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NASA NTRS1980

Certain problems of space biotechnology

Experiments in the field of biotechnology conducted by the USA Apollo and Skylab space probes are described, as well as the joint Soviet-American Apollo-Soyuz Test Project (ASTP). Experiments in electrophoretic separation in space of biological compounds in a liquid medium are detailed. Space processing of vaccines and separation of human and animal cells are described. Methyl-cellulose, a coating for use in electrophoresis was developed. Erythropoietin, which stimulates the formation of red blood corpuscles in bone marrow, was obtained in pure form.

Gilyarov, V. N.↗

NASA NTRS1994

Quantification of Daily Physical Activity

The influence of physical activity on the maintenance and adaptation of musculoskeletal tissue is difficult to assess. Cumulative musculoskeletal loading is hard to quantify and the attributes of the daily tissue loading history affecting bone metabolism have not been completely identified. By monitoring the vertical component of the daily ground reaction force (GRFz), we have an indirect measure of cumulative daily lower limb musculoskeletal loading to correlate with bone density and structure. The objective of this research is to develop instrumentation and methods of analysis to quantify activity level in terms of the daily history of ground reaction forces.

Whalen, Robert↗

NASA NTRS2018

High-precision Method for Cyclic Loading of Small-Animal Vertebrae to Assess Bone Quality

One potentially important bone quality characteristic is the response of bone to cyclic (repetitive) mechanical loading. In small animals, such as in rats and mice, cyclic loading experiments are particularly challenging to perform in a precise manner due to the small size of the bones and difficult-to-eliminate machine compliance. Addressing this issue, we developed a precise method for ex vivo cyclic compressive loading of isolated mouse vertebral bodies. The method has three key characteristics: 3D-printed support jigs for machining plano-parallel surfaces of the tiny vertebrae; pivotable loading platens to ensure uniform contact and loading of specimen surfaces; and specimen-specific micro-CT-based finite element analysis to measure stiffness to prescribe force levels that produce the same specified level of strain for all test specimens. To demonstrate utility, we measured fatigue life for three groups (n = 5-6 per group) of L5 vertebrae of C57BL/6J male mice, comparing our new method against two methods commonly used in the literature. We found reduced scatter of the mechanical behavior for this new method compared to the literature methods. In particular, for a controlled level of strain, the standard deviation of the measured fatigue life was up to 5-fold lower for the new method (F-ratio = 4.9; p < 0.01). The improved precision for this new method for biomechanical testing of small-animal vertebrae may help elucidate aspects of bone quality.

Bone quality↗

NASA NTRS2003

Issues of exploration: human health and wellbeing during a mission to Mars

Today, the tools are in our hands to enable us to travel away from our home planet and become citizens of the solar system. Even now, we are seriously beginning to develop the robust infrastructure that will make the 21st century the Century of Space Travel. But this bold step must be taken with due concern for the health, safety and wellbeing of future space explorers. Our long experience with space biomedical research convinces us that, if we are to deal effectively with the medical and biomedical issues of exploration, then dramatic and bold steps are also necessary in this field. We can no longer treat the human body as if it were composed of muscles, bones, heart and brain acting independently. Instead, we must lead the effort to develop a fully integrated view of the body, with all parts connected and fully interacting in a realistic way. This paper will present the status of current (2000) plans by the National Space Biomedical Research Institute to initiate research in this area of integrative physiology and medicine. Specifically, three example projects are discussed as potential stepping stones towards the ultimate goal of producing a digital human. These projects relate to developing a functional model of the human musculoskeletal system and the heart. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

NASA Discipline General Space Life Sciences↗

NASA NTRS2002

Alendronate as an Effective Countermeasure to Disuse Induced Bone loss

Microgravity, similar to diuse immobilization on earth, causes rapid bone loss. This loss is believed to be an adaptive response to the reduced musculoskelatal forces in space and occurs gradually enough that changes occurring during short duration space flight are not a concern. Bone loss, however, will be a major impediment for long duration missions if effective countermeasures are not developed and implemented. Bed rest is used to simulate the reduced mechanical forces in humans and was used to test the hypothesis that oral alendronate would reduce the effects of long duration (17 weeks) inactivity on bone. Eight male subjects were given daily oral doses of alendronate during 17 weeks of horizontal bed rest and compared with 13 male control subjects not given the drug. Efficacy was evaluated based on measurements of bone markers, calcium balance and bone density performed before, during and after the bed rest. The results show that oral alendronate attenuates most of the characteristic changes associated with long duration bed rest and presumably space flight.

