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All sourcesNASA NTRSDOE OSTI
NASA NTRS2018

Musculoskeletal Injuries in US Astronauts: Injury Prevention Strategies, Including Pre-Flight EVA Fitness Training, Return to Flight Following Injuries, and Post-Flight Reconditioning

Outline: Background; Terrestrial experience -Initial investigation into MSK (MusculoSKeletal) injuries -MSK Medicine Program -Training injuries -NBL (Neutral Buoyancy Laboratory) EMU (Extravehicular activity Mobility Unit) Work Hardening Program -Return to duty -Post-flight reconditioning program; Inflight musculoskeletal conditions; Lunar Surface Operations; Post-flight injuries.

Scheuring, Richard A.↗
NASA NTRS2011

Development of Head Injury Assessment Reference Values Based on NASA Injury Modeling

NASA is developing a new capsule-based, crewed vehicle that will land in the ocean, and the space agency desires to reduce the risk of injury from impact during these landings. Because landing impact occurs for each flight and the crew might need to perform egress tasks, current injury assessment reference values (IARV) were deemed insufficient. Because NASCAR occupant restraint systems are more effective than the systems used to determine the current IARVs and are similar to NASA s proposed restraint system, an analysis of NASCAR impacts was performed to develop new IARVs that may be more relevant to NASA s context of vehicle landing operations. Head IARVs associated with race car impacts were investigated by completing a detailed analysis of all of the 2002-2008 NASCAR impact data. Specific inclusion and exclusion criteria were used to select 4071 impacts from the 4015 recorder files provided (each file could contain multiple impact events). Of the 4071 accepted impacts, 274 were selected for numerical simulation using a custom NASCAR restraint system and Humanetics Hybrid-III 50th percentile numerical dummy model in LS-DYNA. Injury had occurred in 32 of the 274 selected impacts, and 27 of those injuries involved the head. A majority of the head injuries were mild concussions with or without brief loss of consciousness. The 242 non-injury impacts were randomly selected and representative of the range of crash dynamics present in the total set of 4071 impacts. Head dynamics data (head translational acceleration, translational change in velocity, rotational acceleration, rotational velocity, HIC-15, HIC-36, and the Head 3ms clip) were filtered according to SAE J211 specifications and then transformed to a log scale. The probability of head injury was estimated using a separate logistic regression analysis for each log-transformed predictor candidate. Using the log transformation constrains the estimated probability of injury to become negligible as IARVs approach zero. For the parameters head translational acceleration, head translational velocity change, head rotational acceleration, HIC-15, and HIC-36, conservative values (in the lower 95% confidence interval) that gave rise to a 5% risk of any injury occurring were estimated as 40.0 G, 7.9 m/s, 2200 rad/s2, 98.4, and 77.4 respectively. Because NASA is interested in the consequence of any particular injury on the ability of the crew to perform egress tasks, the head injuries that occurred in the NASCAR dataset were classified according to a NASA-developed scale (Classes I - III) for operationally relevant injuries, which classifies injuries on the basis of their operational significance. Additional analysis of the data was performed to determine the probability of each injury class occurring, and this was estimated using an ordered probit model. For head translational acceleration, head translational velocity change, head rotational acceleration, head rotational velocity, HIC-36, and head 3ms clip, conservative values of IARVs that produced a 5% risk of Class II injury were estimated as 50.7 G, 9.5 m/s, 2863 rad/s2, 11.0 rad/s, 30.3, and 46.4 G respectively. The results indicate that head IARVs developed from the NASCAR dataset may be useful to protect crews during landing impact.

Somers, Jeffrey T.↗
NASA NTRS2014

Injury Surveillance Among NASA Astronauts Using the Barell Injury Diagnosis Matrix

