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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS2006

Human Bone-Forming Chondrocytes Cultured in the Hydrodynamic Focusing Bioreactor Retain Matrix Proteins: Similarities to Spaceflight Results

Fracture healing, crucial to a successful Mars mission, involves formation of a cartilaginous fracture callus which differentiates, mineralizes, ossifies and remodels via the endochondral process. Studies of spaceflown and tailsuspended rats found that, without loading, fracture callus formation and cartilage differentiation within the callus were minimal. We found delayed differentiation of chondrocytes within the rat growth plate on Cosmos 1887, 2044, and Spacelab 3. In the current study, differentiation of human bone-forming chondrocytes cultured in the hydrodynamic focusing bioreactor (HFB) was assessed. Human costochondral chondrocytes in suspension were aggregated overnight, then cultured in the HFB for 25 days. Collagen Type II, aggrecan and unsulfated chondroitin were found extracellularly and chondroitin sulfates 4 and 6 within the cell. Lack of secretion was also found in pancreatic cells of spaceflown rats, and in our SL3 studies. The HFB can be used to study cartilage differentiation in simulated microgravity.

Duke, P. J.↗
NASA NTRS2013

Use of the International Space Station as an Exercise Physiology Lab

The International Space Station (ISS) is now in its prime utilization phase with great opportunity to use the ISS as a lab. With respect to exercise physiology there is considerable research opportunity. Crew members exercise for up to 2 hours per day using a cycle ergometer, treadmill, and advanced resistive exercise device (ARED). There are several ongoing exercise research studies by NASA, ESA and CSA. These include studies related to evaluation of new exercise prescriptions (SPRINT), evaluation of aerobic capacity (VO2max), biomechanics (Treadmill Kinematics), energy expenditure during spaceflight (Energy), evaluation of cartilage (Cartilage), and evaluation of cardiovascular health (Vascular). Examples of how ISS is used for exercise physiology research will be presented.

Ploutz-Snyder, Lori↗
NASA NTRS2016

Femoral Head Bone Loss Following Short and Long-Duration Spaceflight

Exposure to mechanical unloading during spaceflight is known to have significant effects on the musculoskeletal system. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. The 30-day BionM1 and the 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight and furthermore would result in significant tissue alterations. MicroCT analysis of BionM1 femurs revealed 31 decrease in bone volume ratio, a 14 decrease in trabecular thickness, and a 20 decrease in trabecular number in the femoral head of space-flown mice. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. However, mice from RR1 exhibited significant bone loss in the femoral head but did not exhibit the severe aging and disease-like phenotype observed during BionM1. This may be due to increased physical activity in the RH hardware. Immunohistochemical analysis of the epiphyseal plate and investigation of cellular proliferation and differentiation pathways within the marrow compartment and whole bone tissue is currently being conducted to determine alterations in stem cell-based tissue regeneration between these experiments. Our results show that the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight femurs from BionM1 indicate onset of an accelerated aging-like phenotype with signs of osteoarthritic disease shown by disruption of the epiphyseal boundary and endochondral ossification. These effects are likely caused by a failure of stem cells to regenerate degraded tissues and may have significant implications for bone and cartilage health following extensive periods of mechanical unloading during long-duration spaceflight.

stem cells↗
NASA NTRS2016

Femoral Head Bone Loss Following Short and Long-Duration Spaceflight

Exposure to mechanical unloading during spaceflight is known to have significant effects on the musculoskeletal system. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. The 30-day BionM1 and the 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight and furthermore would result in significant tissue alterations. MicroCT analysis of BionM1 femurs revealed 31% decrease in bone volume ratio, a 14% decrease in trabecular thickness, and a 20% decrease in trabecular number in the femoral head of space-flown mice. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. However, mice from RR1 exhibited significant bone loss in the femoral head but did not exhibit the severe aging and disease-like phenotype observed during BionM1.This may be due to increased physical activity in the RH hardware. Immunohistochemical analysis of the epiphyseal plate and investigation of cellular proliferation and differentiation pathways within the marrow compartment and whole bone tissue is currently being conducted to determine alterations in stem cell-based tissue regeneration between these experiments. Our results show that the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight femurs from BionM1 indicate onset of an accelerated aging-like phenotype with signs of osteoarthritic disease shown by disruption of the epiphyseal boundary and endochondral ossification. These effects are likely caused by a failure of stem cells to regenerate degraded tissues and may have significant implications for bone and cartilage health following extensive periods of mechanical unloading during long-duration spaceflight.

microgravity↗
DOE OSTI2022

Interactions Between Diabetes Mellitus and Osteoarthritis: From Animal Studies to Clinical Data