LeBlanc, Adrian D.↗

NASA NTRS2004

Cellular Mechanisms Underlying Bone-Forming Cell Proliferative Response to Hypergravity

Life on Earth has evolved under the continuous influence of gravity (1-g). As humans explore and develop space, however, we must learn to adapt to an environment with little or no gravity. Studies indicate that lack of weightbearing for vertebrates occurring with immobilization, paralysis, or in a microgravity environment may cause muscle and bone atrophy through cellular and subcellular level mechanisms. We hypothesize that gravity is needed for the efficient transduction of cell growth and survival signals from the extra-cellular matrix (ECM) (consisting of molecules such as collagen, fibronectin, and laminin) in mechanosensitive tissues. We test for the presence of gravity-sensitive pathways in bone-forming cells (osteoblasts) using hypergravity applied by a cell culture centrifuge. Stimulation of 50 times gravity (50-g) increased proliferation in primary rat osteoblasts for cells grown on collagen Type I and fibronectin, but not on laminin or uncoated surfaces. Survival was also enhanced during hypergravity stimulation by the presence of ECM. Bromodeoxyuridine incorporation in proliferating cells showed an increase in the number of actively dividing cells from about 60% at 1-g to over 90% at 25-g. Reverse transcription-polymerase chain reaction was used to test for all possible integrins. Our combined results indicate that beta1 and/or beta3 integrin subunits may be involved. These data indicate that gravity mechanostimulation of osteoblast proliferation involves specific matrix-integrin signalling pathways which are sensitive to g-level. Further research to define the mechanisms involved will provide direction so that we may better adapt and counteract bone atrophy caused by the lack of weightbearing.

Vercoutere, W.↗

NASA NTRS2008

Development of an Inline Urine Monitoring System for the International Space Station

Human exposure to microgravity during spaceflight causes bone loss. Calcium and other metabolic byproducts are excreted in urine voids. Frequent and accurate measurement of urine void volume and constituents is essential to determining crew bone loss and the effectiveness of countermeasures. Previous US Space Shuttle (SS) Urine Monitoring System (UMS) technology was unable to accurately measure urine void volumes due to cross contamination between users and fluid system instabilities. Currently, urine voids must be collected manually in a flexible plastic bag containing a known tracer quantity. The crew member must completely mix the bag then withdraw a representative syringe sample for later ground analysis. The current bag system accuracy is highly dependent on mixing technique. The International Space Station (ISS) UMS has been developed as an automated device that collects urine from the Waste and Hygiene Compartment (WHC) urinal funnel interface, separates the urine, measures the void volume, and allows for syringe sampling. After operations, the ISS UMS delivers the urine to the WHC for normal processing then flushes its plumbing with a small water volume. The current ISS UMS design incorporates an innovative rotary separator that minimizes foaming, greatly reduces cross contamination between urine voids (< 0.5 ml urine), and provides accurate volume measurements (< +/- 2% error for 100 to 1000 ml void volumes). The system performance has been validated with extensive ground tests and reduced gravity aircraft flights. The lockersized ISS UMS is currently being modified to interface with the ISS Node 3 WHC Russian ACY hardware. The operation principles, characteristics, and results are outlined in the paper.

Broyan, James Lee, Jr.↗

NASA NTRS2009

Using the Enhanced Daily Load Stimulus Model to Quantify the Mechanical Load and Bone Mineral Density Changes Experienced by Crew Members on the International Space Station

Despite the use of exercise countermeasures during long-duration space missions, bone mineral density (BMD) and predicted bone strength of astronauts continue to show decreases in the lower extremities and spine. This site-specific bone adaptation is most likely caused by the effects of microgravity on the mechanical loading environment of the crew member. There is, therefore, a need to quantify the mechanical loading experienced on Earth and on-orbit to define the effect of a given "dose" of loading on bone homeostasis. Gene et al. recently proposed an enhanced DLS (EDLS) model that, when used with entire days of in-shoe forces, takes into account recently developed theories on the importance of factors such as saturation, recovery, and standing and their effects on the osteogenic response of bone to daily physical activity. This algorithm can also quantify the tinting and type of activity (sit/unload, stand, walk, run or other loaded activity) performed throughout the day. The purpose of the current study was to use in-shoe force measurements from entire typical work days on Earth and on-orbit in order to quantify the type and amount of loading experienced by crew members. The specific aim was to use these measurements as inputs into the EDLS model to determine activity timing/type and the mechanical "dose" imparted on the musculoskeletal system of crew members and relate this dose to changes in bone homeostasis.

