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NASA NTRS1991

Skeletal responses to spaceflight

The role of gravity in the determination of bone structure is elucidated by observations in adult humans and juvenile animals during spaceflight. The primary response of bone tissue to microgravity is at the interface of the mineral and matrix in the process of biomineralization. This response is manifested by demineralization or retarded growth in some regions of the skeleton and hypermineralization in others. The most pronounced effects are seen in the heelbone and skull, the most distally located bones relative to the heart. Ground based flight simulation models that focus on changes in bone structure at the molecular, organ, and whole body levels are described and compared to flight results. On Earth, the morphologic and compositional changes in the unloaded bones are very similar to changes during flight; however, the ground based changes appear to be more transient. In addition, a redistribution of bone mineral in gravity-dependent bones occurs both in space and during head down positioning on Earth. Longitudinal data provided considerable information on the influence of endocrine and muscular changes on bone structure after unloading.

Morey-Holton, Emily↗

NASA NTRS1992

Neurology of microgravity and space travel

Exposure to microgravity and space travel produce several neurologic changes, including SAS, ataxia, postural disturbances, perceptual illusions, neuromuscular weakness, and fatigue. Inflight SAS, perceptual illusions, and ocular changes are of more importance. After landing, however, ataxia, perceptual illusions, neuromuscular weakness, and fatigue play greater roles in astronaut health and readaptation to a terrestrial environment. Cardiovascular adjustments to microgravity, bone demineralization, and possible decompression sickness and excessive radiation exposure contribute further to medical problems of astronauts in space. A better understanding of the mechanisms by which microgravity adversely affects the nervous system and more effective treatments will provide healthier, happier, and longer stays in space on the space station Freedom and during the mission to Mars.

Fujii, M. D.↗

NASA NTRS1993

Endocrine and metabolic changes in payload specialist (L-1)

The endocrine system plays an important role in the adaptation to unusual environments by secreting hormones to control metabolism. Since human beings have long evolved on the surface of the Earth under a gravity environment, the weightless environment must be quite unusual for them. The purpose of this experiment is to study the mechanisms of human adaptation to a weightless environment from endocrine and metabolic changes. Our study plan is focused on four major physiological changes which were reported during past space flights or which may be expected to occur under that condition: (1) hormone and metabolic changes associated with fluid shift; (2) bone demineralization and muscle atrophy; (3) altered circadian rhythm; and (4) stress reaction during space flight.

Matsui, Nobuo↗

NASA NTRS1995

Characterization of microgravity effects on bone structure and strength using fractal analysis

The effect of micro-gravity on the musculoskeletal system has been well studied. Significant changes in bone and muscle have been shown after long term space flight. Similar changes have been demonstrated due to bed rest. Bone demineralization is particularly profound in weight bearing bones. Much of the current techniques to monitor bone condition use bone mass measurements. However, bone mass measurements are not reliable to distinguish Osteoporotic and Normal subjects. It has been shown that the overlap between normals and osteoporosis is found for all of the bone mass measurement technologies: single and dual photon absorptiometry, quantitative computed tomography and direct measurement of bone area/volume on biopsy as well as radiogrammetry. A similar discordance is noted in the fact that it has not been regularly possible to find the expected correlation between severity of osteoporosis and degree of bone loss. Structural parameters such as trabecular connectivity have been proposed as features for assessing bone conditions. In this report, we use fractal analysis to characterize bone structure. We show that the fractal dimension computed with MRI images and X-Ray images of the patella are the same. Preliminary experimental results show that the fractal dimension computed from MRI images of vertebrae of human subjects before bedrest is higher than during bedrest.

