10 days in Space, protein synthesis rates were significantly reduced and resulted in significant myofiber atrophy compared to ground controls. One g reloading of the flight muscle cells post-flight significantly increased protein synthesis rates and the synthesis rates of myosin heavy chain, fibronectin, and collagen. Tissue cultured muscle cells can directly "sense" changes in gravity and provide a valid model to begin the study of countermeasures. Based on our ground based experiments, and the experiments of others, growth hormone and/or insulin-like growth factors are attractive protein therapeutics which may assisting attenuating skeletal muscle wasting in space. Our laboratory is developing a new cell-based delivery system for this and other potential therapeutic factors for attenuating muscle and bone wasting.

Vandenburgh, Herman H.↗

NASA NTRS1999

The Effect of Gravity Fields on Cellular Gene Expression

Early theoretical analysis predicted that microgravity effects on the isolated cell would be minuscule at the subcellular level; however, these speculations have not proven true in the real world. Astronauts experience a significant bone and muscle loss in as little as 2 weeks of spaceflight and changes are seen at the cellular level soon after exposure to microgravity. Changes in biological systems may be primarily due to the lack of gravity and the resulting loss of mechanical stress on tissues and cells. Recent ground and flight studies examining the effects of gravity or mechanical stress on cells demonstrate marked changes in gene expression when relatively small changes in mechanical forces or gravity fields were made. Several immediate early genes (IEG) like c-fos and c-myc are induced by mechanical stimulation within minutes. In contrast, several investigators report that the absence of mechanical forces during space flight result in decreased sera response element (SRE) activity and attenuation of expression of IEGs such as c-fos, c-jun and cox-2 mRNAs. Clearly, these early changes in gene expression may have long term consequences on mechanically sensitive cells. In our early studies on STS-56, we reported four major changes in the osteoblast; 1) prostaglandin synthesis in flight, 2) changes in cellular morphology, 3) altered actin cytoskeleton and 4) reduced osteoblast growth after four days exposure to microgravity. Initially, it was believed that changes in fibronectin (FN) RNA, FN protein synthesis or subsequent FN matrix formation might account for the changes in cytoskeleton and/ or reduction of growth. However our recent studies on Biorack (STS-76, STS-81 and STS-84), using ground and in-flight 1-G controls, demonstrated that fibronectin synthesis and matrix formation were normal in microgravity. In addition, in our most recent Biorack paper, our laboratory has documented that relative protein synthesis and mRNA synthesis are not changed after 24 hours exposure to microgravity. We did, however, find significant changes in osteoblast gene expression of IEGs, c-fos and cox-2 in microgravity exposure as compared to ground and in-flight 1-G controls. Subsequent ground studies suggest that the molecular mechanism underlying these changes may involve prostaglandin c-AMP receptors (EPs) and/or subsequent alteration of intracellular signaling in the absence of gravity.

Hughes-Fulford, Millie↗

NASA NTRS1999

Late Pleistocene Interstadial Environment on Faddeyevskiy Island, East-Siberian Sea, Russia

Pollen, plant macrofossil, LOI and radiocarbon analyses of a 1.4-m section from Faddeyevskiy Island, Novosibirskie Ostrova archipelago (75 deg 20 min N, 143 deg 50 min E, 30m elevation) provide new information on the Late Pleistocene interstadial environmental history of this high Arctic region. Bulk radiocarbon dates of 25,700 +/- 1000, 32,780 +/- 500, 35,200 +/- 650 and two AMS dates of 29,950 +/- 660 and 42,990 +/- 1280 indicate that the deposits accumulated during the Kargian (Boutellier) interval. Numerous mammoth (Mammuthus primigenius) remains collected in the vicinity of the site were radiocarbon dated to 36,700-18,500 yr. BP. Rare bison (Bison priscus) bones were dated to 32,200 +/- 600 and 33,100 +/- 320. Poaceae, Cyperaceae, and Artemisia pollen dominate the pollen spectra with some Ranunculaceae, Caryophyllaceae, Rosaceae, and Compositae. These pollen spectra reflect a tundra-steppe vegetation which probably was dominant on the exposed shelf of the Arctic Ocean. The presence of Carex macrofossils infer a summer climate two degrees warmer than today. The productivity of this local vegetation during the Kargian interstadial was apparently high enough to feed the grass-eater herds.

