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19 pages, 5684 KiB  
Article
A Versatile and Modular Microfluidic System for Dynamic Cell Culture and Cellular Interactions
by Qasem Ramadan, Rana Hazaymeh and Mohammed Zourob
Micromachines 2025, 16(2), 237; https://doi.org/10.3390/mi16020237 - 19 Feb 2025
Abstract
A versatile and modular microfluidic system for cell co-culture has been developed. Microfluidic chips, each featuring dual compartments separated by a porous membrane, have been fabricated and assembled within the system to facilitate fluidic interconnection and cell–cell communication through the chip assembly. A [...] Read more.
A versatile and modular microfluidic system for cell co-culture has been developed. Microfluidic chips, each featuring dual compartments separated by a porous membrane, have been fabricated and assembled within the system to facilitate fluidic interconnection and cell–cell communication through the chip assembly. A set of fluidic valves has been successfully integrated to regulate the flow through the chip assembly. The system allows for chip assembly in various arrangements, including in parallel, in series, and complex connections. Individual chips can be interconnected or disconnected within the system at any time. Moreover, the spatial order and orientation of the chips can be adjusted as needed, enabling the study of different cell–cell arrangements and the impact of the presence or absence of specific cell types. The utility of the system has been evaluated by culturing and interconnecting multi-monolayers of intestinal epithelial cells as a model of the complex cellular system. Epithelial monolayers were grown in multiple chips and interconnected in various configurations. The transepithelial electrical resistance and permeability profiles were investigated in detail for these configurations upon treatment of the cells with dextran sulfate sodium. Immune cells were stimulated through the epithelial layers and the expression of inflammatory cytokines was detected. This miniaturized platform offers controlled conditions for co-culturing key cellular components and assessing potential therapeutic agents in a physiologically relevant setting. Full article
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Figure 1
<p>(<b>a</b>) Linking multi-organ models in one fluidic system. Each organ model can be hosted in an individual chip, and the chips can be fluidically connected to allow paracrine/endocrine signaling, mimicking the organ–organ crosstalk in vivo. (<b>b</b>) Schematic representation of the system with six chips connected through a set of valves. An enlarged view of a single chip which comprises two chambers (upper/apical and lower/basolateral) separated by a porous membrane. (<b>c</b>) 2D view of the connected chips, each hosting an in vitro model with the valving modules that enable custom linking of two or more chips in various configurations.</p>
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<p>(<b>a</b>) Linking multi-organ models in one fluidic system. Each organ model can be hosted in an individual chip, and the chips can be fluidically connected to allow paracrine/endocrine signaling, mimicking the organ–organ crosstalk in vivo. (<b>b</b>) Schematic representation of the system with six chips connected through a set of valves. An enlarged view of a single chip which comprises two chambers (upper/apical and lower/basolateral) separated by a porous membrane. (<b>c</b>) 2D view of the connected chips, each hosting an in vitro model with the valving modules that enable custom linking of two or more chips in various configurations.</p>
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<p>(<b>a</b>) The microfluidic chip was fabricated using PMMA using laser machining. Before cutting, one half of the PMMA sheet was laminated with a double-sided adhesive tape to facilitate the bonding of the four layers together. (<b>b</b>) Top view of the four layers with the fluidic chambers’ dimensions. (<b>c</b>) The assembly of the four layers with the porous membrane to form the chips. (<b>d</b>) Optical images of the assembled chips with colored liquid injected to enhance visualization. (<b>e</b>) The design of the fundamental unit incorporates multi-directional fluidic connection gates and integrated electrodes for measuring TEER. (<b>f</b>) A detailed view of the base unit with the chip inserted in. (<b>g</b>) Three different chip assemblies: in parallel, in series, and mix mode.</p>
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<p>(<b>a</b>) Six chips connected in parallel where all the apical compartments are linked together by the two-way valves and, similarly, the basolateral compartments are linked together. Side view (top panel), top view (middle panel), and assembly image (bottom panel). The tracer transport profile within the downstream apical compartments (<b>b</b>) and basolateral compartments (<b>c</b>). The concentration profile exhibits a gradual decline in the downstream compartments. (<b>d</b>) Three chips are interconnected in series. In this arrangement, the basolateral compartment of the first chip is connected to the apical compartment of the next chip. (<b>e</b>) The concentration profile exhibits a gradual decline in the downstream compartments. (<b>f</b>) A complex assembly with six chips is interconnected in a mix mode, combining both series and parallel connections. (<b>g</b>) The corresponding tracer transport profile. * <span class="html-italic">p</span> &lt; 0.1.</p>
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<p>(<b>a</b>) Caco-2 cells were seeded in three identical chips with no interconnection. (<b>b</b>) Optical image of the confluent monolayers within the three chips. (<b>c</b>) TJs formed by adjacent Caco-2 cells. The TJs were stained by FITC-labeled anti-mouse occluding. Images of confluent monolayer formed by Caco-2 cells taken on day 21 under 10× objective lens. (<b>d</b>) TEER values increased progressively over time with a substantial increase observed after 5 days, indicating the presence of the tight junction proteins. (<b>e</b>) Perfusion accelerates the TJ formation and maintains higher TEER value after the formation of the confluent layer. (<b>f</b>) The fluorescence intensity, which corresponds to the concentration of the tracer, exhibited a gradual increase over the 48 h duration.</p>
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<p>(<b>a</b>) The experimental design involved a multi-epithelium structure consisting of three epithelial model chips that were fluidically connected in parallel. The apical compartments of the chips were connected, as were the basolateral compartments. Chip 3 was treated with DSS (5k Da (2%)), and its TEER was examined. Subsequently, chip 3 was detached, and the TEER was assessed again. Following this, chip 2 was subjected to DSS treatment, and its TEER was inspected. Finally, chip 2 was detached, and the TEER for it and for chip 1 were measured. (<b>b</b>) The TEER values for every individual monolayer (EC1, EC2, EC3) and when they are connected (EC1+EC2+EC3) over a 15-day culture period. Both individual layers and connected layers exhibit an increase in TEER over time. While the TEER values for the individual layers are comparable, the TEER of the connected layers slightly surpasses that of the individual layers, notably after one week of culture. (<b>c</b>) When one layer was treated with DSS, the total TEER dropped to approximately 80% of its original value compared to the untreated layer. Upon disconnection/removal of the treated monolayer, the TEER returned to its initial level. Consequently, the TEER values of one, two, or three healthy monolayers were found to be comparable. (<b>d</b>) Cell viability drops upon treating the cells with DSS. * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>The effect of DSS at various concentrations (0.05–5%) on the integrity of the Caco-2 monolayer (TEER). (<b>a</b>) Six Caco-2 monolayers were cultivated on separate chips. Upon reaching confluency, the basolateral compartments of these six chips were interconnected, creating a single large compartment that linked the six apical compartments through the membrane. TEER values exhibited a significant decrease after 24 h of DSS treatment, particularly at higher concentrations of DSS (i.e., 2% and 5%). (<b>b</b>) The EC monolayers were disconnected and the apical-to-basolateral transport (permeability) of FITC-dextran (4 kDa) was measured. The permeability of the EC increases with increasing DSS concentrations. (<b>c</b>) Three chips with fully confluent monolayers were connected in series. The concentration of FITC-dextran decreases in the donor compartment and gradually increases in the downstream compartment. However, the concentration is observed to be maintained at a high value in the chambers along the transportation path during the experiment. (<b>d</b>) The basolateral–apical transport of FITC-dextran was greater than that of apical–basolateral when examined using two individual disconnected chips. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>(<b>a</b>) The experimental design of EC–immune cell co-culture and stimulation. THP-1 monocytic cells were seeded within two separate chips, as illustrated in <a href="#micromachines-16-00237-f007" class="html-fig">Figure 7</a>a. The THP-1 cells within one chip were treated with PMA to induce the differentiation of the cell to adherent macrophages. The THP-1 cells in the other chip (monocyte chip) were kept untreated. An EC monoculture was used as a control setup. (<b>b</b>) The expression of cytokines in the Caco-2/THP-1 and Caco-2/macrophage co-cultures was evaluated relative to levels seen in control Caco-2 epithelial cell monocultures. Macrophages secreted elevated amounts of cytokines when exposed to DSS compared to the THP-1 monocytes. The numbers of THP-1 and macrophage immune cells incorporated into the co-cultures were maintained at comparable levels.</p>
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<p>(<b>a</b>) The experimental design of EC–immune cell co-culture and stimulation. THP-1 monocytic cells were seeded within two separate chips, as illustrated in <a href="#micromachines-16-00237-f007" class="html-fig">Figure 7</a>a. The THP-1 cells within one chip were treated with PMA to induce the differentiation of the cell to adherent macrophages. The THP-1 cells in the other chip (monocyte chip) were kept untreated. An EC monoculture was used as a control setup. (<b>b</b>) The expression of cytokines in the Caco-2/THP-1 and Caco-2/macrophage co-cultures was evaluated relative to levels seen in control Caco-2 epithelial cell monocultures. Macrophages secreted elevated amounts of cytokines when exposed to DSS compared to the THP-1 monocytes. The numbers of THP-1 and macrophage immune cells incorporated into the co-cultures were maintained at comparable levels.</p>
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19 pages, 1229 KiB  
Article
Feasibility of Smartphone-Based Exercise Training Integrated with Functional Electrical Stimulation After Stroke (SETS): A Preliminary Study
by Rudri Purohit, Juan Pablo Appelgren-Gonzalez, Gonzalo Varas-Diaz, Shuaijie Wang, Matias Hosiasson, Felipe Covarrubias-Escudero and Tanvi Bhatt
Sensors 2025, 25(4), 1254; https://doi.org/10.3390/s25041254 - 19 Feb 2025
Abstract
One emerging method in home stroke rehabilitation is digital technology. However, existing approaches typically target one domain (e.g., upper limb). Moreover, existing interventions do not cater to older adults with stroke (OAwS), especially those with high motor impairment, who require adjunct therapeutic agents [...] Read more.