Diabetes mellitus (DM) and osteoarthritis (OA) are commonly known metabolic diseases that affect a large segment of the world population. These two conditions share several risk factors such as obesity and aging; however, there is still no consensus regarding the direct role of DM on OA development and progression. Interestingly, both animal and human studies have yielded conflicting results, with some showing a significant role for DM in promoting OA, while others found no significant interactions between these conditions. In this review, we will discuss preclinical and clinical data that assessed the interaction between DM and OA. We will also discuss possible mechanisms associated with the effect of high glucose on the articular cartilage and chondrocytes. An emerging theme dominates the breath of published work in this area: most of the studies discussed in this review do not take into consideration the role of other factors such as the type of diabetes, age, biological sex, type of animal model, body mass index, and the use of pain medications when analyzing and interpreting data. Therefore, future studies should be more rigorous when designing experiments looking at DM and its effects on OA and should carefully account for these confounding factors, so that better approaches can be developed for monitoring and treating patients at risk of OA and DM.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1999

Microgravity cultivation of cells and tissues

In vitro studies of cells and tissues in microgravity, either simulated by cultivation conditions on earth or actual, during spaceflight, are expected to help identify mechanisms underlying gravity sensing and transduction in biological organisms. In this paper, we review rotating bioreactor studies of engineered skeletal and cardiovascular tissues carried out in unit gravity, a four month long cartilage tissue engineering study carried out aboard the Mir Space Station, and the ongoing laboratory development and testing of a system for cell and tissue cultivation aboard the International Space Station.

Review, Tutorial↗
DOE OSTI2023

All-polymer nanocomposites having superior strength, toughness and ultralow energy dissipation

Toughening polymers has attracted significant interest. Traditionally, polymer toughness is enhanced by constructing polymer networks or introducing sacrificial bonds into the chains between crosslink points. These strategies, though, introduce pronounced energy dissipation and associated heat, both of which are undesirable under long-term cyclic loading, for example at the interface of implants in the human body. By incorporating single-chain nanoparticles (SCNPs) into linear polymer chains to generate all-polymer nanocomposites (APNCs), we have been able to achieve high strength, high toughness with low energy dissipation. Using a combination of simulation and experimental results, we are advancing a “SCNPs effect” where tightly cross-linked SCNPs produce a modulus contrast to achieve strengthening and toughening. Benefitting from the soft interface, the penetrable and deformable SCNPs cause the surrounding polymer chains to move in concert, significantly reducing the interfacial friction to achieve low energy dissipation. The intramolecular cross-linking of the SCNPs and adhesion between the SCNPs and polymer matrix are critical for realizing such high-performance systems. Based on a Gaussian regression model and back propagation (BP) neural network, the mechanical strength can be predicted and is supported by simulations. Finally, the APNC concept described can be applied to elastomers and gels, broadening its utilization in high-cycle and low-dissipation applications, like soft robots, flexible sensors and cartilage replacements, and artificial heart valves.

36 MATERIALS SCIENCE↗
DOE OSTI2024

ENERGY DISPERSIVE DIFFRACTION TOMOGRAPHY OF SHARK VERTEBRAL CENTRA

Shark vertebrae and their centra (vertebral bodies) are high-performance structures able to survive millions of cycles of high amplitude strain despite lacking a repair mechanism for accumulating damage. Shark centra consist of mineralized cartilage, a biocomposite of bioapatite (bAp), and collagen, and the nanocrystalline bAp's contribution to functionality remains largely uninvestigated. Using the multiple detector energy-dispersive diffraction (EDD) system at 6-BM-B, the Advanced Photon Source, and 3D tomographic sampling, the 3D functionality of entire centra were probed. Immersion in ethanol vs phosphate-buffered saline produces only small changes in bAp d-spacing within a great hammerhead centrum. EDD mapping under in situ loading was performed an entire blue shark centrum, and 3D maps of bAp strain showed the two structural zones of the centrum, the corpus calcareum and intermedialia, contained opposite-signed strains approaching 0.5%, and application of similar to 8% nominal strain did not alter these strain magnitudes and their spatial distribution.

Park, Jun-Sang↗
DOE OSTI2025

Motion of Molecules in Supramolecular Scaffolds Enhances Bone Regeneration

The regeneration of human tissues is a great scientific challenge and a critical factor to achieve a long healthspan and prevent disabilities due to injury or disease. Materials chemistry can contribute to this goal with the development of bioactive supramolecular systems that can signal cells for regeneration. Recent work in our laboratory using in vivo models of spinal cord injury and cartilage regeneration has demonstrated that the motion of bioactive molecules in supramolecular scaffolds enhances receptor signaling. We report here on a novel molecular strategy to control supramolecular motion in filamentous assemblies using bone regeneration as a functional target. The supramolecular assemblies are composed of monomers that arrange, by design, with either parallel or antiparallel β-sheets, and some of them contain a terminal peptide sequence that binds BMP-2. We found that parallel β-sheet supramolecular assemblies promote greater osteogenic differentiation of progenitor cells in vitro relative to antiparallel assemblies, as well as superior quality of newly regenerated bone in a rat model of spinal fusion. Furthermore, these assemblies drastically reduce the dangerous supraphysiological dose of BMP-2 used clinically for spinal fusion. Here, we attribute the enhanced bioactivity to the weaker nature of hydrogen bonds in parallel relative to antiparallel β-sheet assemblies, which in turn allows greater supramolecular motion and cell signaling of the growth factor-binding molecules.

