Pub Date : 2019-10-03eCollection Date: 2019-01-01DOI: 10.1186/s42490-019-0025-9
Farouk Chrif, Tobias Nef, Kenneth J Hunt
Background: Leg-press devices are one of the most widely used training tools for musculoskeletal strengthening of the lower-limbs, and have demonstrated important cardiopulmonary benefits for healthy and patient populations. Further engineering development was done on a dynamic leg-press for work-rate estimation by integrating force and motion sensors, power calculation and a visual feedback system for volitional work-rate control. This study aimed to assess the feasibility of the enhanced dynamic leg press for cardiopulmonary exercise training in constant-load training and high-intensity interval training. Five healthy participants aged 31.0±3.9 years (mean ± standard deviation) performed two cardiopulmonary training sessions: constant-load training and high-intensity interval training. Participants carried out the training sessions at a work rate that corresponds to their first ventilatory threshold for constant-load training, and their second ventilatory threshold for high-intensity interval training.
Results: All participants tolerated both training protocols, and could complete the training sessions with no complications. Substantial cardiopulmonary responses were observed. The difference between mean oxygen uptake and target oxygen uptake was 0.07±0.34 L/min (103 ±17%) during constant-load training, and 0.35±0.66 L/min (113 ±27%) during high-intensity interval training. The difference between mean heart rate and target heart rate was -7±19 bpm (94 ±15%) during constant-load training, and 4.2±16 bpm (103 ±12%) during high-intensity interval training.
Conclusions: The enhanced dynamic leg press was found to be feasible for cardiopulmonary exercise training, and for exercise prescription for different training programmes based on the ventilatory thresholds.
{"title":"Technical feasibility of constant-load and high-intensity interval training for cardiopulmonary conditioning using a re-engineered dynamic leg press.","authors":"Farouk Chrif, Tobias Nef, Kenneth J Hunt","doi":"10.1186/s42490-019-0025-9","DOIUrl":"10.1186/s42490-019-0025-9","url":null,"abstract":"<p><strong>Background: </strong>Leg-press devices are one of the most widely used training tools for musculoskeletal strengthening of the lower-limbs, and have demonstrated important cardiopulmonary benefits for healthy and patient populations. Further engineering development was done on a dynamic leg-press for work-rate estimation by integrating force and motion sensors, power calculation and a visual feedback system for volitional work-rate control. This study aimed to assess the feasibility of the enhanced dynamic leg press for cardiopulmonary exercise training in constant-load training and high-intensity interval training. Five healthy participants aged 31.0±3.9 years (mean ± standard deviation) performed two cardiopulmonary training sessions: constant-load training and high-intensity interval training. Participants carried out the training sessions at a work rate that corresponds to their first ventilatory threshold for constant-load training, and their second ventilatory threshold for high-intensity interval training.</p><p><strong>Results: </strong>All participants tolerated both training protocols, and could complete the training sessions with no complications. Substantial cardiopulmonary responses were observed. The difference between mean oxygen uptake and target oxygen uptake was 0.07±0.34 L/min (103 ±17%) during constant-load training, and 0.35±0.66 L/min (113 ±27%) during high-intensity interval training. The difference between mean heart rate and target heart rate was -7±19 bpm (94 ±15%) during constant-load training, and 4.2±16 bpm (103 ±12%) during high-intensity interval training.</p><p><strong>Conclusions: </strong>The enhanced dynamic leg press was found to be feasible for cardiopulmonary exercise training, and for exercise prescription for different training programmes based on the ventilatory thresholds.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"26"},"PeriodicalIF":0.0,"publicationDate":"2019-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38357696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-26eCollection Date: 2019-01-01DOI: 10.1186/s42490-019-0023-y
Mingjia Du, Baohua Hu, Feiyun Xiao, Ming Wu, Zongjun Zhu, Yong Wang
Background: Accurate spasticity assessment provides an objective evaluation index for the rehabilitation treatment of patients with spasticity, and the key is detecting stretch reflex onset. The surface electromyogram of patients with spasticity is prone to false peaks, and its data length is unstable. These conditions decrease signal differences before and after stretch reflex onset. Therefore, a method for detecting stretch reflex onset based on empirical mode decomposition denoising and modified sample entropy recognition is proposed in this study.