One emerging method in home stroke rehabilitation is digital technology. However, existing approaches typically target one domain (e.g., upper limb). Moreover, existing interventions do not cater to older adults with stroke (OAwS), especially those with high motor impairment, who require adjunct therapeutic agents to independently perform challenging exercises. We examined the feasibility of Smartphone-based Exercise Training after Stroke (SETS) with Functional Electrical Stimulation (FES). A total of 12 participants (67 ± 5 years) with stroke (onset > 6 months) exhibiting moderate-to-high motor impairment (Chedoke McMaster Leg ≤ 4/7) underwent 6 weeks of multicomponent (gait, functional strength, dynamic balance) training integrated with FES to paretic lower limb muscles. Primary measures included safety and adherence. Secondary measures included motivation, acceptability and attitude, usability, and clinical measures of gait and balance function like the 10-Meter Walk Test and Mini-BESTest. Participants reported no adverse events and moderate-to-high adherence (84.17 ± 11.24%) and improvement (up to 40%) in motivation, acceptability, and attitude and system usability. Participants also showed pre-post improvements in all measures of gait and balance function (p < 0.05). Integrating SETS and FES is feasible and yields short-term gains in gait and balance function among OAwS. Future studies could validate our findings by examining its efficacy with control groups to identify the differential effects of SETS and FES. Full article
(This article belongs to the Section Wearables)
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<p>Intervention protocol for SETS (Smartphone Exercise Training after Stroke) with three domains, including dynamic balance, functional strength, and gait. Each component included three levels of exercise progression, examples of which are provided under each domain.</p>
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<p>Box and whisker plots with individual data points for outcomes of gait and balance function. Boxes represent the interquartile ranges (25–75%) of data variance, bold lines within boxes represent the mean, and whiskers represent the standard deviations for (<b>a</b>) Timed-Up and Go test (TUG), measured in seconds; (<b>b</b>) 30-Second Chair Stand Test (30CST), measured in repetitions; (<b>c</b>) 10-Meter Walk Test (10MWT), measured in meters per second; (<b>d</b>) Berg Balance Scale (BBS), scored out of 56; (<b>e</b>) Mini-Balance Evaluation System Test (Mini-BESTest), scored out of 28; and (<b>f</b>) Short Physical Performance Battery (SPPB), scored out of 12 assessed during pre- and post-testing sessions. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.0001.</p>
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15 pages, 732 KiB  
Article
Training Profiles, Efficacy Perceptions, and Outcomes of Non-Invasive Neuromodulation: An Exploratory Study Among Practitioners
by Laura Oliveira Campos, Bianca Rossi Botim, Mayra Evelise Cunha, Denys Batista Campos, Michelle Almeida Barbosa, Gabriela Lopes Gama and Alexandre Carvalho Barbosa
Psychiatry Int. 2025, 6(1), 18; https://doi.org/10.3390/psychiatryint6010018 - 17 Feb 2025
Abstract
Advances in non-invasive neuromodulation (NM) have enabled practitioners to modulate neural activity safely, offering a promising approach to treating neuropsychiatric and neurological conditions. This study aimed to analyze the training profiles of NM practitioners and assess their perceptions of NM’s clinical efficacy, safety, [...] Read more.
Advances in non-invasive neuromodulation (NM) have enabled practitioners to modulate neural activity safely, offering a promising approach to treating neuropsychiatric and neurological conditions. This study aimed to analyze the training profiles of NM practitioners and assess their perceptions of NM’s clinical efficacy, safety, and patient satisfaction. An online survey was conducted among 117 practitioners in various healthcare fields, using the Clinical Global Impression (CGI) scale to gauge outcomes. The findings indicate that 99.13% of practitioners perceive NM as effective, with high rates of patient improvement in quality of life and symptom management. The study underscores the importance of standardized NM training protocols to enhance therapeutic outcomes. Full article
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<p>Training characteristics.</p>
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<p>Adverse effects responses.</p>
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16 pages, 5265 KiB  
Article
The Influence of Empagliflozin on the Expression of Mitochondrial Regulatory Proteins in Human Myocardium in an Ex Vivo Model of Short-Term Atrial Tachypacing
by Paweł Muszyński, Magdalena Cieślińska, Magdalena Dziemidowicz, Elżbieta Bonda-Ostaszewska, Tomasz Hirnle and Tomasz Andrzej Bonda
Int. J. Mol. Sci. 2025, 26(4), 1664; https://doi.org/10.3390/ijms26041664 - 15 Feb 2025
Abstract
Atrial fibrillation (AF) is associated with energetic deficiency and oxidative stress due to mitochondrial dysfunction, resulting in electric remodeling. Long-term treatment was found to ameliorate mitochondrial function and decrease inducibility in animal models. No studies examine the short-term effect of SGLT-2 inhibitors administration [...] Read more.
Atrial fibrillation (AF) is associated with energetic deficiency and oxidative stress due to mitochondrial dysfunction, resulting in electric remodeling. Long-term treatment was found to ameliorate mitochondrial function and decrease inducibility in animal models. No studies examine the short-term effect of SGLT-2 inhibitors administration in AF. In the present study, the samples of the right atrial appendage collected from 10 patients subjected to elective cardiac surgery were sliced and incubated in a control buffer (EMPA 0), 0.2 µmol/L empagliflozin (EMPA 0.2), or 1.0 µmol/L (EMPA 1). The expression of mitochondrial biogenesis, fission, and fusion proteins was measured by Western blot after 30 min of electrical stimulation (control—1 Hz or tachypacing—5 Hz). The PGC-1α protein expression was increased after 30 min of stimulation with 1 Hz when incubated under a higher concentration of empagliflozin. After tachypacing, EMPA 0.2 increased PGC-1α, while EMPA 1.0 upregulated NRF-1. Both concentrations increased NRF-2 during control stimulation. The oxygen consumption was higher in AF, and was decreased by SGLT-2i. Empagliflozin exerts dynamic effects on the expression of PGC-1α and other proteins involved in mitochondrial function and oxidative stress in cardiomyocytes and may modulate cellular response to tachycardia. Full article
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Graphical abstract

Graphical abstract
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<p>Expression level of PGC-1α according to Western blot. * <span class="html-italic">p</span> &lt; 0.05 EMPA 1 µmol/L 1 Hz compared with EMPA 0 µmol/L.</p>
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<p>Expression level of TFAM (<b>a</b>) and OPA-1 (<b>b</b>) according to Western blot.</p>
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<p>The expression level of NRF-1 (<b>a</b>) and NRF-2 (<b>b</b>) according to Western blot. * <span class="html-italic">p</span> &lt; 0.05 EMPA 1 µmol/L 1 Hz compared with EMPA 0 µmol/L.</p>
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<p>The expression level of Drp-1 (<b>a</b>) and Mfn-1 (<b>b</b>) according to Western blot. * <span class="html-italic">p</span> &lt; 0.05 EMPA 1 µmol/L 1 Hz compared with EMPA 0 µmol/L.</p>
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<p>The expression level of CaMKII (<b>a</b>) and SOD-2 (<b>b</b>) according to Western blot.</p>
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<p>Expression level of pCAMKII (<b>a</b>) and relation of pCAMKII to CAMKII (<b>b</b>) according to Western blot.</p>
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<p>Expression level of SIRT3 according to Western blot.</p>
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<p>Expression level of JNK (<b>a</b>) and relation of pJNK (<b>b</b>) according to Western blot.</p>
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<p>Expression level of ERK (<b>a</b>) and relation of pERK (<b>b</b>) according to Western blot.</p>
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<p>Relation of pJNK to JNK (<b>a</b>) and pERK do ERK (<b>b</b>) according to Western blot.</p>
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<p>Oxygen rate after administration of atrial mitochondria (<b>A</b>), after administration of succinate (state 3, complex I  +  II, <b>B</b>), after administration of ADP (state 3, complex I, <b>C</b>), after administration of FCCP (state 3 and state 4, <b>D</b>).</p>
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<p>Comparison of the oxygen consumption.</p>
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<p>Oxygraphy (oxygen consumption rate and oxygen concentration) in ex vivo atrial mitochondria from subjects with AF treated with SGLT-2i.</p>
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<p>Oxygraphy (oxygen consumption rate and oxygen concentration) in ex vivo atrial mitochondria from subjects with AF not treated with SGLT-2i.</p>
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<p>Oxygraphy (oxygen consumption rate and oxygen concentration) in ex vivo atrial mitochondria from subjects without atrial fibrillation not treated with SGLT-2i.</p>
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<p>Oxygraphy (oxygen consumption rate and oxygen concentration) in ex vivo atrial mitochondria from subjects without atrial fibrillation treated with SGLT-2i.</p>
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17 pages, 4553 KiB  
Article
Numerical Simulation of the Effect of Electrical Stimulation on Disuse After Hip Replacement
by Qian Wang, Chuanyong Qu, Xiaohui Li and Yufan Yan
Biomedicines 2025, 13(2), 471; https://doi.org/10.3390/biomedicines13020471 - 14 Feb 2025
Abstract
Background: Total hip replacement replaces the femoral head, which cannot heal, with an artificial femoral shaft to ensure the patient’s normal life. However, due to the stress-masking effect of the proximal femur loaded with the artificial femur stem, the implant bears a large [...] Read more.