Andreev, Andrei A.↗

NASA NTRS1999

Human Health and Performance Aspects of Mars Design Reference Mission of July, 1997

The human element is the most complex element of the mission design Mars missions will pose significant physiological and psychological challenges to crew members Some challenges (human engineering, life support) must be overcome (potential "non-starters") Some challenges (bone, radiation) may be show-stoppers ISS will only Indirectly address Mars questions before any "Go/No Go" decision Significant amount of ground-based and specialized flight research will be required -- Critical Path Roadmap project will direct HSLSPO's research toward Mars exploration objectives

Charles, John B.↗

NASA NTRS1999

Cardiovascular Session Summary

It was apparent that the bed-rest and spaceflight data indicated that decreases in plasma volume and cardiac atrophy along with cardiac remodeling were fundamental changes which predisposed many astronauts to post flight orthostatic intolerance. Despite the recently acquired in-flight and post-flight muscle sympathetic nerve activity findings suggesting that the sympathetic nerve responses were appropriate there remains significant contrary data from bed-rest studies, post- flight stand tests and hind-limb unweighted rat studies that suggest that the vasoconstrictive responses were compromised at least insufficient in susceptible individuals. The key issues raised is whether a diminished increase in sympathetic activity from baseline without changes in 254 First Biennial Space Biomedical Investigators'Workshop Cardiovascular peak response or receptor adaptations is an abnormal response or is an individual variance of response to the accentuated decrease in stroke volume. Data relating autonomic neural control of heart rate were presented to suggest that the vagal and sympathetic control of heart rate was attenuated. Also, bed-rest and space flight induced attenuated baroreflex control of heart rate was shown to be restored to pre-bedrest function by one bout of maximal dynamic exercise. However, these data were confounded by relying on the use of R-R interval as a measure of efferent responses of the baroreflex during a condition in which the baseline heart rate was changed. Clearly the idea that the autonomic control of heart rate may be changed by microgravity needs further investigation. This direction is suggested despite the fact that in the triple product (HR x SV x TPR = MAP) assessment of the regulation of arterial blood pressure during orthostasis the role of the HR reflex may be less influential than that associated. with cardiac atrophy (SV changes) and aberrant sympathetic vasoconstriction (resistance) changes. Although sympathetic nerve activity responses in-flight and post-flight on neurolab appeared appropriate, enough bed-rest and post-flight stand test data, along with animal model data suggest that vasoconstriction was compromised. The mechanism of this compromised vasoconstriction needs to be delineated. Other major findings concerning microgravity and physiological regulatory systems are that: I . Thermoregulatory adaptation appear to suggest some decrements in the control of cutaneous vasodilation and sweating; 2. Calcium resorption and dietary calcium need to be defined for differing durations of spaceflight, especially as the effects of excess calcium on vasomotor function appears to be detrimental; 3. Neurohumoral mechanisms of microgravity induced changes in neural function and the regulation of plasma volume and total body water, bone resorption and autonomic neural control of the circulation need further delineation; 4. As performance of work tasks become prolonged, the mechanisms of blood pressure regulation in microgravity needs to be used in the recovery period from prolonged work tasks.

Raven, Peter↗

NASA NTRS1999

National Space Biomedical Research Institute

This report summarizes the activities of the National Space Biomedical Research Institute (NSBRI) during FY 1999, the second full year of existence of the NSBRI's research program, and is prepared in accordance with Cooperative Agreement NCC9-58 between NASA's Lyndon B. Johnson Space Center and Baylor College of Medicine (NSBRI). The report consists of progress reports on projects related to the effects of microgravity and space on physiology. The research is broken up in nine areas: (1) Bone loss, (2) Cardiovascular alterations, (3) human performance, (3) immunology, infection and hematology, (4) muscle alterations and atrophy,(5) Neurovestibular adaptation, radiation effects, (6) technology development, and (7) synergy projects.