Astronauts perform physically demanding tasks and risk incurring musculoskeletal injuries during both groundbased training and missions. Increased injury rates throughout the history of the U.S. space program have been attributed to numerous factors, including an aging astronaut corps, increased Weightless Environment Training Facility (WETF) and Neutral Buoyancy Laboratory (NBL) training to construct the International Space Station, and improved clinical operations that promote injury prevention and reporting. With NASA program changes through the years (including retirement of the Shuttle program) and an improved training environment (including a new astronaut gym), there is no surveillance program to systematically track injury rates. A limited number of research projects have been conducted over the past 20 years to evaluate musculoskeletal injuries: (1) to evaluate orthopedic injuries from 1987 to 1995, (2) to describe upper extremity injuries, (3) to evaluate EVA spacesuit training related injuries, and (4) to evaluate in-flight musculoskeletal injuries. Nevertheless, there has been no consistently performed comprehensive assessment of musculoskeletal injuries among astronauts. The Barell Injury Diagnosis Matrix was introduced at the 2001 meeting of the International Collaborative Effort (ICE) on Injury Statistics. The Matrix proposes a standardized method of classifying body region by nature of injury. Diagnoses are coded using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding system. The purpose of this study is to assess the usefulness and complexity of the Barell Injury Diagnosis Matrix to classify and track musculoskeletal injuries among NASA astronauts.

Murray, J. D.↗
NASA NTRSDate not supplied

Development of the Suited Injury Modes and Effects Analysis for Identification of Top Injury Risks in Lunar Missions and Training

A new Exploration Extravehicular Activity Services (xEVAS) suit is being designed to replace the current Extravehicular Mobility Unit (EMU) for the National Aeronautics and Space Administration’s (NASA’s) Artemis program to return astronauts to the lunar surface. This new suit will allow for increased range of motion compared to the current EMU and Apollo era suits and additional features will enhance the health and safety of exploration. With the design of lunar missions and the xEVAS suit progressing, it is important to consider possible injuries and injury mechanisms that could occur in the suit. To address these concerns, the suited Injury Modes and Effects Analysis (IMEA) was developed to outline suited injury scenarios and rank them based on risk score. The IMEA documents possible scenarios and underlying mechanisms of injury. History has shown that more suit injuries occur during training than in flight; therefore, currently planned training events to prepare for lunar missions and tasks during lunar surface EVAs were considered. Each scenario is ranked with likelihood and consequence scorings based on our current understanding of suit and application of Artemis design reference missions. The scoring allowed identification of the high-risk cases that will drive further work in suited injury. Mechanisms of injury, injury outcomes, and mitigation strategies are evaluated within each scenario. The Suited Injury Summit was held on January 5, 2022, to vet the IMEA with external experts. This was an all-day virtual meeting with the suited injury team; ergonomists; suit engineers; safety engineers; the flight operations directorate; flight doctors; astronauts; astronaut strength, conditioning, and rehabilitation specialists (ASCRS); and external subject matter experts (SMEs). External SMEs consisted of surgeons with varying specialties. The intent of this meeting was to walk through the top injury risks identified in the analysis, identify any gaps that were not captured, and discuss mitigations. With participation from all groups, countless lessons-learned came from the Summit meeting. Using these, the top 10 risks have been identified: neutral buoyancy laboratory training, hand/glove injuries, poor suit fit, field training, specific EVA tasks/design of task, boots/ankle injuries, falls from heights, background radiation, repetitive contact, and ambulation/longdistance ambulation. Mitigation steps have also been determined for each of the top risks. The IMEA and documentation of top risks is a living document. Yearly meetings are planned to update the analysis and reevaluate top risks and mitigations. The IMEA is being used to drive work in suited injury, and this work will continue to evolve with IMEA and lunar mission updates.

Teresa Reiber↗
NASA NTRSDate not supplied

Development of the Suited Injury Modes and Effects Analysis for Identification of Top Injury Risks in Lunar Missions and Training