Background: Total hip replacement replaces the femoral head, which cannot heal, with an artificial femoral shaft to ensure the patient’s normal life. However, due to the stress-masking effect of the proximal femur loaded with the artificial femur stem, the implant bears a large part of the load, resulting in insufficient stress stimulation of the proximal femur and bone waste remodeling. In turn, it is easy to lose bone, resulting in loosening. As a new treatment method, electrical stimulation has been widely used for bone loss, nonunion, and other diseases, and it has achieved good therapeutic effects. Methods: Therefore, in this work, electrical stimulation was introduced for postoperative density assessment, and a new disuse remodeling model was established to simulate density loss after remodeling and the resistance effect of electrical stimulation. The effects of various parameters on density loss in the model are discussed. Results: The simulation results revealed significant stress masking and density loss in the neck of the femur after hip replacement, and electrical stimulation placed in the neck of the femur may resist this density loss to a certain extent. The rate of bone mineral density reduction decreased after the addition of electrical stimulation, indicating that electrical stimulation can have a certain resistance to the density reduction caused by stress shielding, and this result is helpful for the rehabilitation of hip arthroplasty. Full article
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<p>Finite element model of the femur.</p>
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<p>Density distribution.</p>
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<p>Logical block diagram of the bone-remodeling algorithm.</p>
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<p>Primitive and simplified models of BMU in bone cortex and cancellous bone: (<b>a</b>) the primitive model of BMU in cortical bone; (<b>b</b>) the simplified model of BMU in cortical bone; (<b>c</b>) the primitive model of BMU in cancellous bone; (<b>d</b>) the simplified model of BMU in cancellous bone.</p>
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<p>Stress shadowing cloud map and unit statistics under the standing condition. (<b>a</b>) The boundary conditions; (<b>b</b>) Stress ratio cloud diagram; (<b>c</b>) Statistical histogram of element stress ratio.</p>
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<p>Stress shadowing cloud map and unit statistics under hip abduction conditions. (<b>a</b>) The boundary conditions; (<b>b</b>) Stress ratio cloud diagram; (<b>c</b>) Statistical histogram of element stress ratio.</p>
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<p>Stress shadowing cloud map and unit statistics under hip adduction conditions. (<b>a</b>) The boundary conditions; (<b>b</b>) Stress ratio cloud diagram; (<b>c</b>) Statistical histogram of element stress ratio.</p>
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<p>The overall potential distribution after the charge is applied.</p>
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<p>Normalized potential distribution diagram.</p>
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<p>The variation in cortical bone density and the rate of change in density with time. (<b>a</b>) Density change; (<b>b</b>) The density change rate changes.</p>
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<p>The variation in cancellous bone density and the rate of change in density with time. (<b>a</b>) Density change; (<b>b</b>) The density change rate changes.</p>
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<p>Density difference distribution: (<b>a</b>) without electrical stimulation; (<b>b</b>) electrically stimulated.</p>
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<p>The variation in cortical bone density and the rate of change in density with time. (Add electrical stimulation). (<b>a</b>) Density change; (<b>b</b>) The density change rate changes.</p>
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<p>The variation in cancellous bone density and the rate of change in density with time. (Add electrical stimulation). (<b>a</b>) Density change; (<b>b</b>) The density change rate changes.</p>
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18 pages, 11801 KiB  
Article
Electromagnetic Fields, Electrical Stimulation, and Vacuum Simultaneously Applied for Major Burn Scars
by Salvatore Marafioti, Sheila Veronese, Claudio Pecorella, Carlo Felice Tavernese, Sara Costantino, Maurizio Busoni and Andrea Sbarbati
Bioengineering 2025, 12(2), 179; https://doi.org/10.3390/bioengineering12020179 - 13 Feb 2025
Abstract
Background: Regeneration in the case of major burn subjects must involve tissue and structural regeneration, but also functional regeneration, as scars derived from burns often compromise motility. Electromagnetic fields and electrical stimulation may be a possible treatment for these cases, considering they cause [...] Read more.
Background: Regeneration in the case of major burn subjects must involve tissue and structural regeneration, but also functional regeneration, as scars derived from burns often compromise motility. Electromagnetic fields and electrical stimulation may be a possible treatment for these cases, considering they cause a thermal effect and magneto-mechanical transduction first and selective tissue stimulation second. Methods: A case of a majorly burned woman with severe motor deficits, treated with electromagnetic fields and electrical stimulation in vacuum, associated with a personalized nutritional program, was described. The latter was necessary to favor weight loss with the preservation of the weakened structure. Ultrasonography, Doppler ultrasound, and body composition were measured. Moreover, postural evaluation was performed. Results: Immediately after the treatment, a restructuring of all tissue was seen. After 6 months, the tissue regeneration was evident, with neo-angiogenesis. From the functional point of view, her motility improved, and she stopped using a walker. Conclusions: The combined therapy allows her to obtain unthinkable results in a short time. For this reason, it could become the elective treatment for major burn scars. Full article
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<p>Details of the burns results. (<b>a</b>) Diffuse fibrotic scar on the right forearm; (<b>b</b>) Diffuse fibrotic scar on the left forearm with skin retraction and tissue depression; (<b>c</b>) Both the legs presented severe wide scars, fibrotic areas, skin retraction, areas of tissue depression, keloids, hypertrophic scars, and pigmentation disorders. The aesthetic problems were strictly correlated to functional motor problems.</p>
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<p>Ultrasonography of the forearms at T0. (<b>a</b>) Cicatricial fibrosis (red arrow) of the left forearm involves the whole dermal layer; (<b>b</b>) The inflammation (yellow arrows) is extended down to the deeper layer and, in particular, it involves the surgical grafts (green arrows); (<b>c</b>) Cicatricial fibrosis (red arrow) is also evident on the right side, where the adipose tissue appears inhomogeneous (yellow arrows) and where a cicatricial granuloma is present (white arrow); (<b>d</b>) The aspect described in <a href="#bioengineering-12-00179-f002" class="html-fig">Figure 2</a>c is similar in other areas of the right forearm, where other cicatricial granulomas are present (white arrow).</p>
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<p>Ultrasonography of the forearms at T0. (<b>a</b>) Cicatricial fibrosis (red arrow) of the left forearm involves the whole dermal layer; (<b>b</b>) The inflammation (yellow arrows) is extended down to the deeper layer and, in particular, it involves the surgical grafts (green arrows); (<b>c</b>) Cicatricial fibrosis (red arrow) is also evident on the right side, where the adipose tissue appears inhomogeneous (yellow arrows) and where a cicatricial granuloma is present (white arrow); (<b>d</b>) The aspect described in <a href="#bioengineering-12-00179-f002" class="html-fig">Figure 2</a>c is similar in other areas of the right forearm, where other cicatricial granulomas are present (white arrow).</p>
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<p>Ultrasonography of the popliteal fossae at T0. (<b>a</b>) Wide section of cicatricial fibrosis (red arrow) of the left popliteal fossa with absence of clear anatomic layers (yellow arrow) and presence of a cicatricial granuloma (white arrow); (<b>b</b>) In another area of the left popliteal fossa the inhomogeneity of the tissues is evident (yellow arrow), and another cicatricial granuloma (white arrow) is present; (<b>c</b>) Cicatricial fibrosis (red arrow) is also evident on the right side, where the adipose tissue appears inhomogeneous (yellow arrows) and where multiple cicatricial granulomas (white arrow) are present in the deeper layer; (<b>d</b>) In another area of the right popliteal fossa, the superficial fibrosis (red arrows) appear less thick, and a partial restructuring of the deeper anatomical layers is noted (yellow arrow).</p>
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<p>Ultrasonography of the calves at T0. (<b>a</b>) Cicatricial fibrosis (red arrows) is evident on the left calf on the superficial layers. Phlogosis extends to the deeper layers (yellow arrow). A small fluid element (white arrow) is observed at the muscular level; (<b>b</b>) Cicatricial fibrosis (red arrow) is also evident on the right side, where the muscular structure (yellow arrow) appears preserved.</p>
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<p>Ultrasonography of the posterior thighs at T0. (<b>a</b>) On the left thigh, cicatricial fibrosis (red arrows) is evident on the superficial layers, and phlogosis extends to the deeper layers (yellow arrows); (<b>b</b>) On the right thigh, cicatricial fibrosis (red arrows) is present as on the left side, and the deeper layers present an inhomogeneous restructuring (yellow arrows).</p>
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<p>Ultrasonography of the forearms at T1. (<b>a</b>) A significant reduction of the cicatricial fibrosis (red arrow) is evident on the left forearm. A restructuring of all layers is also appreciable (yellow arrow). Moreover, some superficial vascular elements (blue arrow) are present; (<b>b</b>) The right forearm presents the same ameliorations described for the left forearm.</p>