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NASA NTRS1999

Non-Invasive Assessment of Susceptibility to Ventricular Arrhythmias During Simulated Microgravity

The Cardiovascular Alterations Team is currently conducting studies to determine what alterations in hemodynamic regulation result from sixteen days of simulated microgravity exposure in normal human subjects. In this project we make additional measurements on these same study subjects in order to determine whether there is an increase in susceptibility to ventricular arrhythmias resulting from simulated microgravity exposure. Numerous anecdotal and documented reports from the past 30 years suggest that the incidence of ventricular arrhythmias among astronauts is increased during space flight. For example, documented runs of ventricular tachycardia have been recorded from crew members of Skylab and Mir, there was much attention given by the lay press to Mir Commander Vasily Tslbliyev's complaints of heart rhythm irregularities in July of 1997, and cardiovascular mechanisms may have been causal in the recent death of an experimental primate shortly after return from space. In 1986, a Mir cosmonaut, Alexander Laveikin, was brought home and replaced with an alternate cosmonaut as a result of cardiac dysrhythmias that began during extravehicular activity. Furthermore, at a joint NASA/NSBRI workshop held in January 1998, cardiac arrhythmias were identified as the highest priority cardiovascular risk to a human Mars mission. Despite the evidence for the risk of a potentially lethal arrhythmia resulting from microgravity exposure, the effects of space flight and the associated physiologic stresses on cardiac conduction processes are not known, and an increase in cardiac susceptibility to arrhythmias has never been quantified. In this project, we are determining whether simulated space flight increases the risk of developing life-threatening heart rhythm disturbances such as sustained ventricular tachycardia (defined as ventricular tachycardia lasting at least 30 seconds or resulting in hemodynamic collapse) and ventricular fibrillation. We are obtaining measures of cardiac susceptibility to ventricular arrhythmias in subjects exposed to simulated space flight in the Human Studies Core protocol being conducted by the Cardiovascular Alterations Team, which involves sixteen days .of bed rest. In particular, we are applying a powerful new non-invasive technology, developed in Professor Cohen's laboratory at MIT for the quantitative assessment of the risk of life-threatening ventricular arrhythmias. This technology involves the measurement of microvolt levels of T wave alternans (TWA) during exercise stress, and was recently granted approval by the Food and Drug Administration to be used for the clinical evaluation of patients suspected to be at risk of ventricular arrhythmias. In addition, we are obtaining 24 hour Holter monitoring (to detect non-sustained ventricular tachycardia and to assess heart rate variability). We are also conducting protocols to obtain these same measures on a monthly basis for up to four months in subjects in the Bone Demineralization/calcium Metaboloism Team's long term bed rest study.

Cohen, Richard J.↗

NASA NTRS1999

Instrumentation for Non-Invasive Assessment of Cardiovascular Regulation

It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.

Cohen, Richard J.↗

NASA NTRS1999

Sustained Partial Sleep Deprivation: Effects on Immune Modulation and Growth Factors

The vulnerability to medical emergencies is greatest in space where there are real limits to the availability or effectiveness of ground based assistance. Moreover, astronaut safety and health maintenance will be of increasing importance as we venture out into space for extended periods of time. It is therefore critical to understand the mechanisms of the regulatory physiology of homeostatic systems (sleep, circadian, neuroendocrine, fluid and nutritional balance) and the key roles played in adaptation. This synergy project has combined aims of the "Human Performance Factors, Sleep and Chronobiology Team"; the "Immunology, Infection and Hematology Team"; and the "Muscle Alterations and Atrophy Team", to broadly address the effects of long term sleep reduction, as is frequently encountered in space exploration, on neuroendocrine, neuroimmune and circulating growth factors. Astronaut sleep is frequently curtailed to averages of between 4- 6.5 hours per night. There is evidence that this amount of sleep is inadequate for maintaining optimal daytime functioning. However, there is a lack of information concerning the effects of chronic sleep restriction, or reduction, on regulatory physiology in general, and there have been no controlled studies of the cumulative effects of chronic sleep reduction on neuroendocrine and neuroimmune parameters. This synergy project represents a pilot study designed to characterize the effects of chronic partial sleep deprivation (PSD) on neuroendocrine, neuroimmune and growth factors. This project draws its subjects from two (of 18) conditions of the larger NSBRI project, "Countermeasures to Neurobehavioral Deficits from Cumulative Partial Sleep Deprivation During Space Flight", one of the projects on the "Human Performance Factors, Sleep and Chronobiology Team ". For the purposes of this study, to investigate the effects of chronic sleep loss on neuroendocrine and neuroimmune function, we have focused on the two extreme sleep conditions from this larger study: a 4.2 hour per night condition, and a 8.2 hour per night condition. During space flight, muscle mass and bone density are reduced, apparently due to loss of GH and IGF-I, associated with microgravity. Since >70% of growth hormone (GH) is secreted at night in normal adults, we hypothesized that the chronic sleep restriction to 4 hours per night would reduce GH levels as measured in the periphery. In this synergy project, in collaboration with the "Muscle Alterations and Atrophy Team ", we are measuring insulin-like growth factor-I (IGF-I) in peripheral circulation to test the prediction that it will be reduced by chronic sleep restriction. In addition to stress modulation of immune function, recent research suggests that sleep is also involved. While we all have the common experience of being sleepy when suffering from infection, and being susceptible to infection when not getting enough sleep, the mechanisms involved in this process are not understood and until recently have gone largely overlooked. We believe that the immune function changes seen in spaceflight may also be related to the cumulative effects of sleep loss. Moreover, in space flight, the possibility of compromised immune function or of the reactivation of latent viruses are serious potential hazards for the success of long term missions. Confined living conditions, reduced sleep, altered diet and stress are all factors that may compromise immune function, thereby increasing the risks of developing and transmitting disease. Medical complications, which would not pose serious problems on earth, may be disastrous if they emerged in space.