Results: The empirical mode decomposition algorithm is better than the wavelet threshold algorithm in denoising surface electromyogram signal. Without adding Gaussian white noise to the electromyogram signal, the stretch reflex onset recognition rate of the electromyogram signal before and after empirical mode decomposition denoising was increased by 56%. In particular, the recognition rate of stretch reflex onset under the optimal parameter of the modified sample entropy can reach up to 100% and the average recognition rate is 93%.
Conclusions: The empirical mode decomposition algorithm can eliminate the baseline activity of the surface electromyogram signal before stretch reflex onset and effectively remove noise from the signal. The identification of stretch reflex onset using combined empirical mode decomposition and modified sample entropy is better than that via modified sample entropy alone, and stretch reflex onset can be accurately determined.
{"title":"Detection of stretch reflex onset based on empirical mode decomposition and modified sample entropy.","authors":"Mingjia Du, Baohua Hu, Feiyun Xiao, Ming Wu, Zongjun Zhu, Yong Wang","doi":"10.1186/s42490-019-0023-y","DOIUrl":"10.1186/s42490-019-0023-y","url":null,"abstract":"<p><strong>Background: </strong>Accurate spasticity assessment provides an objective evaluation index for the rehabilitation treatment of patients with spasticity, and the key is detecting stretch reflex onset. The surface electromyogram of patients with spasticity is prone to false peaks, and its data length is unstable. These conditions decrease signal differences before and after stretch reflex onset. Therefore, a method for detecting stretch reflex onset based on empirical mode decomposition denoising and modified sample entropy recognition is proposed in this study.</p><p><strong>Results: </strong>The empirical mode decomposition algorithm is better than the wavelet threshold algorithm in denoising surface electromyogram signal. Without adding Gaussian white noise to the electromyogram signal, the stretch reflex onset recognition rate of the electromyogram signal before and after empirical mode decomposition denoising was increased by 56%. In particular, the recognition rate of stretch reflex onset under the optimal parameter of the modified sample entropy can reach up to 100% and the average recognition rate is 93%.</p><p><strong>Conclusions: </strong>The empirical mode decomposition algorithm can eliminate the baseline activity of the surface electromyogram signal before stretch reflex onset and effectively remove noise from the signal. The identification of stretch reflex onset using combined empirical mode decomposition and modified sample entropy is better than that via modified sample entropy alone, and stretch reflex onset can be accurately determined.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2019-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7421583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38454815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-03eCollection Date: 2019-01-01DOI: 10.1186/s42490-019-0022-z
Wing-Kin Tam, Tong Wu, Qi Zhao, Edward Keefer, Zhi Yang
Many people suffer from movement disability due to amputation or neurological diseases. Fortunately, with modern neurotechnology now it is possible to intercept motor control signals at various points along the neural transduction pathway and use that to drive external devices for communication or control. Here we will review the latest developments in human motor decoding. We reviewed the various strategies to decode motor intention from human and their respective advantages and challenges. Neural control signals can be intercepted at various points in the neural signal transduction pathway, including the brain (electroencephalography, electrocorticography, intracortical recordings), the nerves (peripheral nerve recordings) and the muscles (electromyography). We systematically discussed the sites of signal acquisition, available neural features, signal processing techniques and decoding algorithms in each of these potential interception points. Examples of applications and the current state-of-the-art performance were also reviewed. Although great strides have been made in human motor decoding, we are still far away from achieving naturalistic and dexterous control like our native limbs. Concerted efforts from material scientists, electrical engineers, and healthcare professionals are needed to further advance the field and make the technology widely available in clinical use.