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<p>Ultrasonography of the popliteal fossae at T1. (<b>a</b>) The left side presents a clear improvement in both the cicatricial fibrosis (red arrows) and the reorganization of the different structural layers (yellow arrow); (<b>b</b>) The right side presents the same effects of the treatment noted for the left side.</p>
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<p>Ultrasonography of the calves at T1. (<b>a</b>) The left side presents a clear improvement in both the cicatricial fibrosis (red arrow) and the reorganization of the different structural layers (yellow arrow). The muscular structure appears clearly defined, with a net improvement concerning the initial condition; (<b>b</b>) The right side presents the same treatment effects noted for the left side. On this side, the muscular structure was less compromised than that of the left side. The treatment acts on the connective tissue, softening the structure.</p>
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<p>Ultrasonography of the posterior thighs at T1. (<b>a</b>) On the left side, an improvement of the cicatricial fibrosis (red arrow) is clear. A restructuring of all the layers (yellow arrows) is also present; (<b>b</b>) The right side presents the same improvements as the left. The appearance of superficial vascular elements (blue arrows) is evident.</p>
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<p>Doppler ultrasound of the four areas analyzed. (<b>a</b>) Right forearm; (<b>b</b>) Left popliteal fossa; (<b>c</b>) Right calf; (<b>d</b>) Left posterior thigh. All the areas present a clear revascularization (blue arrows) extending to the deeper layers, particularly on the popliteal fossae and calves.</p>
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<p>Doppler ultrasound of the four areas analyzed. (<b>a</b>) Right forearm; (<b>b</b>) Left popliteal fossa; (<b>c</b>) Right calf; (<b>d</b>) Left posterior thigh. All the areas present a clear revascularization (blue arrows) extending to the deeper layers, particularly on the popliteal fossae and calves.</p>
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<p>Frontal and lateral postural evaluation.</p>
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<p>Postural evaluation. (<b>a</b>) At T0, the body shifted to the right and leaned forward. (<b>b</b>) At T2, the body was perfectly in line.</p>
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<p>Details of the scars at T2. (<b>a</b>) Forearms; (<b>b</b>) Left leg; (<b>c</b>) Right leg. In all the areas, fibrosis is reduced. Skin retraction and tissue depression are still present only in limited regions. The aesthetic improvement is correlated to functional motor improvement.</p>
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<p>Detail of hair regrowth on the leg.</p>
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23 pages, 6905 KiB  
Review
Bioresorbable Materials for Wound Management
by Hye-Min Lee and Hanjun Ryu
Biomimetics 2025, 10(2), 108; https://doi.org/10.3390/biomimetics10020108 - 12 Feb 2025
Abstract
Chronic wounds pose a significant healthcare challenge due to their risk of severe complications, necessitating effective management strategies. Bioresorbable materials have emerged as an innovative solution, offering advantages such as eliminating the need for secondary surgical removal, reducing infection risks, and enabling time-delayed [...] Read more.
Chronic wounds pose a significant healthcare challenge due to their risk of severe complications, necessitating effective management strategies. Bioresorbable materials have emerged as an innovative solution, offering advantages such as eliminating the need for secondary surgical removal, reducing infection risks, and enabling time-delayed drug delivery. This review examines recent advancements in bioresorbable wound healing materials, focusing on a systematic review of bioresorbable materials, systems incorporating electrical stimulation, and drug delivery technologies to accelerate tissue repair. The discussion encompasses the fundamental principles of bioresorbable materials, including their resorption mechanisms and key properties, alongside preclinical applications that demonstrate their practical potential. Critical challenges impeding widespread adoption are addressed, and prospects for integrating these cutting-edge systems into clinical practice are outlined. Together, these insights underscore the promise of bioresorbable materials in revolutionizing chronic wound care. Full article
(This article belongs to the Special Issue Advanced Biomaterials for Wound Healing Application)
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<p>Overview of this review. Fundamental mechanism of bioresorption and applications in wound healing (electrical stimulation and drug delivery).</p>
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<p>Bioresorbable materials. (<b>a</b>) Schematic illustration of the chemical reactions involved in the dissolution of bioresorbable metals (M: Mg, Zn, W, MO, Fe). (<b>b</b>) Schematic illustrations of the representative mechanisms involved in the in vivo resorption of bioresorbable polymers (PCL, PVA, PLA, PGA). (<b>c</b>) PCL, PVA, PLA, and PGA chemical structure in 2D. (<b>d</b>) Schematic illustration of the bioresorption process of silicon nanostructures (silicon nanowires, nanoribbons, nanomembranes) in bodily fluids.</p>
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<p>Chemical reactions involved in the dissolution of bioresorbable metals, polymers, and semiconductors [<a href="#B26-biomimetics-10-00108" class="html-bibr">26</a>]. (<b>a</b>) Series of images illustrating the dissolution of metal material patterns (<b>top</b>) and the corresponding reactions (<b>bottom</b>). (<b>b</b>) Series of images showing the dissolution of polymer material patterns (<b>top</b>) and the related reactions (<b>bottom</b>). (<b>c</b>) Series of images depicting the dissolution of semiconductor material patterns (<b>top</b>) and the associated reactions (<b>bottom</b>). Reprinted with permission from Zhang et al.; Copyright © 2023 American Chemical Society.</p>
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<p>Mo-based bioresorbable, wireless, battery-free electrical therapy systems (BESs) [<a href="#B86-biomimetics-10-00108" class="html-bibr">86</a>]. (<b>a</b>) Schematic illustration of Mo-based bioresorbable, wireless, battery-free electrical therapy systems (BESs). (<b>b</b>) CV of the Mo electrode in DPBS solution. (<b>c</b>) In vivo experimental results. (<b>d</b>) In vivo wireless current monitoring results between Mo electrodes. Reprinted with permission from Song et al.; Copyright © 2023 The American Association for the Advancement of Science.</p>
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<p>Natural-skin-derived organohydrogel (SGC@MA-Gel) triboelectric nanogenerator-based smart, battery-free, and wireless bioelectronic platform [<a href="#B92-biomimetics-10-00108" class="html-bibr">92</a>]. (<b>a</b>) Schematic illustration of the natural-skin-derived organohydrogel (SGC@MA-Gel) triboelectric nanogenerator-based smart, battery-free, and wireless bioelectronic platform. (<b>b</b>) In vivo experimental results. (<b>c</b>–<b>e</b>) Voltage output values under various experimental conditions. Reprinted with permission from Bai et al.; Copyright © 2023 Elsevier Ltd.</p>
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<p>Flexible TENG and triboelectric-responsive drug delivery hydrogel-based wearable triboelectric stimulator [<a href="#B100-biomimetics-10-00108" class="html-bibr">100</a>]. (<b>a</b>) Schematic illustration of the F-TENG and TR-DDH-based WTS. (<b>b</b>) Voltage, current, and charge output values under various frequency conditions. (<b>c</b>) In vivo experimental protocol. (<b>d</b>) In vivo experimental results. Reprinted with permission from Qin et al.; Copyright © 2024 Wiley-VCH GmbH.</p>
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<p>Drug delivery using PC-PPCN [<a href="#B106-biomimetics-10-00108" class="html-bibr">106</a>]. (<b>a</b>) Schematic illustration of drug delivery using PC-PPCN (<b>b</b>) In vivo experimental results. All data are presented as mean ± SD (<span class="html-italic">n</span> = 5; ns, not significant; * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01) Reprinted with permission from Wang et al.; Copyright © 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.</p>
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<p>Drug delivery using the hybrid biomaterial (Gel@fMLP/SiO<sub>2</sub>-FasL) [<a href="#B113-biomimetics-10-00108" class="html-bibr">113</a>]. (<b>a</b>) Schematic illustration of drug delivery using the hybrid biomaterial (Gel@fMLP/SiO<sub>2</sub>-FasL) (<b>b</b>) In vivo experimental results. Statistical analysis was performed by one-way ANOVA. ns, not significant; ** <span class="html-italic">p</span> &lt; 0.01. Reprinted with permission from Liu et al.; Copyright © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.</p>
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<p>Drug delivery using the bioactive hydrogel (OHA-CMC/CNP/EGF) [<a href="#B117-biomimetics-10-00108" class="html-bibr">117</a>]. (<b>a</b>) Schematic illustration of drug delivery using the bioactive hydrogel (OHA-CMC/CNP/EGF) (<b>b</b>) In vivo experimental results. The differences were regarded as statistically significant with * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and **** <span class="html-italic">p</span> &lt; 0.0001. Reprinted with permission from Hu et al.; Copyright © 2021 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd., Amsterdam, The Netherlands.</p>
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15 pages, 2861 KiB  
Article
Acute Biomechanical Effects of Cardiac Contractility Modulation in Living Myocardial Slices from End-Stage Heart Failure Patients
by Mark F. A. Bierhuizen, Jorik H. Amesz, Sanne J. J. Langmuur, Bobby Lam, Paul Knops, Kevin M. Veen, Olivier C. Manintveld, Jolanda Kluin, Natasja M. S. de Groot and Yannick J. H. J. Taverne
Bioengineering 2025, 12(2), 174; https://doi.org/10.3390/bioengineering12020174 - 12 Feb 2025
Abstract
Proof-of-concept to determine the direct biomechanical effects of cardiac contractility modulation (CCM) on living myocardial slices (LMS) from patients with end-stage heart failure (HF). Left ventricular LMS from patients with end-stage HF were produced and cultured in a biomimetic system with mechanical loading [...] Read more.
