Effect of electrical stimulation on biological cells by capacitive coupling – an efficient numerical study considering model uncertainties

2020 ◽  
Author(s):  
Julius Zimmermann ◽  
RIchard Altenkirch ◽  
Ursula van Rienen
Keyword(s):  
Electrical Stimulation ◽  
Cell Membrane ◽  
Electric Fields ◽  
Biological Samples ◽  
Numerical Study ◽  
Cell Activity ◽  
Cellular Level ◽  
Capacitive Coupling ◽  
Fe Method

Electrical stimulation of biological samples such as tissues and cell cultures attracts growing attention due to its capability of enhancing cell activity, proliferation and differentiation. <br>Eventually, profound knowledge of the underlying mechanisms paves the way for innovative therapeutic devices. <br>Capacitive coupling is one option of delivering electric fields to biological samples and has advantages with regard to biocompatibility.<br>However, the mechanism of interaction is not well understood.<br>Experimental findings could be related to voltage-gated channels, which are triggered by changes of the transmembrane potential (TMP).<br>Numerical simulations by the Finite Element method (FEM) provide a possibility to estimate the TMP.<br>For realistic simulations of <i>in vitro</i> electric stimulation experiments, a bridge from the mesoscopic level down to the cellular level has to be found.<br>A special challenge poses the ratio between the cell membrane (a few <i>nm</i>) and the general setup (some <i>cm</i>).<br>Hence, a full discretization of the cell membrane becomes prohibitively expensive for 3D simulations.<br>We suggest using an approximate FE method that makes 3D multi-scale simulations possible.<br>Starting from an established 2D model, the chosen method is characterized and applied to realistic <i>in vitro</i> situations.<br>A to date not investigated parameter dependency is included and tackled by means of Uncertainty Quantification (UQ) techniques.<br>It reveals a strong, frequency-dependent influence of uncertain parameters on the modeling result.<br><br>

Effect of electrical stimulation on biological cells by capacitive coupling – an efficient numerical study considering model uncertainties

2020 ◽  
Author(s):  
Julius Zimmermann ◽  
RIchard Altenkirch ◽  
Ursula van Rienen
Keyword(s):  
Electrical Stimulation ◽  
Cell Membrane ◽  
Electric Fields ◽  
Biological Samples ◽  
Numerical Study ◽  
Cell Activity ◽  
Cellular Level ◽  
Capacitive Coupling ◽  
Fe Method

Electrical stimulation of biological samples such as tissues and cell cultures attracts growing attention due to its capability of enhancing cell activity, proliferation and differentiation. <br>Eventually, profound knowledge of the underlying mechanisms paves the way for innovative therapeutic devices. <br>Capacitive coupling is one option of delivering electric fields to biological samples and has advantages with regard to biocompatibility.<br>However, the mechanism of interaction is not well understood.<br>Experimental findings could be related to voltage-gated channels, which are triggered by changes of the transmembrane potential (TMP).<br>Numerical simulations by the Finite Element method (FEM) provide a possibility to estimate the TMP.<br>For realistic simulations of <i>in vitro</i> electric stimulation experiments, a bridge from the mesoscopic level down to the cellular level has to be found.<br>A special challenge poses the ratio between the cell membrane (a few <i>nm</i>) and the general setup (some <i>cm</i>).<br>Hence, a full discretization of the cell membrane becomes prohibitively expensive for 3D simulations.<br>We suggest using an approximate FE method that makes 3D multi-scale simulations possible.<br>Starting from an established 2D model, the chosen method is characterized and applied to realistic <i>in vitro</i> situations.<br>A to date not investigated parameter dependency is included and tackled by means of Uncertainty Quantification (UQ) techniques.<br>It reveals a strong, frequency-dependent influence of uncertain parameters on the modeling result.<br><br>

scholarly journals Establishment of a New Device for Electrical Stimulation of Non-Degenerative Cartilage Cells In Vitro

2021 ◽  
Vol 22 (1) ◽  
pp. 394
Author(s):  
Simone Krueger ◽  
Alexander Riess ◽  
Anika Jonitz-Heincke ◽  
Alina Weizel ◽  
Anika Seyfarth ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Electric Fields ◽  
Cartilage Tissue ◽  
Type I ◽  
Dependent Manner ◽  
New Device ◽  
Alternating Electric Fields ◽  
Cartilage Cells ◽  
Stimulation Of

In cell-based therapies for cartilage lesions, the main problem is still the formation of fibrous cartilage, caused by underlying de-differentiation processes ex vivo. Biophysical stimulation is a promising approach to optimize cell-based procedures and to adapt them more closely to physiological conditions. The occurrence of mechano-electrical transduction phenomena within cartilage tissue is physiological and based on streaming and diffusion potentials. The application of exogenous electric fields can be used to mimic endogenous fields and, thus, support the differentiation of chondrocytes in vitro. For this purpose, we have developed a new device for electrical stimulation of chondrocytes, which operates on the basis of capacitive coupling of alternating electric fields. The reusable and sterilizable stimulation device allows the simultaneous use of 12 cavities with independently applicable fields using only one main supply. The first parameter settings for the stimulation of human non-degenerative chondrocytes, seeded on collagen type I elastin-based scaffolds, were derived from numerical electric field simulations. Our first results suggest that applied alternating electric fields induce chondrogenic re-differentiation at the gene and especially at the protein level of human de-differentiated chondrocytes in a frequency-dependent manner. In future studies, further parameter optimizations will be performed to improve the differentiation capacity of human cartilage cells.

