Numerical Assessment of Thermal Response Associated With In Vivo Skin Electroporation: The Importance of the Composite Skin model

Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. The structure of the transport inhibiting outer layer, the stratum corneum, is temporarily destabilized due to the development of microscopic pores. Consequently agents that are ordinarily unable to pass into the skin are able to pass through this outer barrier. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with Joule heating. This paper shows the importance of using a composite model in calculating the electrical and thermal effects associated with skin electroporation. A three-dimensional transient finite-volume model of in vivo skin electroporation is developed to emphasize the importance of representing the skin’s composite layers and to illustrate the underlying relationships between the physical parameters of the composite makeup of the skin and resulting thermal damage potential.

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Numerical Modeling of In Vivo Plate Electroporation Thermal Dose Assessment

Journal of Biomechanical Engineering ◽

10.1115/1.2132375 ◽

2005 ◽

Vol 128 (1) ◽

pp. 76-84 ◽

Cited By ~ 19

Author(s):

S. M. Becker ◽

A. V. Kuznetsov

Keyword(s):

Cell Membrane ◽

Three Dimensional ◽

Dose Assessment ◽

Physical Parameters ◽

Damage Potential ◽

Plate Electrode ◽

Electric Pulses ◽

Molecule Transport ◽

Pass Through

Electroporation is an approach used to enhance the transport of large molecules to the cell cytosol in which a targeted tissue region is exposed to a series of electric pulses. The cell membrane, which normally acts as a barrier to large molecule transport into the cell interior, is temporarily destabilized due to the development of pores in the cell membrane. Consequently, agents that are ordinarily unable enter the cell are able to pass through the cell membrane. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with joule heating. This paper explores the thermal effects of various geometric, biological, and electroporation pulse parameters including the blood vessel presence and size, plate electrode configuration, and pulse duration and frequency. A three-dimensional transient finite volume model of in vivo parallel plate electroporation of liver tissue is used to develop a better understanding of the underlying relationships between the physical parameters involved with tissue electroporation and resulting thermal damage potential.

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Plate Electroporation: A Numerical Study of Factors Affecting Thermal Damage

Heat Transfer, Part B ◽

10.1115/imece2005-79540 ◽

2005 ◽

Author(s):

S. M. Becker ◽

A. V. Kuznetsov

Keyword(s):

Cell Membrane ◽

Thermal Damage ◽

Numerical Study ◽

Three Dimensional ◽

Physical Parameters ◽

Damage Potential ◽

Plate Electrode ◽

Factors Affecting ◽

Electric Pulses

Electroporation is an approach used to enhance the transport of large molecules to cell cytosol in which a targeted tissue region is exposed to a series of electric pulses. The cell membrane, which normally acts as a barrier to large molecule transport into the cell interior, is temporarily destabilized due to the development of pores in the cell membrane. Consequently agents that are ordinarily unable enter the cell are able to pass through the cell membrane. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with joule heating. This paper explores the thermal effects of various geometric, biological, and electroporation pulse parameters including the blood vessel presence and size, plate electrode configuration, and pulse duration and frequency. A three-dimensional transient finite volume model of in vivo parallel plate electroporation of liver tissue is used to develop a better understanding of the underlying relationships between the physical parameters involved with tissue electroporation and resulting thermal damage potential.

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Multi-Organs-on-Chips: Towards Long-Term Biomedical Investigations

Molecules ◽

10.3390/molecules24040675 ◽

2019 ◽

Vol 24 (4) ◽

pp. 675 ◽

Cited By ~ 22

Author(s):

Yi Zhao ◽

Ranjith Kankala ◽

Shi-Bin Wang ◽

Ai-Zheng Chen

Keyword(s):