Genc, K. O.↗

NASA NTRS1991

Effects of microgravity on the immune system

Changes in resistance to bacterial and viral infections in Apollo crew members has stimulated interest in the study of immunity and space flight. Results of studies from several laboratories in both humans and rodents have indicated alterations after space flight that include the following immunological parameters: thymus size, lymphocyte blastogenesis, interferon and interleukin production, natural killer cell activity, cytotoxic T-cell activity, leukocyte subset population distribution, response of bone marrow cells to colony stimulating factors, and delayed hypersensitivity skin test reactivity. The interactions of the immune system with other physiological systems, including muscle, bone, and the nervous system, may play a major role in the development of these immunological parameters during and after flight. There may also be direct effects of space flight on immune responses.

Sonnenfeld, Gerald↗

NASA NTRS2002

Commercial Instrumentation Technology Associates Inc. Biomedical Experiments Payload (CIBX-2)

Experiments to find solutions for a range of biomedical issues are being hosted by the Commercial Instrumentation Technology Associates Inc. (ITA) Biomedical Experiments (CIBX-2) payload. This research encompasses more than 20 separate experiments including cancer research, commercial experiments and hands-on student experiments from 10 schools as part of ITA's ongoing University Among the Stars program. Protein crystal growth experiments will address the structure of urokinase - a protein that has been identified as a key enzyme in the spread of brain, lung, colon, prostate and breast cancers. Crystals of Bence Jones, a protein associated with bone cancer, will also be grown. Understanding their structures may help scientists develop treatments. In a related area, the Microencapsulation of Drugs (MEPS) is an anti-cancer drug delivery system, based on a 10-year partnership with NASA's Johnson Space Center. On this mission, the co-encapsulation of antibodies and immune stimulants will be made in submicron microcapsules to target pulmonary and bacterial infections.

Morrison, Dennis↗

NASA NTRS1999

An overview of vertebrate mineralization with emphasis on collagen-mineral interaction

The nucleation, growth, and development of mineral crystals through their interaction principally with collagen in normal bone and calcifying tendon have been elaborated by applying a number of different techniques for analysis of the inorganic and organic constituents of these tissues. The methods have included conventional and high voltage electron microscopy, electron diffraction, microscopic tomography and 3D image reconstruction, and atomic force microscopy. This summary presents results of these studies that have now characterized the size, shape, and aspects of the chemical nature of the crystals as well as their orientation, alignment, location, and distribution with respect to collagen. These data have provided the means for understanding more completely the formation and strength of the collagen-mineral composite present in most vertebrate calcifying tissues and, from that information, a basis for the adaptation of such tissues under mechanical constraints. In the context of the latter point, other data are given showing effects on collagen in bone cell cultures subjected to the unloading parameters of spaceflight. Implications of these results may be particularly relevant to explaining loss of bone by humans and other vertebrate animals during missions in space, during situations of extended fracture healing, long-term bedrest, physical immobilization, and related conditions. In a broader sense, the data speak to the response of bone and mineralized vertebrate tissues to changes in gravitational loading and applied mechanical forces in general.

Non-NASA Center↗

NASA NTRS1999

Mineralization and growth of cultured embryonic skeletal tissue in microgravity

Microgravity provides a unique environment in which to study normal and pathological phenomenon. Very few studies have been done to examine the effects of microgravity on developing skeletal tissue such as growth plate formation and maintenance, elongation of bone primordia, or the mineralization of growth plate cartilage. Embryonic mouse premetatarsal triads were cultured on three space shuttle flights to study cartilage growth, differentiation, and mineralization, in a microgravity environment. The premetatarsal triads that were cultured in microgravity all formed cartilage rods and grew in length. However, the premetatarsal cartilage rods cultured in microgravity grew less in length than the ground control cartilage rods. Terminal chondrocyte differentiation also occurred during culture in microgravity, as well as in the ground controls, and the matrix around the hypertrophied chondrocytes was capable of mineralizing in both groups. The same percentage of premetatarsals mineralized in the microgravity cultures as mineralized in the ground control cultures. In addition, the sizes of the mineralized areas between the two groups were very similar. However, the amount of 45Ca incorporated into the mineralized areas was significantly lower in the microgravity cultures, suggesting that the composition or density of the mineralized regions was compromised in microgravity. There was no significant difference in the amount of 45Ca liberated from prelabeled explants in microgravity or in the ground controls.