{"title":"Human motor decoding from neural signals: a review.","authors":"Wing-Kin Tam, Tong Wu, Qi Zhao, Edward Keefer, Zhi Yang","doi":"10.1186/s42490-019-0022-z","DOIUrl":"10.1186/s42490-019-0022-z","url":null,"abstract":"<p><p>Many people suffer from movement disability due to amputation or neurological diseases. Fortunately, with modern neurotechnology now it is possible to intercept motor control signals at various points along the neural transduction pathway and use that to drive external devices for communication or control. Here we will review the latest developments in human motor decoding. We reviewed the various strategies to decode motor intention from human and their respective advantages and challenges. Neural control signals can be intercepted at various points in the neural signal transduction pathway, including the brain (electroencephalography, electrocorticography, intracortical recordings), the nerves (peripheral nerve recordings) and the muscles (electromyography). We systematically discussed the sites of signal acquisition, available neural features, signal processing techniques and decoding algorithms in each of these potential interception points. Examples of applications and the current state-of-the-art performance were also reviewed. Although great strides have been made in human motor decoding, we are still far away from achieving naturalistic and dexterous control like our native limbs. Concerted efforts from material scientists, electrical engineers, and healthcare professionals are needed to further advance the field and make the technology widely available in clinical use.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2019-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42490-019-0022-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38358001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-30eCollection Date: 2019-01-01DOI: 10.1186/s42490-019-0021-0
Juan Trelles Trabucco, Andrea Rottigni, Marco Cavallo, Daniel Bailey, James Patton, G Elisabeta Marai
Background: In virtual reality (VR) applications such as games, virtual training, and interactive neurorehabilitation, one can employ either the first-person user perspective or the third-person perspective to perceive the virtual environment; however, applications rarely offer both perspectives for the same task. We used a targeted-reaching task in a large-scale virtual reality environment (N=30 healthy volunteers) to evaluate the effects of user perspective on the head and upper extremity movements, and on user performance. We further evaluated how different cognitive challenges would modulate these effects. Finally, we obtained the user-reported engagement level under the different perspectives.
Results: We found that first-person perspective resulted in larger head movements (3.52±1.3m) than the third-person perspective (2.41±0.7m). First-person perspective also resulted in more upper-extremity movement (30.08±7.28m compared to 26.66±4.86m) and longer completion times (61.3±16.4s compared to 53±10.4s) for more challenging tasks such as the "flipped mode", in which moving one arm causes the opposite virtual arm to move. We observed no significant effect of user perspective alone on the success rate. Subjects reported experiencing roughly the same level of engagement in both first-person and third-person perspectives (F(1.58)=0.9,P=.445).
Conclusion: User perspective and its interaction with higher-cognitive load tasks influences the extent of movement and user performance in a virtual theater environment, and may influence the choice of the interface type (first or third person) in immersive training depending on the user conditions and exercise requirements.
{"title":"User perspective and higher cognitive task-loads influence movement and performance in immersive training environments.","authors":"Juan Trelles Trabucco, Andrea Rottigni, Marco Cavallo, Daniel Bailey, James Patton, G Elisabeta Marai","doi":"10.1186/s42490-019-0021-0","DOIUrl":"https://doi.org/10.1186/s42490-019-0021-0","url":null,"abstract":"<p><strong>Background: </strong>In virtual reality (VR) applications such as games, virtual training, and interactive neurorehabilitation, one can employ either the first-person user perspective or the third-person perspective to perceive the virtual environment; however, applications rarely offer both perspectives for the same task. We used a targeted-reaching task in a large-scale virtual reality environment (<i>N</i>=30 healthy volunteers) to evaluate the effects of user perspective on the head and upper extremity movements, and on user performance. We further evaluated how different cognitive challenges would modulate these effects. Finally, we obtained the user-reported engagement level under the different perspectives.</p><p><strong>Results: </strong>We found that first-person perspective resulted in larger head movements (3.52±1.3<i>m</i>) than the third-person perspective (2.41±0.7<i>m</i>). First-person perspective also resulted in more upper-extremity movement (30.08±7.28<i>m</i> compared to 26.66±4.86<i>m</i>) and longer completion times (61.3±16.4<i>s</i> compared to 53±10.4<i>s</i>) for more challenging tasks such as the \"flipped mode\", in which moving one arm causes the opposite virtual arm to move. We observed no significant effect of user perspective alone on the success rate. Subjects reported experiencing roughly the same level of engagement in both first-person and third-person perspectives (<i>F</i>(1.58)=0.9,<i>P</i>=.445).</p><p><strong>Conclusion: </strong>User perspective and its interaction with higher-cognitive load tasks influences the extent of movement and user performance in a virtual theater environment, and may influence the choice of the interface type (first or third person) in immersive training depending on the user conditions and exercise requirements.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2019-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42490-019-0021-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38456104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-22eCollection Date: 2019-01-01DOI: 10.1186/s42490-019-0020-1