Mullington, Janet M.↗

NASA NTRS1998

Protein Kinases Possibly Mediate Hypergravity-Induced Changes in F-Actin Expression by Endothelial Cells

Basic cellular functions such as electrolyte concentration, cell growth rate, glucose utilization, bone formation, response to growth stimulation, and exocytosis are modified in microgravity. These studies indicate that microgravity affects a number of physiological systems and included in this are cell signaling mechanisms. Rijken and coworkers performed growth factor studies that showed PKC signaling and actin microfilament organization appears to be sensitive to microgravity, suggesting that the inhibition of signal transduction by microgravity may be related to alterations in actin microfilament organization. However, similar studies have not been done for vascular cells. Vascular endothelial cells play critical roles in providing nutrients to organ and tissues and in wound repair. The major deterrent to ground-based microgravity studies is that it is impossible to achieved true microgravity for longer than a few minutes on earth. Hence, it has not been possible to conduct prolonged microgravity studies except for two models that simulate certain aspects of microgravity. However, hypergravity is quite easily achieved. Several researchers have shown that hypergravity will increase the proliferation of several different cell lines while decreasing cell motility and slowing liver regeneration following partial hepatectomy, These studies indicate the hypergravity also alters the behavior of most cells. Several investigators have shown that hypergravity affects the activation of several protein kinases (PKs) in cells. In this study, we investigated whether hypergravity alters the expression of f-actin by bovine aortic endothelial cells (BAECs) and the role of PK's (calmodulin 11 dependent, PKA and PKC) as mediators of these effects.

Love, Felisha D.↗

NASA NTRS1996

The Physiology of Bed Rest

Prolonged rest in bed has been utilized by physicians and other health-care workers to immobilize and confine patients for rehabilitation and restoration of health since time immemorial. The sitting or horizontal position is sought by the body to relieve the strain of the upright or vertical postures, for example during syncopal situations, bone fractures, muscle injuries, fatigue, and probably also to reduce energy expenditure. Most health-care personnel are aware that adaptive responses occurring during bed rest proceed concomitantly with the healing process; signs and symptoms associated with the former should be differentiated from those of the latter. Not all illnesses and infirmities benefit from prolonged bed rest. Considerations in prescribing bed rest for patients-including duration, body position, mode and duration of exercise, light-dark cycles, temperature, and humidity-have not been investigated adequately. More recently, adaptive physiological responses have been measured in normal, healthy subjects in the horizontal or slightly head-down postures during prolonged bed rest as analogs for the adaptive responses of astronauts exposed to the microgravity environment of outer and bed-rest research.

Fortney, Suzanne M.↗

NASA NTRS2000

NASA's Needs for Biomaterials within the HEDS Initiative

The part to be played by materials scientists to further NASA's exploration missions cannot be underestimated. To quote Jerome Groopman (New Yorker, February 14, 2000), "The rocket science will be the easy part". The four main risks on the Critical Path Road Map during a three-year sojourn to Mars are osteoporosis, psychological problems, radiation induced cancer and acute medical trauma. NASA's microgravity materials science program has investigations in membrane fabrication, bone growth and materials for radiation protection. These programs will be reviewed in the context of the four main risks, as will other potential uses of biomaterials and applications of biomimetic processing.

Gillies, Donald C.↗