Nonthermal Irreversible Electroporation for Tissue Decellularization

2010 ◽  
Vol 132 (9) ◽  
Author(s):  
Mary Phillips ◽  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Electrical Parameters ◽  
Irreversible Damage ◽  
Tissue Scaffold ◽  
Electrical Fields ◽  
Nonthermal Irreversible Electroporation ◽  
Tissue Scaffolding ◽  
Living Tissues

Tissue scaffolding is a key component for tissue engineering, and the extracellular matrix (ECM) is nature’s ideal scaffold material. A conceptually different method is reported here for producing tissue scaffolds by decellularization of living tissues using nonthermal irreversible electroporation (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the cell membrane in the targeted tissue while sparing the ECM and utilizing the body’s host response for decellularization. This study demonstrates that the method preserves the native tissue ECM and produces a scaffold that is functional and facilitates recellularization. A two-dimensional transient finite element solution of the Laplace and heat conduction equations was used to ensure that the electrical parameters used would not cause any thermal damage to the tissue scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in 3 days post NTIRE the immune system decellularizes the irreversible electroporated tissue and leaves behind a functional scaffold. In 7 days, there is evidence of endothelial regrowth, indicating that the artery scaffold maintained its function throughout the procedure and normal recellularization is taking place.

scholarly journals Hyperspectral Imagery for Assessing Laser-Induced Thermal State Change in Liver

Sensors ◽  
2021 ◽  
Vol 21 (2) ◽  
pp. 643
Author(s):  
Martina De Landro ◽  
Ignacio Espíritu García-Molina ◽  
Manuel Barberio ◽  
Eric Felli ◽  
Vincent Agnus ◽  
...  
Keyword(s):  
Thermal Damage ◽  
Thermal State ◽  
Preliminary Investigation ◽  
Spectral Band ◽  
Spectral Variation ◽  
Ablation Therapy ◽  
Clinical Endpoints ◽  
Breathing Motion ◽  
Living Tissues

This work presents the potential of hyperspectral imaging (HSI) to monitor the thermal outcome of laser ablation therapy used for minimally invasive tumor removal. Our main goal is the establishment of indicators of the thermal damage of living tissues, which can be used to assess the effect of the procedure. These indicators rely on the spectral variation of temperature-dependent tissue chromophores, i.e., oxyhemoglobin, deoxyhemoglobin, methemoglobin, and water. Laser treatment was performed at specific temperature thresholds (from 60 to 110 °C) on in-vivo animal liver and was assessed with a hyperspectral camera (500–995 nm) during and after the treatment. The indicators were extracted from the hyperspectral images after the following processing steps: the breathing motion compensation and the spectral and spatial filtering, the selection of spectral bands corresponding to specific tissue chromophores, and the analysis of the areas under the curves for each spectral band. Results show that properly combining spectral information related to deoxyhemoglobin, methemoglobin, lipids, and water allows for the segmenting of different zones of the laser-induced thermal damage. This preliminary investigation provides indicators for describing the thermal state of the liver, which can be employed in the future as clinical endpoints of the procedure outcome.

scholarly journals A Study on Nonthermal Irreversible Electroporation of the Thyroid

2019 ◽  
Vol 18 ◽  
pp. 153303381987630
Author(s):  
Yanpeng Lv ◽  
Yanfang Zhang ◽  
Jianwei Huang ◽  
Yunlong Wang ◽  
Boris Rubinsky
Keyword(s):  
Electric Fields ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Pulse Sequences ◽  
Cell Swelling ◽  
Tissue Type ◽  
Heterogeneous Structure ◽  
Treatment Protocols ◽  
Thyroid Ablation ◽  
Nonthermal Irreversible Electroporation