Chanwit Phongamwong, Philip Rowe, Karen Chase, Andrew Kerr, Lindsay Millar
Background: Stroke rehabilitation often uses the motor relearning concept that require patients to perform active practice of skill-specific training and to receive feedback. Treadmill training augmented with real-time visualisation feedback and functional electrical stimulation may have a beneficial synergistic effect on motor recovery. This study aims to determine the feasibility of this kind of enhanced treadmill training for gait rehabilitation among patients after stroke. A system for dynamic visualisation of lower-limb movement based on 3-dimentional motion capture and a computer timed functional electrical stimulation system was developed. Participants received up to 20-min enhanced treadmill training instead of their over-ground gait training once or twice a week for 6 weeks at Coathill hospital, Lanarkshire, United Kingdom. Number of training sessions attended, and training duration were used to assess feasibility. Ankle kinematics in the sagittal plane of walking with and without functional electrical stimulation support of the pre-tibial muscles were also compared and used to confirm the functional electrical stimulation was triggered at the targeted time.
Results: Six patients after stroke participated in the study. The majority of participants were male (5/6) with a age range from 30 to 84 years and 4/6 had left hemiplegia. All participants suffered from brain infarction and were at least 3 months after stroke. Number of training sessions attended ranged from 5 to 12. The duration of training sessions ranged from 11 to 20 min. No serious adverse events were reported. The computerised functional electrical stimulation to the pre-tibial muscles was able to reduce plantarflexion angle during the swing phase with statistical significance (p = 0.015 at 80%; p = 0.008 at 90 and 100% of the gait cycle).
Conclusions: It is safe and feasible to use treadmill gait training augmented with real-time visual feedback and computer-controlled functional electrical stimulation with patients after stroke in routine clinical practice.
Trial registration: NCT03348215. Registered 20 November 2017.
{"title":"Treadmill training augmented with real-time visualisation feedback and function electrical stimulation for gait rehabilitation after stroke: a feasibility study.","authors":"Chanwit Phongamwong, Philip Rowe, Karen Chase, Andrew Kerr, Lindsay Millar","doi":"10.1186/s42490-019-0020-1","DOIUrl":"https://doi.org/10.1186/s42490-019-0020-1","url":null,"abstract":"<p><strong>Background: </strong>Stroke rehabilitation often uses the motor relearning concept that require patients to perform active practice of skill-specific training and to receive feedback. Treadmill training augmented with real-time visualisation feedback and functional electrical stimulation may have a beneficial synergistic effect on motor recovery. This study aims to determine the feasibility of this kind of enhanced treadmill training for gait rehabilitation among patients after stroke. A system for dynamic visualisation of lower-limb movement based on 3-dimentional motion capture and a computer timed functional electrical stimulation system was developed. Participants received up to 20-min enhanced treadmill training instead of their over-ground gait training once or twice a week for 6 weeks at Coathill hospital, Lanarkshire, United Kingdom. Number of training sessions attended, and training duration were used to assess feasibility. Ankle kinematics in the sagittal plane of walking with and without functional electrical stimulation support of the pre-tibial muscles were also compared and used to confirm the functional electrical stimulation was triggered at the targeted time.</p><p><strong>Results: </strong>Six patients after stroke participated in the study. The majority of participants were male (5/6) with a age range from 30 to 84 years and 4/6 had left hemiplegia. All participants suffered from brain infarction and were at least 3 months after stroke. Number of training sessions attended ranged from 5 to 12. The duration of training sessions ranged from 11 to 20 min. No serious adverse events were reported. The computerised functional electrical stimulation to the pre-tibial muscles was able to reduce plantarflexion angle during the swing phase with statistical significance (<i>p</i> = 0.015 at 80%; <i>p</i> = 0.008 at 90 and 100% of the gait cycle).</p><p><strong>Conclusions: </strong>It is safe and feasible to use treadmill gait training augmented with real-time visual feedback and computer-controlled functional electrical stimulation with patients after stroke in routine clinical practice.</p><p><strong>Trial registration: </strong>NCT03348215. Registered 20 November 2017.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42490-019-0020-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38454818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-08eCollection Date: 2019-01-01DOI: 10.1186/s42490-019-0019-7
John T Ramshur, Bashir I Morshed, Amy L de Jongh Curry, Robert S Waters
Background: A growing need exists for neuroscience platforms that can perform simultaneous chronic recording and stimulation of neural tissue in animal models in a telemetry-controlled fashion with signal processing for analysis of the chronic recording data and external triggering capability. We describe the system design, testing, evaluation, and implementation of a wireless simultaneous stimulation-and-recording device (SRD) for modulating cortical circuits in physiologically identified sites in primary somatosensory (SI) cortex in awake-behaving and freely-moving rats. The SRD was developed using low-cost electronic components and open-source software. The function of the SRD was assessed by bench and in-vivo testing.
