Development and characterization of a low intensity vibrational system for microgravity studies

A large number of people living with type two diabetes suffer from a slow rate of wound healing. Also, some injuries, such as burns, can cause chronic wounds. Low-intensity vibrations have been investigated to promote wound healing. In authors’ previous research, a piezoelectric disc was bonded near the wound site to deliver low intensity vibration. It has been demonstrated that low intensity vibration promotes tissue perfusion, granulation tissue formation, and wound healing in diabetic mice. In this paper, a self-sensing feedback control system is designed to ensure vibration consistency. Such consistency is critical to the proposed treatment. The piezoelectric disc acts as an actuator and a sensor synchronously, i.e., a single piezoelectric disk bonded on the skin can produce vibrations and measure strain or stress simultaneously. No separate sensors are needed to deploy in the feedback control systems. Such integrated design eliminates sensors, which saves space and reduces complexity, and it is important to wearable devices. A bridge circuit is adopted in this work to enable the collocated control. The bridge circuit, piezoelectric disk, and tissue are modeled separately. Finally, a single-input single-output system model is established for the whole system, and a corresponding controller is designed. Responses based on the SISO model are simulated and analyzed. The important system parameters are investigated and discussed.

Isolated nuclei stiffen in response to low intensity vibration

This study examined whether loss of mechanotransduction in pluripotent mesenchymal stem cells (MSCs) disrupted repair of bulky DNA adducts, such as those induced by ultraviolet light or cisplatin. MSCs are important for the maintenance and responsiveness of skeletal tissues to environmental mechanical challenges. Beyond regulating proliferative and differentiative capacity of MSCs, emerging evidence suggests that physical activity is associated with improved recovery from DNA damage caused by environmental genotoxic stressors associated with stress and aging. Highlighting the possible crosstalk between DNA repair and bone health, defects in nucleotide excision repair (NER), which removes bulky DNA adducts, are associated with myelosuppression and progeroid aging phenotypes that result in bone defects and lipidodystrophies in mice. Cancer, early aging syndromes, and certain musculoskeletal diseases are associated with disruption of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that transduces environmental mechanical signals from the extracellular matrix into the nucleus of a cell. Loss of LINC complex elements is associated with breast cancer progression and poorer prognosis. We hypothesize that LINC-mediated mechanical stimulation into the nucleus is critical for repair of bulky DNA adducts. Our pilot project showed that mechanical stimulation applied in the form of low intensity vibration (LIV) improved NER of cisplatin-induced DNA adducts in cultured MSCs. Our findings show a 20% increase in repair of cisplatin-induced DNA adducts in LIV treated samples compared to non-vibrated samples at 24 hours (P<0.005). We also quantified the effect of LINC complex disruption on cisplatin-induced DNA damage removal. Intact MSCs showed significant adduct removal after 24 hours, while LINC disruption significantly reduced DNA repair (P<0.001). Furthermore, initial experiments suggest that LINC disrupted cells do not arrest at DNA repair checkpoints, therefore, loss of LINC complex may reduce entry into senescence increasing DNA mutagenesis. In conclusion, these findings suggest a novel interaction between mechanical stimulation, the DNA damage response, and LINC complex in DNA repair in multipotent mesenchymal stem cells. Furthermore, we suggest that LINC-mediated mechanical changes associated with LIV treatment may lead to novel therapeutic approaches to combat deleterious musculoskeletal conditions associated with anti-cancer treatments. Citation Format: Anamaria Gabriella Zavala, Nina Nikitina, Crystal Cantu, Dalia DeLaCruz, Gunes Uzer. Mechanical regulation of cisplatin-DNA adduct repair in mesenchymal stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5614.

Sun-mediated mechanical LINC between nucleus and cytoskeleton regulates βcatenin nuclear access

Postural instability caused by extended bed rest is alleviated by brief daily exposure to low magnitude mechanical signals