Background: Nonthermal irreversible electroporation is a minimally invasive surgery technology that employs high and brief electric fields to ablate undesirable tissues. Nonthermal irreversible electroporation can ablate only cells while preserving intact functional properties of the extracellular structures. Therefore, nonthermal irreversible electroporation can be used to ablate tissues safely near large blood vessels, the esophagus, or nerves. This suggests that it could be used for thyroid ablation abutting the esophagus. This study examines the feasibility of using nonthermal irreversible electroporation for thyroid ablation. Methods: Rats were used to evaluate the effects of nonthermal irreversible electroporation on the thyroid. The procedure entails the delivery of high electric field pulses (1-3 kV/cm, 100 microseconds) between 2 surface electrodes bracing the thyroid. The right lobe was treated with various nonthermal irreversible electroporation pulse sequences, and the left was the control. After 24 hours of the nonthermal irreversible electroporation treatment, the thyroid was examined with hemotoxylin and eosin histological analysis. Mathematical models of electric fields and the Joule heating-induced temperature raise in the thyroid were developed to examine the experimental results. Results: Treatment with nonthermal irreversible electroporation leads to follicular cells damage, associated with cell swelling, inflammatory cell infiltration, and cell ablation. Nonthermal irreversible electroporation spares the trachea structure. Unusually high electric fields, for these types of tissue, 3000 V/cm, are needed for thyroid ablation. The mathematical model suggests that this may be related to the heterogeneous structure of the thyroid-induced distortion of local electric fields. Moreover, most of the tissue does not experience thermal damage inducing temperature elevation. However, the heterogeneous structure of the thyroid may cause local hot spots with the potential for local thermal damage. Conclusion: Nonthermal irreversible electroporation with 3000 V/cm can be used for thyroid ablation. Possible applications are treatment of hyperthyroidism and thyroid cancer. The highly heterogeneous structure of the thyroid distorts the electric fields and temperature distribution in the thyroid must be considered when designing treatment protocols for this tissue type.

Endovascular Nonthermal Irreversible Electroporation: A Finite Element Analysis

2010 ◽  
Vol 132 (3) ◽  
Author(s):  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Finite Element ◽  
Electric Field ◽  
Electric Fields ◽  
Joule Heating ◽  
Arterial Wall ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Phospholipid Bilayer ◽  
Tissue Ablation ◽  
Nonthermal Irreversible Electroporation

Tissue ablation finds an increasing use in modern medicine. Nonthermal irreversible electroporation (NTIRE) is a biophysical phenomenon and an emerging novel tissue ablation modality, in which electric fields are applied in a pulsed mode to produce nanoscale defects to the cell membrane phospholipid bilayer, in such a way that Joule heating is minimized and thermal damage to other molecules in the treated volume is reduced while the cells die. Here we present a two-dimensional transient finite element model to simulate the electric field and thermal damage to the arterial wall due to an endovascular NTIRE novel device. The electric field was used to calculate the Joule heating effect, and a transient solution of the temperature is presented using the Pennes bioheat equation. This is followed by a kinetic model of the thermal damage based on the Arrhenius formulation and calculation of the Henriques and Moritz thermal damage integral. The analysis shows that the endovascular application of 90, 100 μs pulses with a potential difference of 600 V can induce electric fields of 1000 V/cm and above across the entire arterial wall, which are sufficient for irreversible electroporation. The temperature in the arterial wall reached a maximum of 66.7°C with a pulse frequency of 4 Hz. Thermal damage integral showed that this protocol will thermally damage less than 2% of the molecules around the electrodes. In conclusion, endovascular NTIRE is possible. Our study sets the theoretical basis for further preclinical and clinical trials with endovascular NTIRE.

Intracranial Nonthermal Irreversible Electroporation: In Vivo Analysis

2010 ◽  
Vol 236 (1) ◽  
pp. 127-136 ◽  
Author(s):  
Paulo A. Garcia ◽  
John H. Rossmeisl ◽  
Robert E. Neal ◽  
Thomas L. Ellis ◽  
John D. Olson ◽  
...  
Keyword(s):  
Irreversible Electroporation ◽  
Nonthermal Irreversible Electroporation ◽  
In Vivo Analysis

Irreversible Electroporation: An In Vivo Study Within the Dorsal Skin Fold Chamber

2011 ◽  
Author(s):  
Zhenpeng Qin ◽  
Jing Jiang ◽  
Gary Long ◽  
John C. Bischof
Keyword(s):  
Protein Denaturation ◽  
Irreversible Electroporation ◽  
Molecular Transport ◽  
Electrical Field ◽  
Irreversible Damage ◽  
Skin Fold ◽  
Electrical Pulses ◽  
Dorsal Skin Fold Chamber ◽  
Fast Procedure