Results: The SRD recorded spontaneous spiking and bursting neuronal activity, evoked responses to programmed intracortical microstimulation (ICMS) delivered internally by the SRD, and evoked responses to external peripheral forelimb stimulation.
Conclusions: The SRD is capable of wireless stimulation and recording on a predetermined schedule or can be wirelessly synchronized with external input as would be required in behavioral testing prior to, during, and following ICMS.
{"title":"Telemetry-controlled simultaneous stimulation-and-recording device (SRD) to study interhemispheric cortical circuits in rat primary somatosensory (SI) cortex.","authors":"John T Ramshur, Bashir I Morshed, Amy L de Jongh Curry, Robert S Waters","doi":"10.1186/s42490-019-0019-7","DOIUrl":"https://doi.org/10.1186/s42490-019-0019-7","url":null,"abstract":"<p><strong>Background: </strong>A growing need exists for neuroscience platforms that can perform simultaneous chronic recording and stimulation of neural tissue in animal models in a telemetry-controlled fashion with signal processing for analysis of the chronic recording data and external triggering capability. We describe the system design, testing, evaluation, and implementation of a wireless simultaneous stimulation-and-recording device (SRD) for modulating cortical circuits in physiologically identified sites in primary somatosensory (SI) cortex in awake-behaving and freely-moving rats. The SRD was developed using low-cost electronic components and open-source software. The function of the SRD was assessed by bench and in-vivo testing.</p><p><strong>Results: </strong>The SRD recorded spontaneous spiking and bursting neuronal activity, evoked responses to programmed intracortical microstimulation (ICMS) delivered internally by the SRD, and evoked responses to external peripheral forelimb stimulation.</p><p><strong>Conclusions: </strong>The SRD is capable of wireless stimulation and recording on a predetermined schedule or can be wirelessly synchronized with external input as would be required in behavioral testing prior to, during, and following ICMS.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2019-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42490-019-0019-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38358686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Organoids derived from induced pluripotent stem (iPS) or embryonic stem (ES) cells have been evaluated as in vitro models of development and disease. However, maintaining these cells under long-term static culture conditions is difficult because of nutrition shortages and waste accumulation. To overcome these issues, perfusion culture systems are required for organoid technology. A system with a stable microenvironment, nutrient availability, and waste removal will accelerate organoid generation. The aim of this study was to develop a novel perfusion system for renal organoids by maintaining the air-liquid interface with a device fabricated using a 3D printer.
Results: Our results revealed slow flow at the organoid cultivation area based on microbead movement on the membrane, which depended on the perfusion rate under the membrane. Moreover, the perfused culture medium below the organoids via a porous membrane diffused throughout the organoids, maintaining the air-liquid interface. The diffusion rates within organoids were increased according to the flow rate of the culture medium under the membrane. The perfused culture medium also stimulated cytoskeletal and basement membrane re-organization associated with promotion tubular formation under 2.5 μL/min flow culture. In contrast, tubules in organoids were diminished at a flow rate of 10 μL/min.