Proof-of-concept to determine the direct biomechanical effects of cardiac contractility modulation (CCM) on living myocardial slices (LMS) from patients with end-stage heart failure (HF). Left ventricular LMS from patients with end-stage HF were produced and cultured in a biomimetic system with mechanical loading and electrical stimulation. CCM stimulation (80 mA, 40 ms delay, 21 ms duration) enhanced maximum contractile force (CCM: 1229 µN (587–2658) vs. baseline: 1066 µN (529–2128), p = 0.05) and area under the contractile curve (CCM: 297 (151–562) vs. baseline: 243 (129–464), p = 0.05) but did not significantly impact contractile duration, time to peak, or time to relaxation. Increasing CCM stimulation delay, duration, and amplitude resulted in a higher fraction of LMS with a positive inotropic response. Furthermore, CCM attenuated the negative force-frequency relationship in HF-LMS. CCM stimulation enhanced contractile force in HF-LMS. The fraction of LMS exerting a positive inotropic response to CCM increased with increasing delay, duration, and amplitude settings, suggesting that personalizing stimulation parameters could optimize the beneficial effects of CCM. CCM is a novel device-based therapy that may improve contractile function, ejection fraction, functional outcomes, and quality of life in patients with heart failure. However, continuous efforts are needed to identify true responders to CCM therapy, understand the exact mechanisms, and optimize the contractile response to CCM stimulation. The present study revealed that CCM enhanced the contractile force of HF-LMS in a stimulation setting-dependent manner, reaching a larger fraction of the myocardium while increasing delay, duration, and amplitude. This understanding may contribute to the individualization of CCM stimulation settings. Full article
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<p>(<b>A</b>) illustrates the LMS cultivation set-up. (<b>B</b>) shows definitions of excitatory and CCM pulse parameters and contractile measurements. AUC: area under the curve; CD: contraction duration; CD<sub>50</sub>: peak width at 50% of the maximum amplitude; F<sub>max</sub>: maximum contraction force; TTP: time to peak; TTR: time to relaxation; +dF/dt: steepest positive slope; −dF/dt: steepest negative slope.</p>
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<p>CCM stimulation enhanced F<sub>max</sub> gradually for up to 3 min and then stabilized in LMS with positive inotropy (n = 42) from heart failure patients (n = 7). Typical contractile tracings were provided. Data are expressed as median and IQR, with added individual data points.</p>
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<p>Biomechanical effects of increasing CCM pulse delay (10–200 ms) in LMS (CCM amplitude 80 mA, 21 ms duration). Increasing delay enhanced F<sub>max</sub>, AUC, +dF/dt, and −dF/dt, but did not alter TTP or TTR. Data are expressed as median and IQR, with added individual data points. Clustered Wilcoxon signed rank tests were used to compare contractile parameters for delay 10 ms (n = 60), 20 ms (n = 60), 30 ms (n = 60), 40 ms (n = 60), 50 ms (n = 55), 70 ms (n = 49), 100 ms (n = 55), 150 ms (n = 47), and 200 ms (n = 53). * <span class="html-italic">p</span> ≤ 0.05.</p>
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<p>(<b>A</b>): Contractile tracings of HF-LMS with a negative, neutral, and positive inotropic response during CCM stimulation. (<b>B</b>–<b>D</b>)<span class="html-italic">:</span> Inotropic response of HF-LMS to varying CCM stimulation parameters. A higher fraction of LMS showed a positive inotropic response with increasing CCM pulse delay, amplitude, and duration. Fractions were calculated for pulse delay 10 (n = 60), 20 (n = 60), 30 (n = 60), 40 (n = 60), 50 (n = 55), 70 (n = 49), 100 (n = 55), 150 (n = 47), and 200 ms (n = 53); pulse duration 11 (n = 48), 21 (n = 64), 31 (n = 59), and 41 ms (n = 58); pulse amplitude 1× (n = 54), 2× (n = 54), 3× (n = 56), and 4× threshold (n = 56).</p>
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<p>(<b>A</b>): Partial reversal of the negative force-frequency relationship (FFR) with CCM stimulation. The number of included LMS at higher frequencies decreased from 57 to 24 due to exclusion of LMS when contractions did not capture all electrical stimuli. (<b>B</b>): The FFR of 24 LMS with capture of all pacing frequencies (30 to 180 bpm). (<b>C</b>,<b>D</b>) illustrate the F<sub>max</sub> of 24 LMS before and during CCM stimulation at 30 to 180 bpm, respectively.</p>
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14 pages, 1163 KiB  
Article
Modulation of Primary Afferent Nerve Fiber (Ia) Reciprocal Inhibition Under Voluntary and Electrically Stimulated Muscle Conditions: Within-Subject Study Design
by Sami S. AlAbdulwahab, Seraj H. Altwerqi, Adnan A. Mubaraki and Maha F. Algabbani
J. Clin. Med. 2025, 14(4), 1178; https://doi.org/10.3390/jcm14041178 - 11 Feb 2025
Abstract
Background: Reciprocal inhibition (RI) is a spinal reflex that controls posture and movement. The modulation of spinal RI represented by the H-reflex has been studied, before and after voluntary contraction and electrical nerve stimulation but not during voluntary, electrically induced muscle contraction or [...] Read more.