Electroporation has been traditionally used to enhance molecular transport into cells (e.g. gene therapy) and through tissues (e.g. skin) by creating reversible pores with short electrical pulses [1]. Increasing the parameters (electrical field, pulse duration and number) can induce irreversible damage to the cells and tissue. Recently, irreversible electroporation (IRE) has been investigated as a new tumor ablation method [2]. The advantages of the IRE include the simple and fast procedure (train of μs pulses), sharp demarcation between treated and untreated regions, destruction of tumor cells while preserving the connective tissue, and minimal effect of immune response on treatment efficacy [3]. The unique interaction of electrical field with heterogeneous structures prevents damage to nerves, blood vessels and ducts [4]. IRE has been claimed to produce negligible thermal injury and protein denaturation typical to thermal ablation [5]. However, how each electroporation parameter in IRE affects tumor destruction and the possibility of heating remains to be studied in tumors vivo.

Electrical Field and Temperature Model of Nonthermal Irreversible Electroporation in Heterogeneous Tissues

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Charlotte Daniels ◽  
Boris Rubinsky
Keyword(s):  
Blood Vessels ◽  
Irreversible Electroporation ◽  
Surrounding Tissue ◽  
Electrical Field ◽  
Irreversible Damage ◽  
Minimally Invasive Surgical ◽  
Dimensional Finite Element ◽  
Nonthermal Irreversible Electroporation ◽  
Molecular Surgery ◽  
Heterogeneous Tissues

Nonthermal irreversible electroporation (NTIRE) is a new minimally invasive surgical technique that is part of the emerging field of molecular surgery, which holds the potential to treat diseases with unprecedented accuracy. NTIRE utilizes electrical pulses delivered to a targeted area, producing irreversible damage to the cell membrane. Because NTIRE does not cause thermal damage, the integrity of all other molecules, collagen, and elastin in the targeted area is preserved. Previous theoretical studies have only examined NTIRE in homogeneous tissues; however, biological structures are complex collections of diverse tissues. In order to develop electroporation as a precise treatment in clinical applications, realistic models are necessary. Therefore, the purpose of this study was to refine electroporation as a treatment by examining the effect of NTIRE in heterogeneous tissues of the prostate and breast. This study uses a two-dimensional finite element solution of the Laplace and bioheat equations to examine the effects of heterogeneities on electric field and temperature distribution. Three different heterogeneous structures were taken into account: nerves, blood vessels, and ducts. The results of this study demonstrate that heterogeneities significantly impact both the temperature and electrical field distribution in surrounding tissues, indicating that heterogeneities should not be neglected. The results were promising. While the surrounding tissue experienced a high electrical field, the axon of the nerve, the interior of the blood vessel, and the ducts experienced no electrical field. This indicates that blood vessels, nerves, and lactiferous ducts adjacent to a tumor treated with electroporation will survive, while the cancerous lesion is ablated. This study clearly demonstrates the importance of considering heterogeneity in NTIRE applications.

A Preliminary Study to Delineate Irreversible Electroporation From Thermal Damage Using the Arrhenius Equation

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Hadi Shafiee ◽  
Paulo A. Garcia ◽  
Rafael V. Davalos
Keyword(s):  
Physical Properties ◽  
Upper Bound ◽  
Thermal Damage ◽  
Electric Pulse ◽  
Irreversible Electroporation ◽  
Human Monocyte ◽  
Electrical Fields ◽  
Reversible Electroporation ◽  
Electrical Pulses ◽  
Pulse Characteristics

Intense but short electrical fields can increase the permeability of the cell membrane in a process referred to as electroporation. Reversible electroporation has become an important tool in biotechnology and medicine. The various applications of reversible electroporation require cells to survive the procedure, and therefore the occurrence of irreversible electroporation (IRE), following which cells die, is obviously undesirable. However, for the past few years, IRE has begun to emerge as an important minimally invasive nonthermal ablation technique in its own right as a method to treat tumors and arrhythmogenic regions in the heart. IRE had been studied primarily to define the upper limit of electrical parameters that induce reversible electroporation. Thus, the delineation of IRE from thermal damage due to Joule heating has not been thoroughly investigated. The goal of this study was to express the upper bound of IRE (onset of thermal damage) theoretically as a function of physical properties and electrical pulse parameters. Electrical pulses were applied to THP-1 human monocyte cells, and the percentage of irreversibly electroporated (dead) cells in the sample was quantified. We also determined the upper bound of IRE (onset of thermal damage) through a theoretical calculation that takes into account the physical properties of the sample and the electric pulse characteristics. Our experimental results were achieved below the theoretical curve for the onset of thermal damage. These results confirm that the region to induce IRE without thermal damage is substantial. We believe that our new theoretical analysis will allow researchers to optimize IRE parameters without inducing deleterious thermal effects.