A new Exploration Extravehicular Activity Suit (xEVAS) is being designed to replace the current Extravehicular Mobility Unit (EMU) for the National Aeronautics and Space Administration’s (NASA’s) Artemis program to return astronauts to the lunar surface. This new suit will allow for increased range of motion compared the current EMU and Apollo era suits and will have additional features that will enhance the health and safety of exploration. With the design of lunar missions and the xEVAS progressing, it is important to consider possible injuries and injury mechanisms that could occur in the suit. To address these concerns, the suited Injury Modes and Effects Analysis (IMEA) was developed to outline suited injury scenarios and rank them based on risk score. The IMEA documents possible scenarios and underlying mechanisms of injury while wearing an extravehicular activity (EVA) suit. Tasks during lunar surface EVA as well as training events to prepare for lunar missions were considered as history has shown that more suit injuries occur during training than in flight. Each scenario is ranked with a consequence and likelihood scoring based on our current understanding of the suit and Artemis design reference missions to identify high-risk cases that will drive further work in suited injury. Injuries, mechanisms of injury, and mitigation strategies are evaluated within each scenario. The Suited Injury Summit was held on January 5, 2022, to vet the IMEA with external experts. This was an all-day virtual meeting with the suited injury team, ergonomists, suit engineers, safety engineers, the flight operations directorate, flight doctors, astronauts, astronaut strength, conditioning, and rehabilitation specialists (ASCRS), and external subject matter experts (SMEs). External SMEs consisted of surgeons with varying specialties. The intent of this meeting was to walk through the top injury risks identified in the analysis, identify any gaps that were not captured, and discuss mitigations. With participation from all groups, countless lessons-learned came from the Summit meeting. Using the lessons-learned and discussion from the Summit, the top 10 risks have been identified: neutral buoyancy laboratory training, hand/glove injuries, poor suit fit, field training, specific EVA tasks/design of task, boots/ankle injuries, falls from heights, background radiation, repetitive contact, and ambulation/long-distance ambulation. Mitigation steps have also been determined for each of the top risks. The IMEA and documentation of top risks is a living document. Yearly meetings are planned to update the analysis and reevaluate top risks and mitigations. The IMEA is being used to drive work in suited injury, and this work will continue to evolve with IMEA and lunar mission updates.

Teresa Reiber↗
NASA NTRSDate not supplied

Development of the Suited Injury Modes and Effects Analysis for Identification of Top Injury Risks in Lunar Missions and Training

A new Exploration Extravehicular Activity Suit (xEVAS) is being designed to replace the current Extravehicular Mobility Unit (EMU) for the National Aeronautics and Space Administration’s (NASA’s) Artemis program to return astronauts to the lunar surface. This new suit will allow for increased range of motion compared the current EMU and Apollo era suits and will have additional features that will enhance the health and safety of exploration. With the design of lunar missions and the xEVAS progressing, it is important to consider possible injuries and injury mechanisms that could occur in the suit. To address these concerns, the suited Injury Modes and Effects Analysis (IMEA) was developed to outline suited injury scenarios and rank them based on risk score. The IMEA documents possible scenarios and underlying mechanisms of injury while wearing an extravehicular activity (EVA) suit. Tasks during lunar surface EVA as well as training events to prepare for lunar missions were considered as history has shown that more suit injuries occur during training than in flight. Each scenario is ranked with a consequence and likelihood scoring based on our current understanding of the suit and Artemis design reference missions to identify high-risk cases that will drive further work in suited injury. Injuries, mechanisms of injury, and mitigation strategies are evaluated within each scenario. The Suited Injury Summit was held on January 5, 2022, to vet the IMEA with external experts. This was an all-day virtual meeting with the suited injury team, ergonomists, suit engineers, safety engineers, the flight operations directorate, flight doctors, astronauts, astronaut strength, conditioning, and rehabilitation specialists (ASCRS), and external subject matter experts (SMEs). External SMEs consisted of surgeons with varying specialties. The intent of this meeting was to walk through the top injury risks identified in the analysis, identify any gaps that were not captured, and discuss mitigations. With participation from all groups, countless lessons-learned came from the Summit meeting. Using the lessons-learned and discussion from the Summit, the top 10 risks have been identified: neutral buoyancy laboratory training, hand/glove injuries, poor suit fit, field training, specific EVA tasks/design of task, boots/ankle injuries, falls from heights, background radiation, repetitive contact, and ambulation/long-distance ambulation. Mitigation steps have also been determined for each of the top risks. The IMEA and documentation of top risks is a living document. Yearly meetings are planned to update the analysis and reevaluate top risks and mitigations. The IMEA is being used to drive work in suited injury, and this work will continue to evolve with IMEA and lunar mission updates.