Background: Reciprocal inhibition (RI) is a spinal reflex that controls posture and movement. The modulation of spinal RI represented by the H-reflex has been studied, before and after voluntary contraction and electrical nerve stimulation but not during voluntary, electrically induced muscle contraction or a combination of voluntary and electrically induced muscle contractions. This study investigates the effects of the ongoing voluntary isometric contraction, the electrically induced isometric contraction, and the combination of voluntary with electrically induced isometric contraction of the Tibialis Anterior (TA) muscle on spinal RI represented by Soleus H-reflex. Methods: Eighteen healthy adults participated. Soleus H-reflex and M-response were measured during four different conditions as follows: (1) at rest, (2) electrically induced isometric contraction of the TA, (3) voluntary isometric contraction of the TA with a 1 kg force, and (4) combined voluntary and electrically induced isometric contraction of the TA with a 1 kg force. Results: The ANOVA clearly demonstrated significant differences in Soleus H-reflex amplitude across the four recording conditions (F3,16, 17.28, p < 0.001). The amplitude at rest was significantly higher than during electrically induced isometric contraction, voluntary isometric contraction, and the combined contraction conditions (p < 0.05). Furthermore, the amplitude recorded during the electrically induced isometric contraction condition significantly surpassed that of voluntary isometric contraction and the combined contraction conditions (p < 0.05). Moreover, there was no significant difference between Soleus H-reflex amplitude recorded during voluntary isometric contraction and the combined voluntary isometric contraction and electrically induced isometric contraction (p < 0.87). The combined voluntary isometric contraction and electrically induced isometric contraction condition had a higher inhibitory effect on the Soleus H-reflex with no significant differences from voluntary isometric contraction. Moreover, both were significantly better than electrically induced isometric contraction (p = 0.05). In terms of Soleus H-reflex latency, there was no significant difference among all four conditions (p > 0.05), meaning Soleus H-reflex latency was not influenced by the conditions. Conclusions: RI can be best modulated by combining voluntary with electrically induced isometric muscle contractions. Full article
(This article belongs to the Section Clinical Neurology)
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<p>The EMG electrode placement. A: pin electrode position; B: ground electrode; C: active electrode; D: reference electrodes.</p>
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<p>Soleus M-response and H-reflex amplitudes (mV) and latencies (ms) during the four different conditions. These conditions exhibited an inhibitory effect, reducing the H-reflex amplitudes.</p>
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<p>Ways in which RI can influence the H-reflex amplitude in an antagonist muscle.</p>
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29 pages, 4362 KiB  
Review
Sustainable Geothermal Energy: A Review of Challenges and Opportunities in Deep Wells and Shallow Heat Pumps for Transitioning Professionals
by Tawfik Elshehabi and Mohammad Alfehaid
Energies 2025, 18(4), 811; https://doi.org/10.3390/en18040811 - 9 Feb 2025
Abstract
Geothermal energy has emerged as a cornerstone in renewable energy, delivering reliable, low-emission baseload electricity and heating solutions. This review bridges the current knowledge gap by addressing challenges and opportunities for engineers and scientists, especially those transitioning from other professions. It examines deep [...] Read more.
Geothermal energy has emerged as a cornerstone in renewable energy, delivering reliable, low-emission baseload electricity and heating solutions. This review bridges the current knowledge gap by addressing challenges and opportunities for engineers and scientists, especially those transitioning from other professions. It examines deep and shallow geothermal systems and explores the advanced technologies and skills required across various climates and environments. Transferable expertise in drilling, completion, subsurface evaluation, and hydrological assessment is required for geothermal development but must be adapted to meet the demands of high-temperature, high-pressure environments; abrasive rocks; and complex downhole conditions. Emerging technologies like Enhanced Geothermal Systems (EGSs) and closed-loop systems enable sustainable energy extraction from impermeable and dry formations. Shallow systems utilize near-surface thermal gradients, hydrology, and soil conditions for efficient heat pump operations. Sustainable practices, including reinjection, machine learning-driven fracture modeling, and the use of corrosion-resistant alloys, enhance well integrity and long-term performance. Case studies like Utah FORGE and the Geysers in California, US, demonstrate hydraulic stimulation, machine learning, and reservoir management, while Cornell University has advanced integrated hybrid geothermal systems. Government incentives, such as tax credits under the Inflation Reduction Act, and academic initiatives, such as adopting geothermal energy at Cornell and Colorado Mesa Universities, are accelerating geothermal integration. These advancements, combined with transferable expertise, position geothermal energy as a major contributor to the global transition to renewable energy. Full article
(This article belongs to the Special Issue The Future of Renewable Energy: 2nd Edition)
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<p>Trends in geothermal publications (2004–2024), illustrating growing research focus on emerging technologies and opportunities (<b>left</b>). The right panel shows the distribution of references by category and publication type, including drilling, design, materials, geomechanics, shallow systems, case studies, and emerging techniques in geothermal research (<b>right</b>).</p>
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<p>Coaxial and U-shaped geothermal well designs showing the flow of fluid down the annular space or injector well, heat absorption downhole, and the return of fluid to the surface for efficient geothermal energy extraction [<a href="#B40-energies-18-00811" class="html-bibr">40</a>].</p>
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<p>Geothermal energy extraction through hydrothermal and hot-rock systems (EGSs), illustrating fluid circulation in permeable sediments and heat recovery using hydraulic fracture systems within high-heat-producing granite [<a href="#B69-energies-18-00811" class="html-bibr">69</a>].</p>
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<p>Schematics for a rotary drilling rig, including mud circulation for cooling the drill bit (adapted from [<a href="#B83-energies-18-00811" class="html-bibr">83</a>]). Schematics on the right depict three geothermal heat pump configurations: Ground-Coupled Heat Pump (GCHP), Groundwater Heat Pump (GWHP), and Surface-Water Heat Pump (SWHP) systems (adapted from [<a href="#B80-energies-18-00811" class="html-bibr">80</a>,<a href="#B81-energies-18-00811" class="html-bibr">81</a>] with adjustments to improve labeling and organization).</p>
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<p>Soil temperature variation with respect to depth for wet, average, and light dry soils. Temperature fluctuations decrease with increasing depth [<a href="#B92-energies-18-00811" class="html-bibr">92</a>].</p>
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<p>Temperature map at a depth of 7.5 km across the United States, showing geothermal gradients with higher temperatures (red to purple) in the western region. Blue stars indicate case study sites: The Geysers in California, Utah FORGE, and Cornell University. Adapted by highlighting the case study sites from [<a href="#B102-energies-18-00811" class="html-bibr">102</a>].</p>
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<p>Wellbore schematics for Prati State 31 and Prati 32 at The Geysers, highlighting casing designs, liner configurations, and high-temperature zones critical for geothermal reservoir management [<a href="#B107-energies-18-00811" class="html-bibr">107</a>].</p>
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<p>Geothermal systems at Cornell University. <b>Left</b>, a schematic of Cornell’s Earth Source Heat, featuring planned production and injection wells [<a href="#B115-energies-18-00811" class="html-bibr">115</a>]. <b>Right</b>, a schematic of the Lake Source Cooling System [<a href="#B114-energies-18-00811" class="html-bibr">114</a>].</p>
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15 pages, 2352 KiB  
Communication
Effects of Gait Rehabilitation Robot Combined with Electrical Stimulation on Spinal Cord Injury Patients’ Blood Pressure
by Takahiro Sato, Ryota Kimura, Yuji Kasukawa, Daisuke Kudo, Kazutoshi Hatakeyama, Motoyuki Watanabe, Yusuke Takahashi, Kazuki Okura, Tomohiro Suda, Daido Miyamoto, Takehiro Iwami and Naohisa Miyakoshi
Sensors 2025, 25(3), 984; https://doi.org/10.3390/s25030984 - 6 Feb 2025
Abstract
Background: Orthostatic hypotension can occur during acute spinal cord injury (SCI) and subsequently persist. We investigated whether a gait rehabilitation robot combined with functional electrical stimulation (FES) stabilizes hemodynamics during orthostatic stress in SCI. Methods: Six intermediate-phase SCI patients (five males and one [...] Read more.