Beginning with the launch of the European Columbus module planned for December 2007, we approach a transition in the assembly of the International Space Station (ISS) that is of great importance for the sciences. During the following 18 months, we will operate the first experiments in Columbus physical science resource facilities and also launch and commission the Japanese Kibo module. In addition, two Multi-purpose Logistics Module (MPLM) flights will deliver the U.S. Combustion Integrated Rack (CIR) and Fluids Integrated Rack (FIR) along with their first science experiments. These facilities provide significant new capabilities for basic and applied physical science research in microgravity. New life support technologies will come online throughout 2008, and we will reach the milestone of a 6-person crew planned for April 2009. A larger crew enables significant more scientific use of all the facilities for the life of ISS. Planning for the use of the International Space Station as a national laboratory is also maturing as we near the completion of assembly, enabling access to ISS as a research platform for other government agencies and the private sector. The latest updates on National Laboratory implementation will also be provided in this presentation. At the same time as these significant increases in scientific capability, there have been significant ongoing accomplishments in NASA's early ISS research both exploration related and fundamental research. These accomplishments will be reviewed in context as harbingers of the capabilities of the International Space Station when assembly is complete. The Vision for Space Exploration serves to focus NASA's applied investigations in the physical sciences. However, the broader capability of the space station as a National Laboratory and as a nexus for international collaboration will also influence the study of gravity-dependent processes by researchers around the world.

<div class="htmlview paragraph">Developed as part of the suite of Space Station Biological Research Project (SSBRP) hardware to support research aboard the International Space Station (ISS), the Incubator is a temperature-controlled chamber for conducting life science research with small animal, plant and microbial specimens. The Incubator is designed for use only on the ISS and is transported to/from the ISS, unpowered and without specimens, in the Multi-Purpose Logistics Module (MPLM). The Incubator interfaces with the three SSBRP Host Systems; the Habitat Holding Racks (HHR), the Life Sciences Glovebox (LSG) and the 2.5 m Centrifuge Rotor (CR), providing investigators with the ability to conduct research in microgravity and at variable gravity levels of up to 2-g.</div> <div class="htmlview paragraph">The temperature within the Specimen Chamber can be controlled between 4° and 45<sup>o</sup>C. Cabin air is recirculated within the Specimen Chamber and can be exchanged with the ISS cabin at a rate of ≈ 50 cc/min. The humidity of the Specimen Chamber is monitored. The Specimen Chamber has a usable volume of ≈ 19 liters and contains two (2) connectors at 28v dc (60W) for science equipment; 5 dedicated thermometers for science; ports to support analog and digital signals from experiment unique sensors or other equipment; an Ethernet port; and a video port. It is currently manifested for UF-3 and will be integrated within the first SSBRP Habitat Holding Rack for launch.</div>

<p indent="0mm">The stability performance of sub-rail geotechnical structures under high-frequency vibration is an important aspect of further enhancing the travel speed of high-speed trains. In our previous experimental study on the dynamic behaviors of granular materials, fluidization and shear resistance reduction were observed during high-frequency vibration (even with relatively low vibration intensity), which are different from the dynamic behaviors under low-frequency vibration. The mechanism of the phenomenon owing to high-frequency vibration is still unclear, making the design of sub-rail geotechnical structures for future higher-speed railway lines difficult. Hence, a biaxial test is conducted via DEM simulation to obtain the variation of force chain quantity, anisotropy, and the ratio of inherent particles during vibration. These mesoscopic quantifications characterize the evolution of the skeleton structure, which bears the majority of the load in granular materials. During vibration, the results show that the evolution of force chains is consistent with the development and fluctuation of deviatoric stress. The variation scale of the skeleton structure is found to be proportional to the reduction in shear resistance of granular materials when subjected to high-frequency vibration. A larger scale of force chain network variation results in a greater reduction of normalized shear resistance.

All life forms have evolved under the constant force of gravity on Earth and developed ways to counterbalance acceleration load. In space, shear forces, buoyance-driven convection, and hydrostatic pressure are nullified or strongly reduced. When subjected to microgravity in space, the equilibrium between cell architecture and the external force is disturbed, resulting in changes at the cellular and sub-cellular levels (e.g., cytoskeleton, signal transduction, membrane permeability, etc.). Cosmic radiation also poses great health risks to astronauts because it has high linear energy transfer values that evoke complex DNA and other cellular damage. Space environmental conditions have been shown to influence apoptosis in various cell types. Apoptosis has important functions in morphogenesis, organ development, and wound healing. This review provides an overview of microgravity research platforms and apoptosis. The sections summarize the current knowledge of the impact of microgravity and cosmic radiation on cells with respect to apoptosis. Apoptosis-related microgravity experiments conducted with different mammalian model systems are presented. Recent findings in cells of the immune system, cardiovascular system, brain, eyes, cartilage, bone, gastrointestinal tract, liver, and pancreas, as well as cancer cells investigated under real and simulated microgravity conditions, are discussed. This comprehensive review indicates the potential of the space environment in biomedical research.