Acharya, Raj S.↗

NASA NTRS1997

The Role of GH/IGF-I Axis in Muscle Homeostasis During Weightlessness

Exposure to reduced gravity during space travel profoundly alters the loads placed on bone and muscle. Astronauts suffer significant losses of muscle and bone strength during weightlessness. Exercise as a countermeasure is only partially effective in remedying severe muscle atrophy and bone demineralization. Similar wasting of muscles and bones affects people on Earth during prolonged bed rest or immobilization due to injury. In the absence of weight bearing activity, atrophy occurs primarily in the muscles that act in low power, routine movements and in maintaining posture. Hormonal disfunction could contribute in part to the loss of muscle and bone during spaceflight. Reduced levels of human Growth Hormone (hGH) were found in astronauts during space flight, as well as reduced GH secretory activity was observed from the anterior pituitary in 7-day space flight rats. Growth hormone has been shown to be required for maintenance of muscle mass and bone mineralization, in part by mediating the biosynthesis IGF-I, a small polypeptide growth factor. IGF biosynthesis and secretion plays an important role in potentiating muscle cell differentiation and has been shown to drive the expression of myogenin, a myogenic specific basic helix-loop-helix factor. IGF-I has also been shown to have an important role in potentiating muscle regeneration, repair and adult muscle hypertrophy.

Schwartz, Robert J.↗

NASA NTRS1999

Computer Aided Modeling to Determine the Effectiveness of Resistive Exercises as Countermeasures for Bone Mineral Density Loss

Due to the loss of gravitational loading, astronauts have a tendency to lose bone mineral density in their lumbar spine and lower extremities on orbit. NASA requires astronauts to perform exercises during space flight to help reduce the amount of demineralization. To test these exercises on earth, 17 week bed rest studies are conducted that consist of specific diet and exercise regimes. Developing a finite element model of these exercises will help to quantify the stress distribution imposed by of each of these exercises. To help develop this model, MRI images are acquired from individuals participating in the bed rest studies. The MRIs can be used to create a subject specific model of each individual for testing. The MRIs are processed in the Magnetic Resonance Imaging Data Transfer System program to develop a three-dimensional finite element model of the femur for evaluation. Modifications were made to the MRIDTS that simplified the model creation process. These modifications made it possible to construct two separate models of different portions of a bone simultaneously and then later connect them manually. This helped alleviate the warping problem associated with the drastic changes in geometry found in some body parts, such as the joints. The code was also modified to incorporate material properties of various bone components into the model. Interior meshing was also incorporated into the program to allow for both the cortical shell and the entire bone to be modeled. A prototype model of the right femur of an adult female is being constructed and tested to determine the feasibility of finite element analysis as a tool for evaluating exercise effectiveness. The model is being run through the ANSYS finite element program on the Alabama Super Computer Network. After the model is validated, models of bedrest subjects can be generated to investigate exercise countermeasures.

Murphy, Benjamin M.↗

NASA NTRS1997

Extraterrestrial Helium (He@C60) Trapped in Fullerenes in the Sudbury Impact Structure