Background: Orthostatic hypotension can occur during acute spinal cord injury (SCI) and subsequently persist. We investigated whether a gait rehabilitation robot combined with functional electrical stimulation (FES) stabilizes hemodynamics during orthostatic stress in SCI. Methods: Six intermediate-phase SCI patients (five males and one female; mean age: 49.5 years; four with quadriplegia and two with paraplegia) participated. The participants underwent robotic training (RT), with a gait rehabilitation robot combined with FES, and tilt table training (TT). Hemodynamics were monitored using a laser Doppler flowmeter for the earlobe blood flow (EBF) and non-invasive blood pressure measurements. The EBF over time and the resting and exercise blood pressures were compared between each session. Adverse events were also evaluated. Results: The EBF change decreased in TT but increased in RT at the 0.5-min slope (p = 0.03). Similarly, the pulse rate change increased in TT but decreased in RT at the 1-min slope (p = 0.03). Systolic and mean blood pressures were slightly higher in RT than in TT but not significantly (p = 0.35; 0.40). No adverse events occurred in RT, but two TT sessions were incomplete due to dizziness. Conclusions: RT with FES can reduce symptoms during orthostatic stress in intermediate-phase SCI. Future studies require a larger number of cases to generalize this study. Full article
(This article belongs to the Section Biomedical Sensors)
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<p>A gait rehabilitation robot combined with functional electrical stimulation: Akita Trainer.</p>
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<p>The positions of the functional electrical stimulation pads. The pads were placed on the quadriceps and hamstrings on both sides (silver pads).</p>
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<p>Wireless laser Doppler blood flow meter: Pocket LDF.</p>
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<p>Graphs of the EBF ratio and systolic blood pressure after training. Black and gray lines indicate the EBF ratios in robot training and tilt table training, respectively. Black and gray dots indicate the systolic blood pressure during robot training and tilt table training, respectively.</p>
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<p>Graphs of the EBF ratio and systolic blood pressure after training. Black and gray lines indicate the EBF ratios in robot training and tilt table training, respectively. Black and gray dots indicate the systolic blood pressure during robot training and tilt table training, respectively.</p>
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<p>Graphs of the EBF ratio and systolic blood pressure after training. Black and gray lines indicate the EBF ratios in robot training and tilt table training, respectively. Black and gray dots indicate the systolic blood pressure during robot training and tilt table training, respectively.</p>
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<p>Box and whisker plot showing changes in the slope of the regression line of the EBF at 30 s and every 1 min. White indicates robot training and dark gray indicates tilt table. *: <span class="html-italic">p</span> &lt; 0.05 vs. TT exercise group at 0.5 min using the Wilcoxon rank-sum test.</p>
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<p>Box and whisker plot showing changes in the slope of the regression line of pulse rate at 30 s and every 1 min. White indicates robot training and dark gray indicates tilt table. *: <span class="html-italic">p</span> &lt; 0.05 vs. TT exercise group at 0.5 min using the Wilcoxon rank-sum test.</p>
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11 pages, 759 KiB  
Article
Combined Neuromuscular Electrical Stimulation and Elastic Taping Improves Ankle Range of Motion Equivalent to Static Stretching in Untrained Subjects
by Riyaka Ito, Tatsuya Igawa, Ryunosuke Urata, Shomaru Ito, Kosuke Suzuki, Hiroto Takahashi, Mika Toda, Mio Fujita and Akira Kubo
J. Funct. Morphol. Kinesiol. 2025, 10(1), 58; https://doi.org/10.3390/jfmk10010058 - 6 Feb 2025
Abstract
Background/Objective: Maintaining sufficient ankle joint range of motion (ROM) contributes to efficient movement in sports and daily activities. Static stretching (SS), while effective, demands significant time, highlighting the need for alternative, time-efficient approaches to improve ROM. Therefore, this study aimed to evaluate [...] Read more.
Background/Objective: Maintaining sufficient ankle joint range of motion (ROM) contributes to efficient movement in sports and daily activities. Static stretching (SS), while effective, demands significant time, highlighting the need for alternative, time-efficient approaches to improve ROM. Therefore, this study aimed to evaluate the effectiveness of combined intervention (CI) using neuromuscular electrical stimulation (NMES) and elastic tape versus SS. Methods: This randomized crossover trial was conducted in healthy university students. They underwent both interventions with a 1-week washout period. The CI entailed the application of elastic tape to the plantar surface of the foot coupled with NMES targeting the posterior lower leg muscles for 1 min. SS was administered for 5 min using a tilt table. Outcome measures included the dorsiflexion angle (DFA), finger-floor distance (FFD), straight leg raise (SLR) angle, plantar flexor strength (PFS), and knee flexor strength (KFS), assessed pre- and post-intervention. DFA was analyzed using equivalence testing with a predefined margin. Results: Both interventions yielded significant improvements in DFA, FFD, and SLR. The combination of NMES and elastic tape demonstrated equivalence to 5 min of SS in enhancing DFA. Neither intervention resulted in a significant reduction in PFS or KFS. Conclusions: The CI of NMES and elastic tape effectively and safely improves flexibility in a short time. Its time efficiency makes it a promising alternative to SS, especially for brief warm-ups or limited rehabilitation time. Further research should explore its long-term effects and broader applicability. Full article
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<p>Flowchart of the crossover process. NMES, neuromuscular electrical stimulation.</p>
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<p>Difference in DFA from baseline to each follow-up between CI and SS. M = (DFA immediately after intervention) − (DFA at baseline). M<sub>CI</sub>, combined intervention; M<sub>SS</sub>, static stretching; CI, confidence interval.</p>
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17 pages, 4074 KiB  
Article
A Platform Integrating Biophysical and Biochemical Stimuli to Enhance Differentiation and Maturation of Cardiomyocyte Subtypes Derived from Human Induced Pluripotent Stem Cells
by Zhonggang Feng, Kota Sawada, Iori Ando, Riku Yoshinari, Daisuke Sato and Tadashi Kosawada
J. Cardiovasc. Dev. Dis. 2025, 12(2), 56; https://doi.org/10.3390/jcdd12020056 - 4 Feb 2025
Abstract
To enhance the differentiation and maturation of cardiomyocytes derived from human induced pluripotent stem cells, we developed a bioreactor system that simultaneously imposes biophysical and biochemical stimuli on these committed cardiomyocytes. The cells were cultured within biohydrogels composed of the extracellular matrix extracted [...] Read more.
To enhance the differentiation and maturation of cardiomyocytes derived from human induced pluripotent stem cells, we developed a bioreactor system that simultaneously imposes biophysical and biochemical stimuli on these committed cardiomyocytes. The cells were cultured within biohydrogels composed of the extracellular matrix extracted from goat ventricles and purchased rat-origin collagen, which were housed in the elastic PDMS culture chambers of the bioreactor. Elastic and flexible electrodes composed of PEDOT/PSS, latex, and graphene flakes were embedded in the hydrogels and chamber walls, allowing cyclic stretch and electrical pulses to be simultaneously and coordinately applied to the cultured cells. Furthermore, a dynamic analysis method employing the transverse forced oscillation theory of a cantilever was used to analyze and discriminate the subtype-specific beating behavior of the cardiomyocytes. It was found that myosin light chain 2v (MLC2v), a ventricular cell marker, was primarily upregulated in cells aggregated on the (+) electrode side, while cardiomyocytes with faint MLC2v but strong cardiac troponin T (cTNT) expression aggregated at the ground electrode (GND) side. mRNA analysis using rtPCR and the gel beating dynamics further suggested a subtype deviation on the different electrode sides. This study demonstrated the potential of our bioreactor system in enhancing cardiac differentiation and maturation, and it showed an intriguing phenomenon of cardiomyocyte subtype aggregation on different electrodes, which may be developed into a new method to enhance the maturation and separation of cardiomyocyte subtypes. Full article
(This article belongs to the Section Cardiac Development and Regeneration)
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<p>Integrated bioreactor system for 3D culture of hiPS-CMs. (<b>a</b>) Photograph of the complete system, designed for 3D culture of hiPS-CMs embedded in vECM-collagen hydrogel within the integrated bioreactor. The bioreactor applies mechanical and electrical stimulation to the hydrogels inside its culture chambers, which are housed in a commercially available 5% CO<sub>2</sub> incubator. (<b>b</b>) Schematic diagram of the system illustrating its operational mechanism, connections between components, and the coordination of mechanical and electrical stimulation via trigger signaling.</p>
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<p>Details of the culture chambers and the electrodes within the bioreactor. (<b>a</b>) Photograph showing two culture chambers installed into the bioreactor system. (<b>b</b>) Demonstration of the elastic stretchability of the conductive electrode material (PEDOT/PSS-latex-rGO), developed in-house. (<b>c</b>) Configuration of the electrodes embedded within the PDMS culture chambers, highlighting their integration for effective electrical stimulation.</p>
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<p>Photograph of device for the beating force measurement (<b>a</b>) and its schematic drawing (<b>b</b>). Arrows in (<b>b</b>) indicate stage-moving directions.</p>
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<p>Dynamic evaluation of the beating force. (<b>a</b>) Recorded displacement at the free end of the cantilever probe during hiPS-CM beating. (<b>b</b>) Dynamic waveform of the beating force derived using the transverse forced oscillation theory for a cantilever. The evaluation parameters are annotated on the force waveform in (<b>b</b>).</p>
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<p>Mechanical compatibility between the culture chamber and its embedded electrodes. (<b>a</b>) Tensile stress–strain relationship of the PDMS material used for the culture chambers. (<b>b</b>) Stress–strain relationship of the elastic electrode material. (<b>c</b>) Measurement of surface stretch strain at three regions (GND, middle, and (+) side) on the cultured gel. Insets in (<b>a</b>,<b>b</b>) are the stress–strain relationships within 0–0.1 strain range.</p>
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<p>(<b>a</b>) Waveforms of the mechanical and electrical stimuli, with the parameters defining the stimulations. (<b>b</b>) Measured electrical pulse at three regions relative to the electrodes in the cultured gel.</p>
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<p>Differentiation status after first monolayer differentiation stage of 15 days. (<b>a</b>) Video clip of hiPS-CMs beating and (<b>b</b>) mRNA relative expressions with respect to the internal reference GAPDH at the end of this stage (data plotted by means and SD, n = 5; asterisk indicates <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Dynamic evaluation of beating force under mechanical and electrical stimulation at low (1.0 Hz) and high (5.0 Hz) frequencies. (<b>a</b>) Maximum beating force <span class="html-italic">B<sub>m</sub></span>, (<b>b</b>) contraction velocity <span class="html-italic">F<sub>C</sub></span>, relaxation velocity <span class="html-italic">F<sub>r</sub></span>, and force-time integral <span class="html-italic">FI</span>, and (<b>c</b>) corresponding normalized parameters <span class="html-italic">F’<sub>C</sub></span>, <span class="html-italic">F’<sub>r</sub></span>, and <span class="html-italic">FI’</span>. (data plotted as mean ± SD, two experiments were conducted and n = 3~5 beating force waveforms were analyzed for each experiment; asterisk indicates <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Observation of <span class="html-italic">cTnT</span>, DAPI, and <span class="html-italic">MLC2v</span> expression in cells cultured at different portions of gels relative to the electrodes under stimulation at frequencies of 1.0 Hz, nine panels in (<b>a</b>) and of 5.0 Hz, nine panels in (<b>b</b>). It should be kept in mind that, since these images were taken within the 3D hydrogels, the resolution was quite compromised—particularly when the target markers were less expressed, as seen in (<b>a</b>).</p>
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<p>Relative mRNA expression of at GND and (+) sites under 5.0 Hz stimulation. Expressions were analyzed using the ΔΔCT method. The control group consisted of 3D cultures in vECM-collagen hydrogels without any physical stimulation. (n = 2, with two measurements and their average shown for each result).</p>
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18 pages, 611 KiB  
Article
Blockchain-Enhanced Demand-Side Management for Improved Energy Efficiency and Decentralized Control
by Ameni Boumaiza
Sustainability 2025, 17(3), 1228; https://doi.org/10.3390/su17031228 - 3 Feb 2025
Abstract
Blockchain technology introduces significant advancements in demand-side management (DSM) by enabling decentralized, transparent, and secure data handling within energy systems. This study explores a blockchain-based approach aimed at improving electricity efficiency through enhanced DSM strategies. We present a comprehensive framework that integrates blockchain [...] Read more.