The structure and function of soleus muscle fibers undergo substantial remodeling under real or simulated microgravity conditions. However, unloading-induced changes in the functional activity of skeletal muscle primary myoblasts remain poorly studied. The purpose of our study was to investigate how short-term and long-term mechanical unloading would affect cultured myoblasts derived from rat soleus muscle. Mechanical unloading was simulated by rat hindlimb suspension model (HS). Myoblasts were purified from rat soleus at basal conditions and after 1, 3, 7, and 14 days of HS. Myoblasts were expanded in vitro, and the myogenic nature was confirmed by their ability to differentiate as well as by immunostaining/mRNA expression of myogenic markers. The proliferation activity at different time points after HS was analyzed, and transcriptome analysis was performed. We have shown that soleus-derived myoblasts differently respond to an early and later stage of HS. At the early stage of HS, the proliferative activity of myoblasts was slightly decreased, and processes related to myogenesis activation were downregulated. At the later stage of HS, we observed a decrease in myoblast proliferative potential and spontaneous upregulation of the pro-myogenic program.

Spaceflight and simulated microgravity both affect learning and memory, which are mostly controlled by the hippocampus. However, data about molecular alterations in the hippocampus in real or simulated microgravity conditions are limited. Adult Wistar rats were recruited in the experiments. Here we analyzed whether short-term simulated microgravity caused by 3-day hindlimb unloading (HU) will affect the glutamatergic and GABAergic systems of the hippocampus and how dynamic foot stimulation (DFS) to the plantar surface applied during HU can contribute in the regulation of hippocampus functioning. The results demonstrated a decreased expression of vesicular glutamate transporters 1 and 2 (VGLUT1/2) in the hippocampus after 3days of HU, while glutamate decarboxylase 67 (GAD67) expression was not affected. HU also significantly induced Akt signaling and transcriptional factor CREB that are supposed to activate the neuroprotective mechanisms. On the other hand, DFS led to normalization of VGLUT1/2 expression and activity of Akt and CREB. Analysis of exocytosis proteins revealed the inhibition of SNAP-25, VAMP-2, and syntaxin 1 expression in DFS group proposing attenuation of excitatory neurotransmission. Thus, we revealed that short-term HU causes dysregulation of glutamatergic system of the hippocampus, but, at the same time, stimulates neuroprotective Akt-dependent mechanism. In addition, most importantly, we demonstrated positive effect of DFS on the hippocampus functioning that probably depends on the regulation of neurotransmitter exocytosis.

West Virginia University (WVU) has created the Small Microgravity Research Facility (SMiRF) drop tower through a WVU Research Corporation Program to Stimulate Competitive Research (PSCoR) grant on its campus to increase direct access to inexpensive and repeatable reduced gravity research. In short, a drop tower is a tall structure from which experimental payloads are dropped, in a controlled environment, and experience reduced gravity or microgravity (i.e. "weightlessness") during free fall. Currently, there are several methods for conducting scientific research in microgravity including drop towers, parabolic flights, sounding rockets, suborbital flights, NanoSats, CubeSats, full-sized satellites, manned orbital flight, and the International Space Station (ISS). However, none of the aforementioned techniques is more inexpensive or has the capability of frequent experimentation repeatability as drop tower research. These advantages are conducive to a wide variety of experiments that can be inexpensively validated, and potentially accredited, through repeated, reliable research that permits frequent experiment modification and re-testing.;Development of the WVU SMiRF, or any drop tower, must take a systems engineering approach that may include the detailed design of several main components, namely: the payload release system, the payload deceleration system, the payload lifting and transfer system, the drop tower structure, and the instrumentation and controls system, as well as a standardized drop tower payload frame for use by those researchers who cannot afford to spend money on a data acquisition system or frame. In addition to detailed technical development, a budgetary model by which development took place is also presented throughout, summarized, and detailed in an appendix. After design and construction of the WVU SMiRF was complete, initial calibration provided performance characteristics at various payload weights, and full-scale checkout via experimentation provided repeatability characteristics of the facility. Based on checkout instrumentation, Initial repeatability results indicated a drop time of 1.26 seconds at an average of 0.06g, with a standard deviation of 0.085g over the period of the drop, and a peak impact load of 28.72g, with a standard deviation of 10.73g, for a payload weight of 113.8 lbs.;In order to thoroughly check out the facility, a full-scale, fully operational experiment was developed to create an experience that provides a comprehensive perspective of the end-user experience to the developer, so as to incorporate the details that may have been overlooked to the designer and/or developer, in this case, Kyle Phillips. The experiment that was chosen was to determine the effects of die swell, or extrudate