Fullerenes (C60 and C70) have recently been identified in a shock-produced breccia (Onaping Formation) associated with the 1.85-Ga Sudbury Impact Crater. The presence of parts-per-million levels of fullerenes in this impact structure raises interesting questions about the processes that led to the formation of fullerenes and the potential for delivery of intact organic material to the Earth by a large bolide (e.g., asteroid or comet). Two possible scenarios for the presence of fullerenes in the Sudbury impact deposits are that (1) fullerenes are synthesized within the impact plume from the C contained in the bolide; or (2) fullerenes are already present in the bolide and survived the impact event. The correlation of C and trapped noble gas atoms in meteorites is well established. Primitive meteorites contain several trapped noble gas components that have anomalous isotopic compositions, some of which may have a presolar origin. Several C-bearing phases, including SiC, graphite, and diamond, have been recognized as carriers of trapped noble gases. It has also been suggested that fullerenes (C60 and C70) might be a carrier of noble gas components in carbonaceous chondrites. Recently, fullerenes have been detected in separate samples in the Allende meteorite. Carbon-60 is large enough to enclose the noble gases He, Ne, Ar, Kr, and Xe, but it is too small to contain diatomic gases such as N2 or triatomic gases such as CO2. Recent experimental work has demonstrated that noble gases of a specific isotopic composition can be introduced into synthetic fullerenes at high temperatures and pressures; these encapsulated gases can then be released by the breaking of one or more C bonds during step-heating under vacuum. These thermal-release patterns for He encapsulated within the C60 molecule (He@C60) are similar to the patterns for acid residues of carbonaceous chondrites, suggesting that fullerenes could be an additional carrier of trapped noble gases in acid residues of meteorites. Analysis and Results: In order to characterize the noble gas compositions of the Sudbury fullerenes, we undertook a systematic study of acid-resistant residues throughout the C-rich layer (Black member) of the Onaping Formation. Samples were demineralized and extracted using standard techniques. The Onaping extracts were analyzed using several techniques, including UV-Vis adsorption, electro spray mass spectrometry, and laser desorption (linear and reflectron) time-of-flight (TOF) mass spectrometry (LDMS). The Sudbury fullerenes were then separated and purified using HPLC coupled with a photo diode array detector. The HPLC extracts containing the purified fullerenes were loaded into a metal tube furnace within a glove box under a N atmosphere in preparation for noble gas analyses. The 3-He and 4-He content of the fullerene extracts was measured using previously reported standard techniques . Discussion: Fullerenes (C60 and C70) in the Sudbury Impact Structure have been found to contain trapped He with a 3-He/4-He ratio greater than 5 x 10(exp -4). The 3-He/4-He ratio exceeds the accepted solar value by more than 30% and is more than 10x higher than the maximum reported mantle value. Terrestrial nuclear reactions or cosmic-my bombardment are not sufficient to generate such a high ratio. The 3-He/4-He ratios in the Sudbury fullerenes are similar to those determined for interplanetary dust particles. The greater-than-solar ratios of 3-He/4-He in the Sudbury fullerenes may indicate a presolar origin, although alternative mechanisms occurring in the ISM to explain these high ratios (e.g., spallation reactions, selective He implantation, etc.) cannot be entirely ruled out. We are currently attempting to isolate enough fullerene material to measure anomalous Ne (or Kr or Xe) contained within the C60 (e.g., the "pure" 22-Ne component) and thus determine whether the Sudbury fullerenes are indeed presolar in origin.

Becker, L.↗

NASA NTRS1997

New Potential Sources for Black Onaping Carbon

One intriguing and important issue of the Sudbury Structure concerns the source of the relatively large amount of C in the Onaping Formation Black member. This dilemma was recently addressed, and the conclusion was reached that an impactor could not have delivered all of the requisite C. Becker et al. have suggested that much of the C came from the impactor and reported the presence of interstellar He "caged" inside some fullerenes that may have survived the impact. So, conceivably, the C inventory in the Sudbury Structure comes from both target and impactor materials, although the known target rocks have little C. We discuss here the possibility of two terrestrial sources for at least some of the C: (1) impact evaporation/dissociation of C from carbonate target rocks and (2) the presence of heretofore-unrecognized C-rich (up to 26 wt%) siliceous "shale," fragments, which are found in the upper, reworked Black member. Experimental: Hypervelocity impact of a 0.635-diameter Al projectile into dolomite at 5.03 km/s (performed at the Ames Research Center vertical gun range) produced a thin, black layer (= 0.05 mm thick) that partially lined the crater and coated impactor remnants. Scanning electronic microscope (SEM) imagery shows this layer to be spongelike on a submicron scale and Auger spectroscopic analyses yield: 33% C, 22% Mg, 19% 0, and 9% Al (from the projectile). Elemental mapping shows that all of the available 0 is combined with Ca and Mg, Al is not oxidized, and C is in elemental form. Dissociation efficiency of C from CO2 is estimated to be <10% of crater volume. Raman spectroscopy indicates that the C is highly disorganized graphite. Another impact experiment [4] also produced highly disordered graphite from a limestone target (reducing collector), in addition to small amounts of diamond/lonsdaleite/chaoite (oxidizing collector). These experiments confirm the reduction of C from carbonates in impact vapor plumes. Observational: SEM observations and microprobe analyses of small, black shalelike inclusions in the upper Black Onaping indicate high C contents (7-26 wt% avg. = 16%). They contain mostly quartz and carbonaceous matter with small amounts of altered K-feldspar, clays, Fe oxide, and a sulfide. No evidence of shock is seen in quartz, and overall characteristics indicate a natural, lightly metamorphosed carbonaceous shale or mudstone that probably existed as a preimpact rock in the target region and distal fragments washed in during early crater filling. Fragments range in size from tens of microns to cm and increase in abundance in the upper Black toward the Onwatin contact, although their distribution is highly irregular. This increase corresponds to an increase in "organic" C with increasingly negative delta-13 C values and S, together with a decrease in fullerene abundance. In addition, we have found soot in acid-demineralized residues of the Onwatin but not in the Onaping samples. These data could be consistent with impact plume and atmospheric chemical processes, with possible diageneric ovedays. We are analyzing carbonaceous fractions of the Onaping and Onwatin to determine diagnostic C isotopic signatures Analyses by Whitehead et al. on bulk samples revealed no definitive source or processes, although delta-13 C values for "organic" C overlapped those for some meteorites. Discussion: If impact evaporation of Sudbury target carbonates did occur, then where are the carbonates? Distal carbonate (limestone/dolostone) exposures of the Espanola Formation (Huronian Supergroup) are generally thin-bedded, although remnants that partially encompass the Sudbury Crater are variable in thickness and may locally reach 250 m . If a carbonate thickness of 100-200 in existed at the target site, then copious amounts of C could have been reduced by impact processing of carbonates and also C-shale, depending on the efficiency of the processing and the amount of postimpact oxidation. Conclusion: The Sudbury crater offers a unique opportunity to study preserved characteristics of immediate carbonaceous fallback matter and particles of short-term residency in the impact plume as well as dust/aerosols from postimpact atmospheric processing.