NASA Discipline Developmental Biology↗

NASA NTRS2006

International Space Station: Transitional Platform for Moon and Mars

Humans on the path to Mars are employing the Space Station to better understand the Life Sciences issues during long duration space flight. In this phase the problems, for example, of bone loss, skeletal muscle atrophy and radiation will be prioritized for countermeasure development. This presentation will feature NASA's critical path to the Moon and Mars as the initial blueprint for addressing these Human Life Sciences challenges necessary to accomplish a successful Mars transit, surface exploration and return to Earth. A Moon base will be the test bed for resolving the engineering obstacles for later establishment of the Mars Crew Habitat. Current engineering concept scenarios for Moon and Mars bases plus Mars transit vehicles will receive the final focus.

Greeniesen, Michael C.↗

NASA NTRS2011

An Integrated Musculoskeletal Countermeasure Battery for Long-Duration Lunar Missions

During extended periods of skeletal unloading, losses in strength and density of the proximal femur will occur. In long-duration spaceflight, resistive exercise is used to replace the normal loads exerted on the spine and hip. At the present time, there is no conclusive evidence that hip bone loss has been prevented in this scenario. Our group has recently developed and clinically evaluated a multifunctional exercise system, the Combined Countermeasure Device (CCD). The CCD comprises a low-footprint Stuart Platform for lower-body resistance exercise and balance training, and a cardiovascular exercise bicycle. A consideration for resistance exercise was targeting of the hip abductor and adductor muscles, which attach directly at the hip and which should subject it to the largest loads. In our training study, we found that CCD exercise increased hip adductor and abductor strength, and modeling results suggest that this exercise exerts forces on the hip of approx. 4-6 body weights at 1g, compared to forces of approx.2.5 body weight y squatting exercise. In our current study, we hypothesize that abductor and adductor exercise will increase the density and strength of the proximal femur.

Lang, T. F.↗

NASA NTRS2016

Biomechanical Modeling of the Deadlift Exercise on the HULK Device to Improve the Efficacy of Resistive Exercise Microgravity Countermeasures

Extended spaceflight typically results in the loss of muscular strength and bone density due to exposure to microgravity. Resistive exercise countermeasures have been developed to maintain musculoskeletal health during spaceflight. The Advanced Resistive Exercise Device (ARED) is the "gold standard" of available devices; however, its footprint and volume are too large for use in space capsules employed in exploration missions. The Hybrid Ultimate Lifting Kit (HULK) device, with its smaller footprint, is a prototype exercise device for exploration missions. This work models the deadlift exercise being performed on the HULK device using biomechanical simulation, with the long-term goal to improve and optimize astronauts' exercise prescriptions, to maximize the benefit of exercise while minimizing time and effort invested.

Countermeasures↗

NASA NTRS2017

Implicit Formulation of Muscle Dynamics in OpenSim

Astronauts lose bone and muscle mass during spaceflight. Exercise countermeasure is the primary method for counteracting bone and muscle mass loss in space. New spacecraft exercise device concepts are currently being developed for the NASAs new crew exploration vehicle. The NASA Digital Astronaut Project (DAP) uses computational modeling to help determine if the new exercise devices will be effective as countermeasures. The NASA Digital Astronaut Project is developing the ability to utilize predictive simulation to provide insight into the change in kinematics and kinetics with a change in device and gravitational environment (1-g versus 0-g). For example, in space exercise the subject's body weight is applied in addition to the loads prescribed for musculoskeletal maintenance. How and where these loads are applied obviously directly impacts bone and tissue loads. Additionally, due to space vehicle structural requirements, exercise devices are often placed on vibration isolation systems. This changes the apparent impedance or stiffness of the device as seen by the user. Data collection under these conditions is often impractical and limited. Predictive modeling provides a means to have a virtual subject to test hypotheses. Predictive simulation provides a virtual subject for which we are able to perform studies such as sensitivity to device loading and vibration isolation without the need for laboratory kinematic or kinetic test data.Direct Collocation optimization provides an efficient means to perform task based optimization and predictive modeling. It is relatively straight forward to structure a physical exercise task in a Direct Collocation mathematical formulation: perform a motion such that you start at an initial pose, achieve a given amount of deflection i.e a squat, return to the initial pose, and minimize muscle activation cost. Direct Collocation is advantageous in that it does not require numerical integration to evaluate the objective function. Instead, the system dynamics are transformed to discrete time and the optimizer is constrained such that the solution is not considered to be a valid unless the dynamic equations are satisfied at all time points. The simulation and optimization are effectively done simultaneously. Due to the implicit integration, time steps can be more coarse than in a differential equation solver. In a gait scenario this means that that the model constraints and cost function are evaluated at 100 nodes in the gait cycle versus 10,000 integration steps in a variable-step forward dynamic simulation. Furthermore, no time is wasted on accurate simulations of movements that are far from the optimum. Constrained optimization algorithms require a Jacobian matrix that contains the partial derivatives of each of the dynamic constraints with respect to of each of the state and control variables at all time points. This is a large but sparse matrix. An implicit dynamics formulation requires computation of the dynamic residuals f as a function of the states x and their derivatives, and controls u:f(x, dxdt, u) 0If the dynamics of musculoskeletal system are formulated implicitly, the Jacobian elements are often available analytically, eliminating the need for numerical differentiation; this is obviously computationally advantageous. Additionally, implicit formulation of musculoskeletal dynamics do not suffer from singularities from low mass bodies, zero muscle activation, or other stiff system or