Conclusions: Our liquid-air interface perfusion system accelerated organization of the renal organoids. These results suggest that suitable perfusion conditions can accelerate organization of epithelial cells and tissues in renal organoids in vitro.
{"title":"Perfusion culture maintained with an air-liquid interface to stimulate epithelial cell organization in renal organoids in vitro.","authors":"Sachiko Sekiya, Tetsutaro Kikuchi, Tatsuya Shimizu","doi":"10.1186/s42490-019-0017-9","DOIUrl":"https://doi.org/10.1186/s42490-019-0017-9","url":null,"abstract":"<p><strong>Background: </strong>Organoids derived from induced pluripotent stem (iPS) or embryonic stem (ES) cells have been evaluated as in vitro models of development and disease. However, maintaining these cells under long-term static culture conditions is difficult because of nutrition shortages and waste accumulation. To overcome these issues, perfusion culture systems are required for organoid technology. A system with a stable microenvironment, nutrient availability, and waste removal will accelerate organoid generation. The aim of this study was to develop a novel perfusion system for renal organoids by maintaining the air-liquid interface with a device fabricated using a 3D printer.</p><p><strong>Results: </strong>Our results revealed slow flow at the organoid cultivation area based on microbead movement on the membrane, which depended on the perfusion rate under the membrane. Moreover, the perfused culture medium below the organoids via a porous membrane diffused throughout the organoids, maintaining the air-liquid interface. The diffusion rates within organoids were increased according to the flow rate of the culture medium under the membrane. The perfused culture medium also stimulated cytoskeletal and basement membrane re-organization associated with promotion tubular formation under 2.5 μL/min flow culture. In contrast, tubules in organoids were diminished at a flow rate of 10 μL/min.</p><p><strong>Conclusions: </strong>Our liquid-air interface perfusion system accelerated organization of the renal organoids. These results suggest that suitable perfusion conditions can accelerate organization of epithelial cells and tissues in renal organoids in vitro.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2019-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42490-019-0017-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38358679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-17eCollection Date: 2019-01-01DOI: 10.1186/s42490-019-0018-8
Hanneke N Monsuur, Ester M Weijers, Susan Gibbs, Lenie J van den Broek
Background: Therapy resistant ulcers are wounds that remain open for a long time period and often arise from chronic venous disease, prolonged pressure or diabetes. For healing of chronic wounds, revitalization of the inert wound bed, which is achieved by angiogenic sprouting of new blood vessels is of great importance. An alternative treatment option to conventional therapies is the use of skin substitutes: dermal (DS), epidermal (ES) or bi-layered skin substitutes (SS). The aim of this study was to determine the mode of action of an autologous SS, ES and DS with regards to endothelial cell proliferation, migration and angiogenic sprouting into a fibrin hydrogel.
Results: SS consists of a fully differentiated epidermis expanding over the acellular donor dermis (AD) which has become repopulated with fibroblasts. DS is the same construct as SS but without the epidermis and ES is the same construct as SS but without the fibroblasts. As a control, AD was used throughout. It was found that the bi-layered SS was the most potent substitute in inducing migration and sprouting of endothelial cells. The cross talk between dermis and epidermis resulted in the strongest induction of sprouting via VEGF and uPAR. ES stimulated sprouting more than DS again via VEGF and uPAR. The slight induction of sprouting mediated by DS was not mediated by VEGF, but was in part stimulated through uPAR.
Conclusion: This in vitro study supports our clinical observations that a bi-layered SS is a strong stimulator of angiogenesis and therefore has the potential to revitalize an inert wound bed.