Bunch, T. E.↗

NASA NTRS1997

A Biomechanical Comparison of 1-G and Fully-Loaded Simulated Zero-Gravity Locomotion

Exercise will almost certainly play an integral part in minimizing the bone mineral loss and muscular atrophy that occur during spaceflight. It has been hypothesized that an effective exercise regimen can be developed to elicit loads on the lower extremities and require muscle actions which resemble those encountered on Earth. The Penn State Zero-Gravity Simulator (PSZS) is a device which suspends subjects horizontally from multiple latex cords, with each cord negating the weight of a limb segment. A treadmill mounted on the wall under the PSZS enables subjects to run in simulated 0G. Subjects wear a harness to which a number of springs, which provide a gravity replacement load, are connected. The opposite end of each spring is connected to the side of the treadmill. During exercise, astronauts currently wear a similar harness in which the spring tethering load pulls at both the waist and shoulders. Ground reaction forces, muscular activations, and joint angles of the left leg during overground, treadmill, and fully-loaded zero-gravity simulated (ZLS) locomotion were assessed in order to gain insight into the effectiveness of the exercise regimen used by NASA to prevent the muscular atrophy and bone demineralization which occur in weightlessness. There were three hypotheses to this research. It was hypothesized that there will be no differences in peak ground reaction forces and peak loading rates between overground gait and gait in the full body weight loaded conditions in the ZLS. A second hypothesis was that that there will be no differences in hip, knee, and ankle joint positions between walking or running overground, on a standard treadmill, and in full bodyweight loaded conditions in the ZLS. The third hypothesis was that the muscular activations, as a percentage of maximal voluntary contraction, will be similar between walking or running overground, on a standard treadmill, and in full body-weight loaded conditions in the ZLS.

McCrory, Jean L.↗

NASA NTRS2001

Spectroscopic characterization of collagen cross-links in bone

Collagen is the most abundant protein of the organic matrix in mineralizing tissues. One of its most critical properties is its cross-linking pattern. The intermolecular cross-linking provides the fibrillar matrices with mechanical properties such as tensile strength and viscoelasticity. In this study, Fourier transform infrared (FTIR) spectroscopy and FTIR imaging (FTIRI) analyses were performed in a series of biochemically characterized samples including purified collagen cross-linked peptides, demineralized bovine bone collagen from animals of different ages, collagen from vitamin B6-deficient chick homogenized bone and their age- and sex-matched controls, and histologically stained thin sections from normal human iliac crest biopsy specimens. One region of the FTIR spectrum of particular interest (the amide I spectral region) was resolved into its underlying components. Of these components, the relative percent area ratio of two subbands at approximately 1660 cm(-1) and approximately 1690 cm(-1) was related to collagen cross-links that are abundant in mineralized tissues (i.e., pyridinoline [Pyr] and dehydrodihydroxylysinonorleucine [deH-DHLNL]). This study shows that it is feasible to monitor Pyr and DHLNL collagen cross-links spatial distribution in mineralized tissues. The spectroscopic parameter established in this study may be used in FTIRI analyses, thus enabling the calculation of relative Pyr/DHLNL amounts in thin (approximately 5 microm) calcified tissue sections with a spatial resolution of approximately 7 microm.