Real Time ◽

Three Dimensional ◽

Drug Efficacy ◽

Dynamic Responses ◽

Physical Parameters ◽

Real Time Monitoring ◽

Multiple Organs ◽

On Chip

With advantageous features such as minimizing the cost, time, and sample size requirements, organ-on-a-chip (OOC) systems have garnered enormous interest from researchers for their ability for real-time monitoring of physical parameters by mimicking the in vivo microenvironment and the precise responses of xenobiotics, i.e., drug efficacy and toxicity over conventional two-dimensional (2D) and three-dimensional (3D) cell cultures, as well as animal models. Recent advancements of OOC systems have evidenced the fabrication of ‘multi-organ-on-chip’ (MOC) models, which connect separated organ chambers together to resemble an ideal pharmacokinetic and pharmacodynamic (PK-PD) model for monitoring the complex interactions between multiple organs and the resultant dynamic responses of multiple organs to pharmaceutical compounds. Numerous varieties of MOC systems have been proposed, mainly focusing on the construction of these multi-organ models, while there are only few studies on how to realize continual, automated, and stable testing, which still remains a significant challenge in the development process of MOCs. Herein, this review emphasizes the recent advancements in realizing long-term testing of MOCs to promote their capability for real-time monitoring of multi-organ interactions and chronic cellular reactions more accurately and steadily over the available chip models. Efforts in this field are still ongoing for better performance in the assessment of preclinical attributes for a new chemical entity. Further, we give a brief overview on the various biomedical applications of long-term testing in MOCs, including several proposed applications and their potential utilization in the future. Finally, we summarize with perspectives.

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A Novel 3D Scaffold for Cell Growth to Asses Electroporation Efficacy

Cells ◽

10.3390/cells8111470 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1470 ◽

Cited By ~ 3

Author(s):

Dettin ◽

Sieni ◽

Zamuner ◽

Marino ◽

Sgarbossa ◽

...

Keyword(s):

Extracellular Matrix ◽

Cell Cultures ◽

Three Dimensional ◽

Cell Interaction ◽

Growth Patterns ◽

3D Scaffold ◽

Electric Pulses ◽

Breast Carcinoma Cell Lines ◽

Cell Cell

Tumor electroporation (EP) refers to the permeabilization of the cell membrane by means of short electric pulses thus allowing the potentiation of chemotherapeutic drugs. Standard plate adhesion 2D cell cultures can simulate the in vivo environment only partially due to lack of cell–cell interaction and extracellular matrix (ECM). In this study, we assessed a novel 3D scaffold for cell cultures based on hyaluronic acid and ionic-complementary self-assembling peptides (SAPs), by studying the growth patterns of two different breast carcinoma cell lines (HCC1569 and MDA-MB231). This 3D scaffold modulates cell shape and induces extracellular matrix deposit around cells. In the MDA-MB 231 cell line, it allows three-dimensional growth of structures known as spheroids, while in HCC1569 it achieves a cell organization similar to that observed in vivo. Interestingly, we were able to visualize the electroporation effect on the cells seeded in the new scaffold by means of standard propidium iodide assay and fluorescence microscopy. Thanks to the presence of cell–cell and cell–ECM interactions, the new 3D scaffold may represent a more reliable support for EP studies than 2D cancer cell cultures and may be used to test new EP-delivered drugs and novel EP protocols.

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An Improved Thermal-Resistance-Capacitance Model for Vertical Single U-Tube Ground Heat Exchanger

Journal of Thermal Science and Engineering Applications ◽

10.1115/1.4041437 ◽

2018 ◽

Vol 11 (1) ◽

Author(s):

Quan Liao ◽

Yongxiang Fan ◽

Xiaobo Zhu ◽

Jintang Li

Keyword(s):

Heat Exchanger ◽

Thermal Resistance ◽

Finite Volume ◽

Three Dimensional ◽

Thermal Response ◽

Data Interpretation ◽

Physical Parameters ◽

Ground Heat Exchanger ◽

Cfd Model ◽

Capacitance Model

Abstract Based on four-thermal-resistance-capacitance network within a borehole, an improved thermal-resistance-capacitance model (TRCM), which takes into account the effect of nonuniform temperature distribution along the borehole perimeter, is proposed for vertical single U-tube ground heat exchanger. For a given geometric and physical parameters of ground heat exchanger, the numerical simulations of the conventional TRCM based on three-thermal-resistance-capacitance network within borehole, the improved TRCM based on four-thermal-resistance-capacitance network within borehole and three-dimensional (3D) finite volume computational fluid dynamics (CFD) model by using fluent software were conducted, respectively. Through the comprehensive comparisons of simulation results between these above-mentioned three models for vertical single U-tube ground heat exchanger, it could be concluded that the proposed improved TRCM could not only provide relatively high accurate results, but also remarkably decrease the solving time as compared to the benchmark 3D finite volume CFD model. Since the proposed TRCM has better performance than the one based on three-thermal-resistance-capacitance network within borehole and 3D finite volume CFD model, a new reliable and feasible TRCM for vertical single U-tube ground heat exchanger could be available for the design and optimization of ground heat exchanger, the data interpretation of thermal response test (TRT) and other applications of ground heat exchanger in real industrial engineering.