Blockchain technology introduces significant advancements in demand-side management (DSM) by enabling decentralized, transparent, and secure data handling within energy systems. This study explores a blockchain-based approach aimed at improving electricity efficiency through enhanced DSM strategies. We present a comprehensive framework that integrates blockchain technology with real-time data analytics to optimize energy consumption, stimulate consumer participation, and support efficient energy utilization. The experimental analysis demonstrates that blockchain integration significantly strengthens DSM operations by reducing operational costs, increasing participation in demand response programs, and enhancing grid stability. The findings highlight the effectiveness and potential of the proposed approach as a forward-looking solution for energy management systems. Full article
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<p>Analysis of DSM System Architecture. The figure illustrates energy consumption, blockchain transaction records, incentive rates, and DSM control signals over a 24-h period, highlighting the interaction between data, blockchain, and application layers.</p>
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<p>Experimental Analysis: (<b>a</b>) Energy Consumption Over Time, (<b>b</b>) Incentivization Reward Accumulation Over Peak Hours, (<b>c</b>) Adjusted Supply and Demand Over Time.</p>
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<p>Comparative Analysis of Traditional DSM vs Blockchain-based DSM across Transaction Costs, Latency, User Participation Rates, and Energy Savings.</p>
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<p>Performance Improvements in DSM Metrics. The figure illustrates a 25% reduction in electricity costs for consumers, a 30% increase in demand response participation rate, and a 15% improvement in grid stability, demonstrating the effectiveness of the proposed DSM model.</p>
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25 pages, 3015 KiB  
Review
Magnetic Polymeric Conduits in Biomedical Applications
by Sayan Ganguly and Shlomo Margel
Micromachines 2025, 16(2), 174; https://doi.org/10.3390/mi16020174 - 31 Jan 2025
Abstract
Magnetic polymeric conduits are developing as revolutionary materials in regenerative medicine, providing exceptional benefits in directing tissue healing, improving targeted medication administration, and facilitating remote control via external magnetic fields. The present article offers a thorough examination of current progress in the design, [...] Read more.
Magnetic polymeric conduits are developing as revolutionary materials in regenerative medicine, providing exceptional benefits in directing tissue healing, improving targeted medication administration, and facilitating remote control via external magnetic fields. The present article offers a thorough examination of current progress in the design, construction, and functionalization of these hybrid systems. The integration of magnetic nanoparticles into polymeric matrices confers distinctive features, including regulated alignment, improved cellular motility, and targeted medicinal delivery, while preserving structural integrity. Moreover, the incorporation of multifunctional attributes, such as electrical conductivity for cerebral stimulation and optical characteristics for real-time imaging, expands their range of applications. Essential studies indicate that the dimensions, morphology, surface chemistry, and composition of magnetic nanoparticles significantly affect their biocompatibility, degrading characteristics, and overall efficacy. Notwithstanding considerable advancements, issues concerning long-term biocompatibility, biodegradability, and scalability persist, in addition to the must for uniform regulatory frameworks to facilitate clinical translation. Progress in additive manufacturing and nanotechnology is overcoming these obstacles, facilitating the creation of dynamic and adaptive conduit structures designed for particular biomedical requirements. Magnetic polymeric conduits, by integrating usefulness and safety, are set to transform regenerative therapies, presenting a new avenue for customized medicine and advanced healthcare solutions. Full article
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<p>(<b>A</b>) Oleic acid-coated SPIONs are mixed with 8% PLLA in chloroform, followed by electrospinning onto a rotating mandrel to create aligned fibers. (<b>B</b>) Fiber mats are cut into 3 mm × 5 mm segments and rolled into small conduits. (<b>C</b>) Conduits and hydrogel are injected into a chamber. (<b>D</b>) A magnetic field is applied to align fibers within the hydrogel until solidified. (<b>E</b>) Fibers remain aligned after the field is removed, supporting neurite guidance from the dorsal root ganglion. (<b>F</b>–<b>I</b>) SEM images of a 6% SPION fiber conduit. Reproduced with permission from ref. [<a href="#B82-micromachines-16-00174" class="html-bibr">82</a>]. © American Chemical Society.</p>
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<p>Schematic representation of the fabrication of an NGF@MPs-GS nerve conduit. Reproduced with permission of ref. [<a href="#B101-micromachines-16-00174" class="html-bibr">101</a>]. © American Chemical Society.</p>
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<p>(<b>A</b>) A typical experiment chip (left panel) and microfluidic channels with zigzag-shaped permalloy (Ni80Fe20) microstripes (right panel). The serpentine’s empty half is light gray, while the left panel’s liquid-filled channel is light blue. (<b>B</b>) Bright-field (BF) image of MNB-polymer 8 aggregates trapped by DWs at several corners of one of the zigzag-shaped magnetic conduits at 45 °C and FITC-filtered image showing the aggregates’ fluorescence due to doxorubicin molecules in the magnetic nanobeads. In the BF and FITC filtered image, the insets zoom in on a trapped polymeric aggregate. (<b>C</b>) Fluorescence intensity vs. time curves of MNB-polymer 8 at various flow rates (left panel); MNB-polymer 8, 9, and 10 at 1.0 μL/min flow rate (central panel); and cumulative DOXO release profile from MNBs coated with polymers 8, 9, and 10 without flow rate (right panel). Reproduced with permission of ref. [<a href="#B103-micromachines-16-00174" class="html-bibr">103</a>]. © American Chemical Society.</p>
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<p>Types of hyperthermia and action in the human body.</p>
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<p>Gradient fields enabling arbitrary magnetic hyperthermia therapy localization in vivo using magnetic particle imaging. Reproduced with permission from ref. [<a href="#B104-micromachines-16-00174" class="html-bibr">104</a>]. © American Chemical Society.</p>
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<p>Confocal images of Phalloidin/DAPI staining of PC12 cells in plain collagen scaffolds (<b>A</b>), GMNP-incorporated scaffolds without magnetic field treatment (<b>B</b>), “magnetic particle string” scaffolds (<b>C</b>), CMP-functionalized scaffolds (<b>D</b>), and “magnetic anchor” scaffolds (<b>E</b>). Image (<b>F</b>) shows how differentiated PC12 cells were measured; yellow lines show axonal length, and red lines demonstrate alignment. The angle of alignment (θ) is determined from the horizontal plane (0°). Reproduced with permission from ref. [<a href="#B115-micromachines-16-00174" class="html-bibr">115</a>]. © MDPI.</p>
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<p>Diagram illustrating the characteristics of short-peptide supramolecular magnetic hydrogels. Reproduced with permission from ref. [<a href="#B116-micromachines-16-00174" class="html-bibr">116</a>]. © American Chemical Society.</p>
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