Non-NASA Center↗

NASA NTRS1986

Statolith formation in Cnidaria: effects of cadmium on Aurelia statoliths

Statolith formation in Cnidaria was reviewed with an emphasis on Aurelia statoliths. The review provides information on the chemical composition, mechanisms of initiation of mineralization, and effects of environmental factors on Cnidarian statolith formation. Environmental factors discussed included modified sea water ingredients, X-irradiation, clinostat rotation, and petroleum oil ingredients. A detailed account of the effects of cadmium on mineralization and demineralization of Aurelia statoliths is given. Cadmium at dosages of 2 to 4 micromoles significantly reduces statolith numbers in developing ephyrae. At a dosage of 3 micromoles, cadmium accelerates statolith loss in unfed ephyrae studied at 4 and 8 days following ephyrae release from strobilae. Cadmium, therefore, is shown to reduce statolith numbers in developing ephyrae and to cause greater reduction of statolith numbers in unfed ephyrae after 4 and 8 days than occurred in controls. Supplementation of Cd(2+)-containing artificial sea water (ASW) with calcium (3X and 5X ASW calcium content) results in higher numbers of statoliths at day 4 as compared with cadmium-treated ephyrae. At 8 days only the 5X calcium supplemented ASW is effective in enhancing statolith numbers in Cd(2+)-treated ephyrae. These results suggest that cadmium competes in some manner with calcium at the mineralizing sites of Aurelia.

NASA Discipline Number 40-10↗

NASA NTRS1988

Vestibular factors influencing the biomedical support of humans in space

This paper will describe the biomedical support aspects of humans in space with respect to the vestibular system. The vestibular system is thought to be the primary sensory system involved in the short-term effects of space motion sickness although there is increasing evidence that many factors play a role in this complex set of symptoms. There is the possibility that an individual's inner sense of orientation may be strongly coupled with the susceptibility to space motion sickness. A variety of suggested countermeasures for space motion sickness will be described. Although there are no known ground-based tests that can predict space motion sickness, the search should go on. The long term effects of the vestibular system in weightlessness are still relatively unknown. Some preliminary data has shown that the otoconia are irregular in size and distribution following extended periods of weightlessness. The ramifications of this data are not yet known and because the data was obtained on lower order animals, definitive studies and results must wait until the space station era when higher primates can be studied for long durations. This leads us to artificial gravity, the last topic of this paper. The vestibular system is intimately tied to this question since it has been shown on Earth that exposure to a slow rotating room causes motion sickness for some period of time before adaptation occurs. If the artificial gravity is intermittent, will this mean that people will get sick every time they experience it? The data from many astronauts returning to Earth indicates that a variety of sensory illusions are present, especially immediately upon return to a 1-g environment. Oscillopsia or apparent motion of the visual surround upon head motion along with inappropriate eye motions for a given head motion, all indicate that there is much to be studied yet about the vestibular and CNS systems reaction to a sudden application of a steady state acceleration field like 1-g. From the above information it is obvious that the vestibular system does have unique requirements when it comes to the biomedical support of space flight. This is not to say that other areas such as cardiovascular, musculo-skeletal, immunological and hematological systems do not have their own unique requirements but that possible solutions to one system can provide continuing problems to another system. For example, artificial gravity might be helpful for long term stabilization of bone demineralization or cardiovascular deconditioning but might introduce a new set of problems in orientation, vestibular conflict and just plain body motion in a rotating space vehicle.