Tessa Reiber↗
DOE OSTI2018

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model

The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood–brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood–brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

Blunt Impact Brain Injury using Cellular Injury Criterion

The Advanced Combat Helmet (\ACH") military specification (\mil-spec") requires a helmeted magnesium (\Mg") Department of Transportation (\DOT") headform be dropped vertically, with an impact speed of 3.1 m/s (10 ft/s), onto a steel hemispherical target. The pass/fail criteria are based on translational acceleration (150 G) alone, absent of any rotational component. Without a rotational component, the specification's injury risk application is limited to skull fracture and peripheral hematomas (subdural, subarachnoid), since this translational acceleration injury risk assessment is based on the Wayne State Tolerance Curve (\WSTC"). To provide a more comprehensive view of injury for the entire brain, an alternative approach is needed. To meet this need, we worked with a larger group called PANTHER, a collaboration between national laboratories, industry, and academia. Collaborations specific to research and results presented here come from efforts led by Mr. Ron Szalkowski and Mr. Sushant Malave, Ms. Alice Fawzi, and Dr. Christian Franck. We have developed a prototypical injury risk criterion based on the neuronal response to abrupt changes in general motion (translation, rotation, or both). The cellular-based mild traumatic brain injury (\cbmTBI") criterion utilizes both the strain and strain rate of brain tissue to account for the stretch and rate of stretch that occurs throughout the brain as a result of blunt impact to the head. We conducted physical experiments of an ACH-fitted magnesium headform, which produced repeatable headform peak accelerations. Then, we developed a simulation of the experiment, and validated the simulation output with the experimental data. We then substituted the magnesium headform with a human headform, consisting of skin, muscle, bone, gray matter, white matter, cerebral-spinal fluid, membranes, vasculature, intravertebral discs, airway and sinus. We quantified brain injury risk using the cbmTBI criterion, using the current mil-spec test and a modified test. The modified mil-spec test used an inclined anvil target that was located posterior to the crown of the helmet in the axial plane. While the current mil-spec test produced brain deformation from head translation alone, the modified test produced brain deformation from head translation and rotation, which is closer to most real world and combat theater impacts (e.g., such as occur in tertiary blast exposure). Compared to the current mil-spec test, the modified test produced elevated strains in the human digital twin. These data, mapped to the cbmTBI criterion, suggest increased injury risk for blunt impacts that cause rotation and translation, rather than just translation alone. Moreover, these data may lead to a rotational performance metric, which is rooted in the biology and pathology of the brain's response to impact and blast, and which should be used to improve next-generation helmet designs.

42 ENGINEERING↗
DOE OSTI2010

Injury and Mortality of Juvenile Salmon Entrained in a Submerged Jet Entering Still Water

Abstract Development of more eco-friendly hydroelectric facilities requires better understanding of the biological response of juvenile fish when they migrate through the turbines and other downstream passage facilities. Juvenile fall Chinook salmon Oncorhynchus tshawytscha were exposed to turbulent shear flows in a laboratory by using a fast-fish-to-slow-water mechanism in which test fish were carried by the fast-moving water of a submerged turbulent jet into the slow-moving water of a flume. Fish were released at six nozzle velocities: 6.1 (reference control), 12.2, 15.2, 18.3, 21.3, and 22.9 m/s. The onset of minor and major injuries occurred at 15.2 and 21.3 m/s, respectively. The acceleration magnitude threshold (m/s2) of major injury for the fast-fish-to-slow-water mechanism in this study was found to be significantly higher than that for a slow-fish-to-fast-water mechanism used in a previous study in which test fish were introduced into a turbulent jet from slow-moving water through an introduction tube placed just outside the edge of the jet. Fish responded differently and sustained different injuries when they were subjected to turbulent shear flows under the two exposure mechanisms. This information is applicable to the design and operation of turbines and spillways because these two tested mechanisms simulate the severe hydraulic events fish usually experience during passage at hydropower dams.

Deng, Zhiqun↗
DOE OSTI2014

Ultrasonic Nakagami-parameter characterization of parotid-gland injury following head-and-neck radiotherapy: A feasibility study of late toxicity