{"title":"Skin substitutes are more potent than dermal or epidermal substitutes in stimulating endothelial cell sprouting.","authors":"Hanneke N Monsuur, Ester M Weijers, Susan Gibbs, Lenie J van den Broek","doi":"10.1186/s42490-019-0018-8","DOIUrl":"https://doi.org/10.1186/s42490-019-0018-8","url":null,"abstract":"<p><strong>Background: </strong>Therapy resistant ulcers are wounds that remain open for a long time period and often arise from chronic venous disease, prolonged pressure or diabetes. For healing of chronic wounds, revitalization of the inert wound bed, which is achieved by angiogenic sprouting of new blood vessels is of great importance. An alternative treatment option to conventional therapies is the use of skin substitutes: dermal (DS), epidermal (ES) or bi-layered skin substitutes (SS). The aim of this study was to determine the mode of action of an autologous SS, ES and DS with regards to endothelial cell proliferation, migration and angiogenic sprouting into a fibrin hydrogel.</p><p><strong>Results: </strong>SS consists of a fully differentiated epidermis expanding over the acellular donor dermis (AD) which has become repopulated with fibroblasts. DS is the same construct as SS but without the epidermis and ES is the same construct as SS but without the fibroblasts. As a control, AD was used throughout. It was found that the bi-layered SS was the most potent substitute in inducing migration and sprouting of endothelial cells. The cross talk between dermis and epidermis resulted in the strongest induction of sprouting via VEGF and uPAR. ES stimulated sprouting more than DS again via VEGF and uPAR. The slight induction of sprouting mediated by DS was not mediated by VEGF, but was in part stimulated through uPAR.</p><p><strong>Conclusion: </strong>This in vitro study supports our clinical observations that a bi-layered SS is a strong stimulator of angiogenesis and therefore has the potential to revitalize an inert wound bed.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2019-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42490-019-0018-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38359788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-01eCollection Date: 2019-01-01DOI: 10.1186/s42490-019-0016-x
JinWoo Hong, Chae-Ok Yun
Adenovirus (Ad) has been most extensively evaluated gene transfer vector in clinical trials due to facile production in high viral titer, highly efficient transduction, and proven safety record. Similarly, an oncolytic Ad, which replicates selectively in cancer cells through genetic modifications, is actively being evaluated in various phases of clinical trials as a promising next generation therapeutic against cancer. Most of these trials with oncolytic Ads to date have employed intratumoral injection as the standard administration route. Although these locally administered oncolytic Ads have shown promising outcomes, the therapeutic efficacy is not yet optimal due to poor intratumoral virion retention, nonspecific shedding of virion to normal organs, variable infection efficacy due to heterogeneity of tumor cells, adverse antiviral immune response, and short biological activity of oncolytic viruses in situ. These inherent problems associated with locally administered Ad also holds true for other oncolytic viral vectors. Thus, this review will aim to discuss various nanomaterial-based delivery strategies to improve the intratumoral administration efficacy of oncolytic Ad as well as other types of oncolytic viruses.
{"title":"Overcoming the limitations of locally administered oncolytic virotherapy.","authors":"JinWoo Hong, Chae-Ok Yun","doi":"10.1186/s42490-019-0016-x","DOIUrl":"https://doi.org/10.1186/s42490-019-0016-x","url":null,"abstract":"<p><p>Adenovirus (Ad) has been most extensively evaluated gene transfer vector in clinical trials due to facile production in high viral titer, highly efficient transduction, and proven safety record. Similarly, an oncolytic Ad, which replicates selectively in cancer cells through genetic modifications, is actively being evaluated in various phases of clinical trials as a promising next generation therapeutic against cancer. Most of these trials with oncolytic Ads to date have employed intratumoral injection as the standard administration route. Although these locally administered oncolytic Ads have shown promising outcomes, the therapeutic efficacy is not yet optimal due to poor intratumoral virion retention, nonspecific shedding of virion to normal organs, variable infection efficacy due to heterogeneity of tumor cells, adverse antiviral immune response, and short biological activity of oncolytic viruses in situ. These inherent problems associated with locally administered Ad also holds true for other oncolytic viral vectors. Thus, this review will aim to discuss various nanomaterial-based delivery strategies to improve the intratumoral administration efficacy of oncolytic Ad as well as other types of oncolytic viruses.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42490-019-0016-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38359423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-28eCollection Date: 2019-01-01DOI: 10.1186/s42490-019-0014-z
Robert B Good, Jessica D Eley, Elaine Gower, Genevieve Butt, Andrew D Blanchard, Andrew J Fisher, Carmel B Nanthakumar
Background: Excessive extracellular matrix (ECM) deposition is a hallmark feature in fibrosis and tissue remodelling diseases. Typically, mesenchymal cells will produce collagens under standard 2D cell culture conditions, however these do not assemble into fibrils. Existing assays for measuring ECM production are often low throughput and not disease relevant. Here we describe a robust, high content, pseudo-3D phenotypic assay to quantify mature fibrillar collagen deposition which is both physiologically relevant and amenable to high throughput compound screening. Using pulmonary fibroblasts derived from patients with idiopathic pulmonary fibrosis (IPF), we developed the 'scar-in-a-jar' assay into a medium-throughput phenotypic assay to robustly quantify collagen type I deposition and other extracellular matrix (ECM) proteins over 72 h.