physical exercise↗

NASA NTRS2009

Simulating Bone Loss in Microgravity Using Mathematical Formulations of Bone Remodeling

Most mathematical models of bone remodeling are used to simulate a specific bone disease, by disrupting the steady state or balance in the normal remodeling process, and to simulate a therapeutic strategy. In this work, the ability of a mathematical model of bone remodeling to simulate bone loss as a function of time under the conditions of microgravity is investigated. The model is formed by combining a previously developed set of biochemical, cellular dynamics, and mechanical stimulus equations in the literature with two newly proposed equations; one governing the rate of change of the area of cortical bone tissue in a cross section of a cylindrical section of bone and one governing the rate of change of calcium in the bone fluid. The mechanical stimulus comes from a simple model of stress due to a compressive force on a cylindrical section of bone which can be reduced to zero to mimic the effects of skeletal unloading in microgravity. The complete set of equations formed is a system of first order ordinary differential equations. The results of selected simulations are displayed and discussed. Limitations and deficiencies of the model are also discussed as well as suggestions for further research.

Pennline, James A.↗

NASA NTRSDate not supplied

In-Space Inspection Needs: Opportunities for advanced NDE tools such as x-ray CT for additively manufactured parts, in-situ resource utilization, geological applications, and more

It is now 50 years since the first human presence on the surface of the Moon and as we strive to return with women and men in the next few years, we embrace new technical challenges, goals, and innovative solutions to address 21st century objectives. These new ambitions carry fresh challenges and risks, with the field of NDE playing an increasingly more relevant role towards meeting these essential goals. In recent years, more advanced NDE tools have triggered a rapid expansion of applications for the space industry. In particular, x-ray Computed Tomography (CT) has proven to be a trusted and powerful asset for spaceflight hardware inspection, as well as applied geotechnical analysis for natural materials (e.g., rocks, soils) for NASA and across industry. However, such methods have yet to be extended to “deep space” applications such as those that are now part of the US National Space Policy Directive (SPD-1) and the accelerated push to return humans to the Moon (i.e., Artemis). For this reason, advancing these powerful Earth-based laboratory methods via new technologies, integrated computational solutions, and creative engineering approaches is directly aligned with national space policies, as well as with multiple NASA Strategic Plan priorities. The use of x-ray CT at scales as fine as a few microns or smaller can identify spacecraft part failure modes relevant to quality assurance for flight hardware and AM parts such as those recently developed for ISS. This technology could also identify valuable metallic phases within geological materials (i.e., rocks or drill cores), enabling resource-relevant triage of samples for In-Situ Resource Utilization (ISRU) and high science value sample return to Earth laboratories. There is also significant application for 3D imaging tools for medical use such as inspecting protective gear as well as bone density degradation studies which are critical in establishing a sustained presence in space. Timing for development of these tools for space use is advantageous as we prepare for new opportunities in the next few years and recognize recent commercial technology advancements which make it feasible. Moreover, as NASA strives to take full advantage of developments in AM technologies, including In-Space Manufacturing (ISM), it is widely recognized that NDE tools such as CT will play an essential role in acceptance of these parts for widespread use. New in-space 3D inspection tools with complimentary technology such as AI-based automated feature recognition (accelerated by machine learning), rapid compositional analysis, and advanced sample manipulation, would be a game-changing step toward a new class of crew-based laboratory sensors once human outposts on the Moon are established.

In-Space Non-Destructive Evaluation↗