Purpose: The study aims to investigate whether Nakagami parameters—estimated from the statistical distribution of the backscattered ultrasound radio-frequency (RF) signals—could provide a means for quantitative characterization of parotid-gland injury resulting from head-and-neck radiotherapy. Methods: A preliminary clinical study was conducted with 12 postradiotherapy patients and 12 healthy volunteers. Each participant underwent one ultrasound study in which ultrasound scans were performed in the longitudinal, i.e., vertical orientation on the bilateral parotids. For the 12 patients, the mean radiation dose to the parotid glands was 37.7 ± 9.5 Gy, and the mean follow-up time was 16.3 ± 4.8 months. All enrolled patients experienced grade 1 or 2 late salivary-gland toxicity (RTOG/EORTC morbidity scale). The normal parotid glands served as the control group. The Nakagami-scaling and Nakagami-shape parameters were computed from the RF data to quantify radiation-induced parotid-gland changes. Results: Significant differences in Nakagami parameters were observed between the normal and postradiotherapy parotid glands. Compared with the control group, the Nakagami-scaling parameter of the postradiotherapy group decreased by 25.8% (p < 0.001), and the Nakagami-shape parameter decreased by 31.3% (p < 0.001). The area under the receiver operating characteristic curve was 0.85 for the Nakagami-scaling parameter and was 0.95 for the Nakagami-shape parameter, which further demonstrated the diagnostic efficiency of the Nakagami parameters. Conclusions: Nakagami parameters could be used to quantitatively measure parotid-gland injury following head-and-neck radiotherapy. Moreover, the clinical feasibility was demonstrated and this study provides meaningful preliminary data for future clinical investigation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Correlation of Injury Simulation with Clinical Assessment of Traumatic Brain Injury

This report contains a summary of our efforts to correlate head injury simulations predicting intracranial fluid cavitation with clinical assessments of brain injury from blunt impact to the head. Magnetic resonance imaging (MRI) data, collected on traumatic brain injury (TBI) subjects by researchers at the MIND Institute of New Mexico, was acquired for the current work. Specific blunt impact TBI case histories were selected from the TBI data for further study and possible correlation with simulation. Both group and single-subject case histories were examined. We found one single-subject case that was particularly suited for correlation with simulation. Diffusion tensor image (DTI) analysis of the TBI subject identified white matter regions within the brain displaying reductions in fractional anisotropy (FA), an indicator of local damage to the white matter axonal structures. Analysis of functional magnetic resonance image (fMRI) data collected on this individual identified localized regions of the brain displaying hypoactivity, another indicator of brain injury. We conducted high fidelity simulations of head impact experienced by the TBI subject using the Sandia head-neck-torso model and the shock physics computer code CTH. Intracranial fluid cavitation predictions were compared with maps of DTI fractional anisotropy and fMRI hypoactivity to assess whether a possible correlation exists. The ultimate goal of this work is to assess whether one can correlate simulation predictions of intracranial fluid cavitation with the brain injured sites identified by the fMRI and DTI analyses. The outcome of this effort is described in this report.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Correlation of Injury Simulation with Clinical Assessment of Traumatic Brain Injury

This report contains a summary of our efforts to correlate head injury simulations predicting intracranial fluid cavitation with clinical assessments of brain injury from blunt impact to the head. Magnetic resonance imaging (MRI) data, collected on traumatic brain injury (TBI) subjects by researchers at the MIND Institute of New Mexico, was acquired for the current work. Specific blunt impact TBI case histories were selected from the TBI data for further study and possible correlation with simulation. Both group and single-subject case histories were examined. We found one single-subject case that was particularly suited for correlation with simulation. Diffusion tensor image (DTI) analysis of the TBI subject identified white matter regions within the brain displaying reductions in fractional anisotropy (FA), an indicator of local damage to the white matter axonal structures. Analysis of functional magnetic resonance image (fMRI) data collected on this individual identified localized regions of the brain displaying hypoactivity, another indicator of brain injury. We conducted high fidelity simulations of head impact experienced by the TBI subject using the Sandia head-neck-torso model and the shock physics computer code CTH. Intracranial fluid cavitation predictions were compared with maps of DTI fractional anisotropy and fMRI hypoactivity to assess whether a possible correlation exists. The ultimate goal of this work is to assess whether one can correlate simulation predictions of intracranial fluid cavitation with the brain injured sites identified by the fMRI and DTI analyses. The outcome of this effort is described in this report.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2022

A Bioinspired Artificial Injury Response System Based on a Robust Polymer Memristor to Mimic a Sense of Pain, Sign of Injury, and Healing