Results: This assay utilises macromolecular crowding to induce an excluded volume effect and enhance enzyme activity, which in combination with TGF-β1 stimulation significantly accelerates ECM production. Collagen type I is upregulated approximately 5-fold with a negligible effect on cell number. We demonstrate the robustness of the assay achieving a Z prime of approximately 0.5, and % coefficient of variance (CV) of < 5 for the assay controls SB-525334 (ALK5 inhibitor) and CZ415 (mTOR inhibitor). This assay has been used to confirm the potency of a number of potential anti-fibrotic agents. Active compounds from the 'scar-in-a-jar' assay can be further validated for other markers of ECM deposition and fibroblast activation such as collagen type IV and α-smooth muscle actin exhibiting a 4-fold and 3-fold assay window respectively.
Conclusion: In conclusion, we have developed 'scar -in-a-jar is' into a robust disease-relevant medium-throughput in vitro assay to accurately quantify ECM deposition. This assay may enable iterative compound profiling for IPF and other fibroproliferative and tissue remodelling diseases.
{"title":"A high content, phenotypic 'scar-in-a-jar' assay for rapid quantification of collagen fibrillogenesis using disease-derived pulmonary fibroblasts.","authors":"Robert B Good, Jessica D Eley, Elaine Gower, Genevieve Butt, Andrew D Blanchard, Andrew J Fisher, Carmel B Nanthakumar","doi":"10.1186/s42490-019-0014-z","DOIUrl":"10.1186/s42490-019-0014-z","url":null,"abstract":"<p><strong>Background: </strong>Excessive extracellular matrix (ECM) deposition is a hallmark feature in fibrosis and tissue remodelling diseases. Typically, mesenchymal cells will produce collagens under standard 2D cell culture conditions, however these do not assemble into fibrils. Existing assays for measuring ECM production are often low throughput and not disease relevant. Here we describe a robust, high content, pseudo-3D phenotypic assay to quantify mature fibrillar collagen deposition which is both physiologically relevant and amenable to high throughput compound screening. Using pulmonary fibroblasts derived from patients with idiopathic pulmonary fibrosis (IPF), we developed the 'scar-in-a-jar' assay into a medium-throughput phenotypic assay to robustly quantify collagen type I deposition and other extracellular matrix (ECM) proteins over 72 h.</p><p><strong>Results: </strong>This assay utilises macromolecular crowding to induce an excluded volume effect and enhance enzyme activity, which in combination with TGF-β<sub>1</sub> stimulation significantly accelerates ECM production. Collagen type I is upregulated approximately 5-fold with a negligible effect on cell number. We demonstrate the robustness of the assay achieving a Z prime of approximately 0.5, and % coefficient of variance (CV) of < 5 for the assay controls SB-525334 (ALK5 inhibitor) and CZ415 (mTOR inhibitor). This assay has been used to confirm the potency of a number of potential anti-fibrotic agents. Active compounds from the 'scar-in-a-jar' assay can be further validated for other markers of ECM deposition and fibroblast activation such as collagen type IV and α-smooth muscle actin exhibiting a 4-fold and 3-fold assay window respectively.</p><p><strong>Conclusion: </strong>In conclusion, we have developed 'scar -in-a-jar is' into a robust disease-relevant medium-throughput in vitro assay to accurately quantify ECM deposition. This assay may enable iterative compound profiling for IPF and other fibroproliferative and tissue remodelling diseases.</p>","PeriodicalId":72425,"journal":{"name":"BMC biomedical engineering","volume":"1 ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2019-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38357695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}