Non-NASA Center↗

NASA NTRS2000

Artificial gravity as a countermeasure in long-duration space flight

Long-duration exposure to weightlessness results in bone demineralization, muscle atrophy, cardiovascular deconditioning, altered sensory-motor control, and central nervous system reorganizations. Exercise countermeasures and body loading methods so far employed have failed to prevent these changes. A human mission to Mars might last 2 or 3 years and without effective countermeasures could result in dangerous levels of bone and muscle loss. Artificial gravity generated by rotation of an entire space vehicle or of an inner chamber could be used to prevent structural changes. Some of the physical characteristics of rotating environments are outlined along with their implications for human performance. Artificial gravity is the centripetal force generated in a rotating vehicle and is proportional to the product of the square of angular velocity and the radius of rotation. Thus, for a particular g-level, there is a tradeoff between velocity of rotation and radius. Increased radius is vastly more expensive to achieve than velocity, so it is important to know the highest rotation rates to which humans can adapt. Early studies suggested that 3 rpm might be the upper limit because movement control and orientation were disrupted at higher velocities and motion sickness and chronic fatigue were persistent problems. Recent studies, however, are showing that, if the terminal velocity is achieved over a series of gradual steps and many body movements are made at each dwell velocity, then full adaptation of head, arm, and leg movements is possible. Rotation rates as high as 7.5-10 rpm are likely feasible. An important feature of the new studies is that they provide compelling evidence that equilibrium point theories of movement control are inadequate. The central principles of equilibrium point theories lead to the equifinality prediction, which is violated by movements made in rotating reference frames. Copyright 2000 Wiley-Liss, Inc.

Review Literature↗

NASA NTRS1999

Effects of microgravity on urinary osteopontin

Increased risk of renal stone formation during space flight has been linked primarily to increased calcium excretion from bone demineralization induced by space flight. Other factors contributing to increased risk include increased urinary calcium oxalate supersaturation, while urinary citrate, magnesium and volume are all decreased. The aim of this study was to increase the predictive value of stone risk profiles for crew members during space flight by evaluating the excretion of urinary protein inhibitors of calcium crystallization so that more comprehensive stone risk profiles could relate mineral saturation to the concentrations of inhibitor proteins. Levels of urinary osteopontin (uropontin) are reported in a series of 14 astronauts studied before, during, and after space flights. During space flight, a compensatory increase in uropontin excretion was not observed. However, the uropontin excretion of a majority of astronauts was increased during the period after space flight and was maximal at 2 wk after landing. The downward shift in the molecular size of uropontin observed in samples obtained during space flight was shown to result from storage at ambient temperature during flight, rather than an effect of microgravity on uropontin synthesis.

NASA Experiment Number 9401651↗

NASA NTRS1997

Angiogenesis and osteogenesis in an orthopedically expanded suture

The purpose of this study was to examine the angiogenic and the subsequent osteogenic responses during a 96-hour time-course after sutural expansion. Fifty rats were divided into: (1) a control group that received only angiogenic induction through injection of 5 ng/gm recombinant human endothelial cell growth factor (rhECGF); (2) an experimental group that received orthopedic expansion and rhECGF; (3) a sham group that received expansion and sodium chloride (NaCl) injection; and (4) a baseline group that received no expansion or injection. All rats were injected with 3H-thymidine (1.0 microCi/gm) 1 hour before death to label the DNA of S-phase cells. Demineralized sections (4 microm thick) were stained with hematoxylin and eosin. Angiogenesis and cell migration were analyzed with a previously established cell kinetics model. Analysis of variance was used to test the hypothesis that enhancement of angiogenesis stimulates reestablishment of osteogenic capability. Blood vessel number, area, and endothelial cell-labeled index significantly increased in experimental groups, but no difference was found between control and baseline groups. Labeled-pericyte index and activated pericyte numbers in the experimental group were also higher than in the sham groups. These results show that supplemental rhECGF enhances angiogenesis in expanded sutures but not in nonexpanded sutures. Data also suggest that pericytes are the source of osteoblasts in an orthopedically expanded suture.

NASA Discipline Musculoskeletal↗

NASA NTRS1993

Utilization of microgravity bioreactors for differentiation of mammalian skeletal tissue

Bioreactor cell and tissue culture vessels can be used to study bone development in a simulated microgravity environment. These vessels will also provide an advantageous, low maintenance culture system on space station Freedom. Although many types of cells and tissues can potentially utilize this system, our particular interest is in developing bone tissue. We have characterized an organ culture system utilizing embryonic mouse pre-metatarsal mesenchyme, documenting morphogenesis and differentiation as cartilage rods are formed, with subsequent terminal chondrocyte differentiation to hypertrophied cells. Further development to form bone tissue is achieved by supplementation of the culture medium. Research using pre-metatarsal tissue, combined with the bioreactor culture hardware, could give insight into the advantages and/or disadvantages of conditions experienced in microgravity. Studies such as these have the potential to enhance understanding of bone development and adult bone physiology, and may help define the processes of bone demineralization experienced in space and in pathological conditions here on earth.