Abstract Flexible electronic skin with features that include sensing, processing, and responding to stimuli have transformed human–robot interactions. However, more advanced capabilities, such as human‐like self‐protection modalities with a sense of pain, sign of injury, and healing, are more challenging. Herein, a novel, flexible, and robust diffusive memristor based on a copolymer of chlorotrifluoroethylene and vinylidene fluoride (FK‐800) as an artificial nociceptor (pain sensor) is reported. Devices composed of Ag/FK‐800/Pt have outstanding switching endurance >10 6 cycles, orders of magnitude higher than any other two‐terminal polymer/organic memristors in literature (typically 10 2 –10 3 cycles). In situ conductive atomic force microscopy is employed to dynamically switch individual filaments, which demonstrates that conductive filaments correlate with polymer grain boundaries and FK‐800 has superior morphological stability under repeated switching cycles. It is hypothesized that the high thermal stability and high elasticity of FK‐800 contribute to the stability under local Joule heating associated with electrical switching. To mimic biological nociceptors, four signature nociceptive characteristics are demonstrated: threshold triggering, no adaptation, relaxation, and sensitization. Lastly, by integrating a triboelectric generator (artificial mechanoreceptor), memristor (artificial nociceptor), and light emitting diode (artificial bruise), the first bioinspired injury response system capable of sensing pain, showing signs of injury, and healing, is demonstrated.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Knockout of CNR1 prevents metabolic stress-induced cardiac injury through improving insulin resistance (IR) injury and endoplasmic reticulum (ER) stress by promoting AMPK-alpha activation

Highlights: • CNR1 knockout attenuates insulin resistance in HFD-fed mice. • CNR1 deletion could attenuate HFD-induced cardiac dysfunction and injury. • CNR1 deficiency attenuates insulin resistance and ER stress in heart of mice fed with HFD. Obesity and diabetes are associated with diabetic cardiomyopathy (DCM). However, the pathogenesis of DCM is not fully understood. Cannabinoid receptor gene (CNR1) has been a drug target for the treatment of obesity. Here, we reported that CNR1 expression was increased in high fat diet (HFD)-induced heart of mice. Following, the wild type (CNR1{sup +/+}) and CNR1-knockout (CNR1{sup −/−}) mice were employed and subjected to HFD treatments for 16 weeks to further investigate the effects of CNR1 on DCM. The results indicated that CNR1 knockout mice after HFD feeding exhibited a significant decrease of body weight and lipid accumulation in serum. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) analysis indicated that HFD-induced insulin resistance was attenuated by CNR1 deficiency. HFD-triggered cardiac dysfunction was also improved by CNR1 knockout using echocardiographic analysis. Further, CNR1 suppression increased expressions of genes promoting fatty acid oxidation, and mitochondrial biogenesis. Also, TUNEL staining showed that CNR1 inhibition markedly reduced apoptotic levels in heart tissue sections of HFD-fed mice. Importantly, HFD-induced insulin resistance was prevented by CNR1-knockout through decreasing p-IRS1{sup Ser} expressions, and increasing phosphorylated insulin receptor substrate 1 (p-IRS1{sup Tyr}), phospho-AMP-activated protein kinase α (AMPKα) and phospho-acetyl-CoA carboxylase α (ACCα) expressions in heart tissue samples. In addition, CNR1 knockout impeded endoplasmic reticulum (ER) stress caused by HFD via down-regulating phospho-protein kinase-like ER kinase (PERK), phospho-eukaryotic initiation factor-2α (eIF2α), activating transcription factor 4 (ATF4) and ATF6 in heart tissue samples. Of note, we found that CNR1 knockout-improved insulin resistance, ER stress and lipid accumulation was diminished by AMPKα suppression using its inhibitor, Compound C. Therefore, the results demonstrated that therapeutic CNR1 inhibition could alleviate the progression of DCM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury

The signaling of cells by scaffolds of synthetic molecules that mimic proteins is known to be effective in the regeneration of tissues. Here, we describe peptide amphiphile supramolecular polymers containing two distinct signals and test them in a mouse model of severe spinal cord injury. One signal activates the transmembrane receptor β1-integrin and a second one activates the basic fibroblast growth factor 2 receptor. By mutating the peptide sequence of the amphiphilic monomers in nonbioactive domains, we intensified the motions of molecules within scaffold fibrils. This resulted in notable differences in vascular growth, axonal regeneration, myelination, survival of motor neurons, reduced gliosis, and functional recovery. Here, we hypothesize that the signaling of cells by ensembles of molecules could be optimized by tuning their internal motions.

36 MATERIALS SCIENCE↗