Anatomy↗
DOE OSTI2025

Creb5 controls its own expression and directly induces the joint interzone regulatory program

Prior studies have indicated that the transcription factor Creb5 is expressed in the joint interzone, which contains the progenitors for all synovial joint tissues in both mouse and human embryos. In the absence of Creb5 function, most synovial joint interzones fail to form and the cartilage templates in the long bones remain fused. This earlier work did not clarify whether Creb5 initiates a cascade of signaling molecules, such as growth and differentiation factor 5 (Gdf5) and Wnt-family members, that in turn induce the formation of the joint interzone, or instead directly activates the expression of joint interzone markers. In the present study, an integrative analysis of the transcriptome, chromatin accessibility, and Creb5-occupancy in joint progenitors revealed that Creb5 directly binds to both its own two promoters and to the regulatory regions of Gdf5 and Sfrp2, each of whose expression in the joint interzone is Creb5-dependent. Functional enhancer analysis indicated that Creb5 binding sites in either the two Creb5 promoters, or in Gdf5 and Sfrp2 regulatory elements are necessary for these sequences to drive transgene expression in the developing synovial joints. While Creb5 directly drives Gdf5 and Sfrp2 expression in the inner joint interzone, Creb5 activates Barx1 expression specifically in the outer joint interzone. Our findings indicate that Creb5 initiates a regulatory network that both promotes the formation of synovial joints, and subsequently activates distinct transcriptional targets in the inner versus the outer regions of the joint interzone, thus regionalizing gene expression in the developing joint.

Zhang, Cheng-Hai↗
DOE OSTI2023

Identification of conserved skeletal enhancers associated with craniosynostosis risk genes

Abstract Craniosynostosis, defined by premature fusion of one or multiple cranial sutures, is a common congenital defect affecting more than 1/2000 infants and results in restricted brain expansion. Single gene mutations account for 15%–20% of cases, largely as part of a syndrome, but the majority are nonsyndromic with complex underlying genetics. We hypothesized that the two noncoding genomic regions identified by a GWAS for craniosynostosis contain distal regulatory elements for the risk genes BMPER and BMP2. To identify such regulatory elements, we surveyed conserved noncoding sequences from both risk loci for enhancer activity in transgenic Danio rerio. We identified enhancers from both regions that direct expression to skeletal tissues, consistent with the endogenous expression of bmper and bmp2. For each locus, we also found a skeletal enhancer that also contains a sequence variant associated with craniosynostosis risk. We examined the activity of each enhancer during craniofacial development and found that the BMPER-associated enhancer is active in the restricted region of cartilage closely associated with frontal bone initiation. The same enhancer is active in mouse skeletal tissues, demonstrating evolutionarily conserved activity. Using enhanced yeast one-hybrid assays, we identified transcription factors that bind each enhancer and observed differential binding between alleles, implicating multiple signaling pathways. Our findings help unveil the genetic mechanism of the two craniosynostosis risk loci. More broadly, our combined in vivo approach is applicable to many complex genetic diseases to build a link between association studies and specific genetic mechanisms.

He(何璇), Xuan Anita (ORCID:0000000313221972)↗
DOE OSTI2022

Bioapatite in shark centra studied by wide-angle and by small-angle X-ray scattering

Members of subclass Elasmobranchii possess cartilage skeletons; the centra of many species are mineralized with a bioapatite, but virtually nothing is known about the mineral's organization. This study employed high-energy, small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS, i.e. X-ray diffraction) to investigate the bioapatite crystallography within blocks cut from centra of four species (two carcharhiniform families, one lamniform family and 1-ID of the Advanced Photon Source). All species' crystallographic quantities closely matched and indicated a bioapatite closely related to that in bone. The centra's lattice parameters a and c were somewhat smaller and somewhat larger, respectively, than in bone. Nanocrystallite sizes (WAXS peak widths) in shark centra were larger than typical of bone, and little microstrain was observed. Compared with bone, shark centra exhibited SAXS D-period peaks with larger D magnitudes, and D-period arcs with narrower azimuthal widths. The shark mineral phase, therefore, is closely related to that in bone but does possess real differences which probably affect mechanical property and which are worth further study.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