Non-NASA Center↗

NASA NTRS2001

Bioengineered anterior cruciate ligament

The present invention provides a method for producing an anterior cruciate ligament ex vivo. The method comprises seeding pluripotent stem cells in a three dimensional matrix, anchoring the seeded matrix by attachment to two anchors, and culturing the cells within the matrix under conditions appropriate for cell growth and regeneration, while subjecting the matrix to one or more mechanical forces via movement of one or both of the attached anchors. Bone marrow stromal cells are preferably used as the pluripotent cells in the method. Suitable matrix materials are materials to which cells can adhere, such as a gel made from collagen type I. Suitable anchor materials are materials to which the matrix can attach, such as Goinopra coral and also demineralized bone. Optimally, the mechanical forces to which the matrix is subjected mimic mechanical stimuli experienced by an anterior cruciate ligament in vivo. This is accomplished by delivering the appropriate combination of tension, compression, torsion, and shear, to the matrix. The bioengineered ligament which is produced by this method is characterized by a cellular orientation and/or matrix crimp pattern in the direction of the applied mechanical forces, and also by the production of collagen type I, collagen type III, and fibronectin proteins along the axis of mechanical load produced by the mechanical forces. Optimally, the ligament produced has fiber bundles which are arranged into a helical organization. The method for producing an anterior cruciate ligament can be adapted to produce a wide range of tissue types ex vivo by adapting the anchor size and attachment sites to reflect the size of the specific type of tissue to be produced, and also adapting the specific combination of forces applied, to mimic the mechanical stimuli experienced in vivo by the specific type of tissue to be produced. The methods of the present invention can be further modified to incorporate other stimuli experienced in vivo by the particular developing tissue, some examples of the stimuli being chemical stimuli, and electro-magnetic stimuli. Some examples of tissue which can be produced include other ligaments in the body (hand, wrist, elbow, knee), tendon, cartilage, bone, muscle, and blood vessels.

Altman, Gregory↗

NASA NTRS2006

Space Life Sciences at NASA: Spaceflight Health Policy and Standards

In January 2005, the President proposed a new initiative, the Vision for Space Exploration. To accomplish the goals within the vision for space exploration, physicians and researchers at Johnson Space Center are establishing spaceflight health standards. These standards include fitness for duty criteria (FFD), permissible exposure limits (PELs), and permissible outcome limits (POLs). POLs delineate an acceptable maximum decrement or change in a physiological or behavioral parameter, as the result of exposure to the space environment. For example cardiovascular fitness for duty standards might be a measurable clinical parameter minimum that allows successful performance of all required duties. An example of a permissible exposure limit for radiation might be the quantifiable limit of exposure over a given length of time (e.g. life time radiation exposure). An example of a permissible outcome limit might be the length of microgravity exposure that would minimize bone loss. The purpose of spaceflight health standards is to promote operational and vehicle design requirements, aid in medical decision making during space missions, and guide the development of countermeasures. Standards will be based on scientific and clinical evidence including research findings, lessons learned from previous space missions, studies conducted in space analog environments, current standards of medical practices, risk management data, and expert recommendations. To focus the research community on the needs for exploration missions, NASA has developed the Bioastronautics Roadmap. The Bioastronautics Roadmap, NASA's approach to identification of risks to human space flight, revised baseline was released in February 2005. This document was reviewed by the Institute of Medicine in November 2004 and the final report was received in October 2005. The roadmap defines the most important research and operational needs that will be used to set policy, standards (define acceptable risk), and implement an overall Risk Management and Analysis process. Currently NASA is drafting spaceflight health standards for neurosensory alterations, space radiation exposure, behavioral health, muscle atrophy, cardiovascular fitness, immunological compromise, bone demineralization, and nutrition.

Davis, Jeffrey R.↗