scholarly journals Modulation of VEGFR-2–mediated endothelial-cell activity by VEGF-C/VEGFR-3

Blood ◽  
2003 ◽  
Vol 101 (4) ◽  
pp. 1367-1374 ◽  
Author(s):  
Kazuyoshi Matsumura ◽  
Masanori Hirashima ◽  
Minetaro Ogawa ◽  
Hajime Kubo ◽  
Hiroshi Hisatsune ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Activity ◽  
Embryonic Stem ◽  
Cellular Level ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Vascular Integrity ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR-3), a receptor for VEGF-C, was shown to be essential for angiogenesis as well as for lymphangiogenesis. Targeted disruption of theVEGFR-3 gene in mice and our previous study using an antagonistic monoclonal antibody (MoAb) for VEGFR-3 suggested that VEGF-C/VEGFR-3 signals might be involved in the maintenance of vascular integrity. In this study we used an in vitro embryonic stem (ES) cell culture system to maintain the VEGFR-3+ endothelial cell (EC) and investigated the role of VEGFR-3 signals at the cellular level. In this system packed clusters of ECs were formed. Whereas addition of exogenous VEGF-A induced EC dispersion, VEGF-C, which can also stimulate VEGFR-2, promoted EC growth without disturbing the EC clusters. Moreover, addition of AFL4, an antagonistic MoAb for VEGFR-3, resulted in EC dispersion. Cytological analysis showed that VEGF-A– and AFL4-treated ECs were indistinguishable in many aspects but were distinct from the cytological profile induced by antagonistic MoAb for VE-cadherin (VECD-1). As AFL4- induced EC dispersion requires VEGF-A stimulation, it is likely that VEGFR-3 signals negatively modulate VEGFR-2. This result provides new insights into the involvement of VEGFR-3 signals in the maintenance of vascular integrity through modulation of VEGFR-2 signals. Moreover, our findings suggest that the mechanisms underlying AFL4-induced EC dispersion are distinct from those underlying VECD-1–induced dispersion for maintenance of EC integrity.

scholarly journals Re-Differentiation Capacity of Human Chondrocytes in Vitro Following Electrical Stimulation with Capacitively Coupled Fields

2019 ◽  
Vol 8 (11) ◽  
pp. 1771 ◽  
Author(s):  
Simone Krueger ◽  
Sophie Achilles ◽  
Julius Zimmermann ◽  
Thomas Tischer ◽  
Rainer Bader ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Electric Fields ◽  
Ex Vivo ◽  
Human Chondrocytes ◽  
Capacitively Coupled ◽  
Differentiation Capacity ◽  
Cartilage Lesions ◽  
Gene And Protein Expression ◽  
Chondrocytic Differentiation

Treatment of cartilage lesions remains a clinical challenge. Therefore, biophysical stimuli like electric fields seem to be a promising tool for chondrocytic differentiation and treatment of cartilage lesions. In this in vitro study, we evaluated the effects of low intensity capacitively coupled electric fields with an alternating voltage of 100 mVRMS (corresponds to 5.2 × 10−5 mV/cm) or 1 VRMS (corresponds to 5.2 × 10−4 mV/cm) with 1 kHz, on human chondrocytes derived from osteoarthritic (OA) and non-degenerative hyaline cartilage. A reduction of metabolic activity after electrical stimulation was more pronounced in non-degenerative cells. In contrast, DNA contents in OA cells were significantly decreased after electrical stimulation. A difference between 100 mVRMS and 1 VRMS was not detected. However, a voltage-dependent influence on gene and protein expression was observed. Both cell types showed increased synthesis rates of collagen (Col) II, glycosaminoglycans (GAG), and Col I protein following stimulation with 100 mVRMS, whereas this increase was clearly higher in OA cells. Our results demonstrated the sensitization of chondrocytes by alternating electric fields, especially at 100 mVRMS, which has an impact on chondrocytic differentiation capacity. However, analysis of further electrical stimulation parameters should be done to induce optimal hyaline characteristics of ex vivo expanded human chondrocytes.

scholarly journals Promoting osseointegration with electrical stimulation: a review

2021 ◽  
Author(s):  
Emily Pettersen ◽  
Jenna Anderson ◽  
Max Ortiz-Catalan
Keyword(s):  
Electrical Stimulation ◽  
Electric Fields ◽  
Meta Analysis ◽  
Implant Surface ◽  
Power Sources ◽  
Stimulation Parameters ◽  
Bone Quantity ◽  
Major Factors

<p>Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone-anchored implants, where osseointegration defines the biological bonding between an implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the implant-bone interface with electrical stimulation using various approaches such as different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in different <i>in vitro</i> and <i>in vivo</i> models. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using <i>in vitro</i> models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in <i>in vivo </i>investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.</p>

Promoting osseointegration with electrical stimulation: a review

2021 ◽  
Author(s):  
Emily Pettersen ◽  
Jenna Anderson ◽  
Max Ortiz-Catalan
Keyword(s):  
Electrical Stimulation ◽  
Electric Fields ◽  
Meta Analysis ◽  
Implant Surface ◽  
Power Sources ◽  
Stimulation Parameters ◽  
Bone Quantity ◽  
Major Factors

<p>Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone-anchored implants, where osseointegration defines the biological bonding between an implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the implant-bone interface with electrical stimulation using various approaches such as different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in different <i>in vitro</i> and <i>in vivo</i> models. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using <i>in vitro</i> models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in <i>in vivo </i>investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.</p>

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