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Collagen Receptor-Mediated Mechanochemical Signaling Contributes to Human Pro-Angiogenic Mesenchymal Stem/Progenitor Cell-Induced Neo-Vasculogenesis

Blood ◽

10.1182/blood.v120.21.5196.5196 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5196-5196

Author(s):

Mario Gimona ◽

Rokhsareh Rohban ◽

Thomas Lener ◽

Doris Peckl-Schmid ◽

Michaela Oeller ◽

...

Keyword(s):

Progenitor Cells ◽

Conflicts Of Interest ◽

Three Dimensional ◽

Cell Types ◽

Antibody Array ◽

Physical Parameters ◽

Mrna Levels ◽

The Matrix ◽

Culture Strategies

Abstract Abstract 5196 Background and rationale Human mesenchymal stem/progenitor cells (MSPCs) are important tools for tissue repair and regenerative approaches. Co-application of autologous pairs of human MSPCs and endothelial colony forming progenitor cells (ECFCs) drives vessel formation in a mouse model. However, a more detailed mechanistic insight into the contribution of MSPCs to vasculogenesis is required prior to a potential application in clinical trials. The formation of perfused blood vessels following the co-injection of MSPC/ECFC pairs requires directed migration of these cell types through the extracellular matrix. For this, cells must interpret and respond to both biochemical cues and physical parameters of the matrix. Here we aimed at identifying changes in early signaling molecules that could potentially mediate these complex behaviors in ECFCs and MSPCs. Results By antibody array analysis of biopsies from vasculogenic regions we identified the levels of the discoidin domain receptor 2 (DDR2) to be upregulated about twofold in MSPCs in an MSPC/ECFC mixture compared to MSPC-only implants. Expression of DDR2 was confirmed by flow cytometry analysis. Employing immunofluorescence microscopy we showed components of the mechanotransduction and cytoskeleton machinery (Paxillin, ILK, Src, h1CaP, and cortactin) to be abundantly expressed and correctly localized in MSPCs. MSPCs also responded to manipulation of cytoskeletal integrity with phorbol dibutyrate or Y-27632, demonstrating the presence of a tissue transmigration machinery in MSPCs. Applying various three dimensional cell culture strategies we identified significant alterations in MSPC morphology, as well as in the mRNA levels for DDR1 and DDR2, and for miRNAs 29b, 199a, 331 in response to different matrix conditions. Conclusions Our data suggest a mechanosensitive regulation of MSPC function and we thus conclude that direct or indirect (miRNA-mediated) regulation of the collagen receptors DDR1/2 could have a role in modulating MSPC function during stem-cell induced neo-vascularization in vivo. Disclosures: No relevant conflicts of interest to declare.

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In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100083035 ◽

1978 ◽

Vol 36 (2) ◽

pp. 434-435

Author(s):

D. Reis ◽

B. Vian ◽

J. C. Roland

Keyword(s):

Cell Wall ◽

Self Assembly ◽

Plant Cell Wall ◽

Higher Plants ◽

Three Dimensional ◽

Cytochemical Study ◽

Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

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Three-Dimensional Subcellular Organization of Hepatocytes in Intact Liver: Simultaneous Visualization of Cytoskeletal and Membrane Markers by Confocal Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100163903 ◽

1996 ◽

Vol 54 ◽

pp. 288-289

Author(s):

Greg V. Martin ◽

Ann L. Hubbard

Keyword(s):

Three Dimensional ◽

Integral Membrane Proteins ◽

Polarized Secretion ◽

Microscope Images ◽

Computer Aided ◽

Intracellular Organelles ◽

Cytoskeletal Elements ◽

Simultaneous Visualization

The microtubule (MT) cytoskeleton is necessary for many of the polarized functions of hepatocytes. Among the functions dependent on the MT-based cytoskeleton are polarized secretion of proteins, delivery of endocytosed material to lysosomes, and transcytosis of integral plasma membrane (PM) proteins. Although microtubules have been shown to be crucial to the establishment and maintenance of functional and structural polarization in the hepatocyte, little is known about the architecture of the hepatocyte MT cytoskeleton in vivo, particularly with regard to its relationship to PM domains and membranous organelles. Using an in situ extraction technique that preserves both microtubules and cellular membranes, we have developed a protocol for immunofluorescent co-localization of cytoskeletal elements and integral membrane proteins within 20 µm cryosections of fixed rat liver. Computer-aided 3D reconstruction of multi-spectral confocal microscope images was used to visualize the spatial relationships among the MT cytoskeleton, PM domains and intracellular organelles.

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