Crystals of proteins or macromolecules are at the basis of X-ray crystallography to reveal structural information necessary for the understanding of their likely mode of action. However, the structural resolution is strongly dependent on the crystalline quality, which is known to be related to gravity dependent processes. The facilities and instruments used so far to grow crystals in space have mostly focused on the growing of crystals for detailed post-flight analysis on ground, and less on the understanding of phenomena associated to the crystallisation processes. The Protein Crystallisation Diagnostics Facility (PCDF), developed by Astrium under contract of the European Space Agency (ESA), allows to study with several diagnostics means in situ the crystallisation of macromolecules over long periods in microgravity. In addition, several ground models with PCDF similar capabilities were developed to allow scientists to prepare their experiments. The PCDF is installed in the European Drawer Rack (EDR), on board ESA’s Columbus Laboratory module launched in February 2008 to the International Space Station (ISS) for research in microgravity on protein nucleation and assembling sequences. The PCDF configuration for this first mission accommodates four reactors, using the batch crystallization technique. Individual process control for temperature and concentration will allow several crystallizations of solutions to be performed. Each reactor will be observed by several optical diagnostics, including video microscopy, dynamic light scattering, and Mach–Zehnder interferometry. This paper presents the overall PCDF design and details the different diagnostics allowing the scientific community to use the PCDF in orbit for microgravity research on molecule assemblies grown from solutions.

Renal adaptation in space has been studied during various space missions since the early 70s. Technical and financial disadvantages of performing experiments under real microgravity conditions have warranted the conductance of relative studies under simulated weightlessness on earth. Arriving in microgravity leads to a redistribution of body fluids to the upper part of the body and an exaggerated extravasation very early in-flight. Plasma volume as well as skin evaporation and oral hydration are reduced, while total body water seems to remain stable. Urinary sodium is diminished and a substantial amount of sodium is retained outside the intravascular space. Glomerular filtration rate shows a transient mild increase. Urinary albumin excretion is reduced although initial studies had demonstrated the opposite. Examination of renal histopathology after exposure to simulated microgravity in rats revealed glomerular atrophy, interstitial edema, and degeneration of renal tubular cells. Acute urinary retention which has been reported during spaceflights can lead to certain medical complications that could compromise an entire mission. Kidney stone formation is another important potential hazard for any manned spaceflight. Increased kidney stone formation in space is attributed to several factors including reduced fluid intake, hypercalciuria, and the presence of nanobacteria. Nutritional and pharmacological interventions are currently recommended as preventive measures against renal stone formation in space travelers.

Recent advancements in stem cell biology, coupled with developments in space exploration, have opened new avenues for regenerative medicine. Microgravity environments in space induce significant physiological changes in the human body, such as muscle atrophy, decreased bone density, and immune system impairments, mimicking accelerated aging and chronic disease progression. These conditions offer a unique opportunity to study stem cell behavior, proliferation, and differentiation, which occur at a faster pace in space compared to Earth. The three-dimensional (3D) microgravity environment provides a more accurate representation of the human body’s natural state than traditional two-dimensional culture systems, fostering enhanced stem cell development. Among the various stem cells studied in space, mesenchymal stem cells (MSCs) have shown promise for therapeutic applications, including the treatment of stroke, cancer, and neurodegenerative diseases. Research aboard the International Space Station (ISS) has demonstrated that MSCs maintain their properties, proliferate, and differentiate under microgravity conditions, offering potential for future therapies. Additionally, MSCs exhibit resistance to space radiation, protecting astronauts from its harmful effects by promoting tissue repair and releasing regenerative factors. This radiation resistance, coupled with cryopreservation techniques, enables MSCs to be used in long-duration space missions. The ongoing research on MSCs in space not only supports astronaut health but also holds the potential to revolutionize regenerative medicine on Earth. By understanding how microgravity influences stem cell behavior, scientists are uncovering critical insights into tissue repair and cell function, paving the way for innovative treatments for aging-related diseases and other medical conditions. These findings highlight the broader implications of space-based stem cell research for advancing human health both in space and on Earth.