CD206 + Trem2 + macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice

Post-traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and other connective tissues in the joint. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus, or by intra-articular fractures. In humans, ~50% of joint injuries progress to PTOA, while the rest spontaneously resolve. To better understand molecular programs contributing to PTOA development or resolution, we examined injury-induced fluctuations in immune cell populations and transcriptional shifts by single-cell RNA sequencing of synovial joints in PTOA-susceptible C57BL/6J (B6) and PTOA-resistant MRL/MpJ (MRL) mice. We identified significant differences in monocyte and macrophage subpopulations between MRL and B6 joints. A potent myeloid-driven anti-inflammatory response was observed in MRL injured joints that significantly contrasted the pro-inflammatory signaling seen in B6 joints. Multiple CD206 + macrophage populations classically described as M2 were found enriched in MRL injured joints. These CD206 + macrophages also robustly expressed Trem2 , a receptor involved in inflammation and myeloid cell activation. These data suggest that the PTOA resistant MRL mouse strain displays an enhanced capacity of clearing debris and apoptotic cells induced by inflammation after injury due to an increase in activated M2 macrophages within the synovial tissue and joint space.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

On the progress of 3D-printed hydrogels for tissue engineering

Additive manufacturing or more commonly known as 3D printing, is currently driving innovations and applications in diverse fields such as prototyping, manufacturing, aerospace, education, and medicine. Recent technological and materials research breakthroughs have enabled 3D bioprinting, where biomaterials and cells are used to create scaffolds and functional living tissues (e.g. skin, cartilage, etc.). This prospective focuses on the classification and applications of hydrogels, and design considerations in their production (i.e. physical and biological parameters). Herein, the materials for 3D printing of hydrogels, such as biopolymers, synthetic polymers, and nanocomposites, are mainly discussed. More importantly, future perspectives on 3D printing hydrogels including new materials, 4D printing, emerging printing technologies, etc. and their importance in biomedical and bioengineering applications are discussed.

36 MATERIALS SCIENCE↗
NASA NTRS1977

Femoral development in chronically centrifuged rats

Groups of 30-d-old male and female rats were centrifuged at 2.00 G (RE, Rotation Experimental), 1.05 G (RC, Rotation Control) or exposed to the noise and wind of the centrifuge at 1.00 G (EC, Earth Control) for periods of 1, 2, 4, 8, and 16 weeks. Measurements of their femurs indicated that exposure to centrifugation a) decreased femoral length in RE animals, b) increased femoral length in RC animals, c) reduced femoral diameter in RE and RC animals, d) increased L/D ratios in RC animals, e) decreased L/D ratios in RE animals, f) increased femur length/body weight in RE animals, g) decreased cortical thickness (CT) in RE animals, h) increased relative CT in RE animals, and decreased it in RC animals, i) accelerated ossification in RC femoral heads, j) thinned and distorted RE epiphyseal plates, and k) thickened condylar cartilage in RE females. The effects tended to be strongly sexually dimorphic, with females more severely affected by the stress than males.

Smith, S. D.↗
NASA NTRS1980

Mechanical hand for gripping objects

End effector serves as "hand" for remote manipulator spacecraft system to grasp objects of various sizes. Device has built in flexible wrist joint "cartilage" for increased gripping force without significant strain on mechanical connections.

Clark, K. H.↗
NASA NTRS1981

Experiment K305: Quantitative analysis of selected bone parameters. Supplement 3A: Trabecular spacing and orientation in the long bones

Values of mean trabecular spacing computed from optical diffraction patterns of 1:1 X-ray micrographs of tibial metaphysis and those obtained by standard image digitization techniques show excellent agreement. Upper limits on values of mean trabecular orientation deduced from diffraction patterns and the images are also in excellent agreement. Values of the ratio of mean trabecular spatial density in a region of 300 micrometers distal to the downwardly directed convexity in the cartilage growth plate to the value adjacent to the plate determined for flight animals sacrificed at recovery were significantly smaller than values for vivarium control animals. No significant differences were found in proximal regions. No significant differences in mean trabecular orientation were detected. Decreased values of trabecular spatial density and of both obsteoblastic activity and trabecular cross-sectional area noted in collateral researches suggest decreased modeling activity under weightlessness.

Judy, M. M.↗
NASA NTRS1983

Effects of spaceflight on trabecular bone in rats

Alterations in trabecular bone were observed in growing male Wistar rats after 18.5 days of orbital flight on the COSMOS 1129 biosatellite. Spaceflight induced a decreased mass of mineralized tissue and an increased fat content of the bone marrow in the proximal tibial and humeral metaphyses. The osteoblast population appeared to decline immediately adjacent to the growth cartilage-metaphyseal junction, but osteoclast numbers were unchanged. These results suggested that bone formation may have been inhibited during spaceflight, but resorption remained constant. With the exception of trabecular bone mass in the proximal tibia, the observed skeletal changes returned to normal during a 29-day postflight period.

Jee, W. S. S.↗