Principles of Tissue Engineering With Nonthermal Irreversible Electroporation

2010 ◽  
Vol 133 (1) ◽  
Author(s):  
Mary Phillips ◽  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Electric Fields ◽  
Irreversible Electroporation ◽  
Membrane Lipid ◽  
Element Analysis ◽  
Tissue Scaffold ◽  
Invasive Approach ◽  
Electric Pulses ◽  
Thermal Fields ◽  
Nonthermal Irreversible Electroporation ◽  
Electric Parameters

Nonthermal irreversible electroporation (NTIRE) is an emerging tissue ablation modality that may be ideally suited in developing a decellularized tissue graft. NTIRE utilizes short electric pulses that produce nanoscale defects in the cell membrane lipid bilayer. The electric parameters can be chosen in such a way that Joule heating to the tissue is minimized and cell death occurs solely due to loss in cell homeostasis. By coupling NTIRE with the body’s response, the cells can be selectively ablated and removed, leaving behind a tissue scaffold. Here, we introduce two different methods for developing a decellularized arterial scaffold. The first uses an electrode clamp that is applied to the outside of a rodent carotid artery and the second applies an endovascular minimally invasive approach to apply electric fields from the inner surface of the blood vessels. Both methods are first modeled using a transient finite element analysis of electric and thermal fields to ensure that the electric parameters used in this study will result in minimal thermal damage. Experimental work demonstrates that both techniques result in not only a decellularized arterial construct but an endothelial regrowth is evident along the lumen 7 days after treatment, indicating that the extracellular matrix was not damaged by electric and thermal fields and is still able to support cell growth.

scholarly journals Survival and Proliferation under Severely Hypoxic Microenvironments Using Cell-Laden Oxygenating Hydrogels

2021 ◽  
Vol 12 (2) ◽  
pp. 30
Author(s):  
Shabir Hassan ◽  
Berivan Cecen ◽  
Ramon Peña-Garcia ◽  
Fernanda Roberta Marciano ◽  
Amir K. Miri ◽  
...  
Keyword(s):  
Prolonged Release ◽  
Therapeutic Approaches ◽  
Encapsulated Cells ◽  
Hypoxic Conditions ◽  
Skeletal Myoblasts ◽  
Artificial Tissue ◽  
Delivery Platform ◽  
Living Tissues

Different strategies have been employed to provide adequate nutrients for engineered living tissues. These have mainly revolved around providing oxygen to alleviate the effects of chronic hypoxia or anoxia that result in necrosis or weak neovascularization, leading to failure of artificial tissue implants and hence poor clinical outcome. While different biomaterials have been used as oxygen generators for in vitro as well as in vivo applications, certain problems have hampered their wide application. Among these are the generation and the rate at which oxygen is produced together with the production of the reaction intermediates in the form of reactive oxygen species (ROS). Both these factors can be detrimental for cell survival and can severely affect the outcome of such studies. Here we present calcium peroxide (CPO) encapsulated in polycaprolactone as oxygen releasing microparticles (OMPs). While CPO releases oxygen upon hydrolysis, PCL encapsulation ensures that hydrolysis takes place slowly, thereby sustaining prolonged release of oxygen without the stress the bulk release can endow on the encapsulated cells. We used gelatin methacryloyl (GelMA) hydrogels containing these OMPs to stimulate survival and proliferation of encapsulated skeletal myoblasts and optimized the OMP concentration for sustained oxygen delivery over more than a week. The oxygen releasing and delivery platform described in this study opens up opportunities for cell-based therapeutic approaches to treat diseases resulting from ischemic conditions and enhance survival of implants under severe hypoxic conditions for successful clinical translation.

Persistent Luminescence Cr3+ Doped Spinels and Use as Biomarker for In Vivo Imaging

2014 ◽  
Vol 90 ◽  
pp. 157-165
Author(s):  
Suchinder K. Sharma ◽  
D. Gourier ◽  
B. Viana ◽  
T. Maldiney ◽  
E. Teston ◽  
...  
Keyword(s):  
Uv Light ◽  
Red Light ◽  
Band Gap Energy ◽  
Transparency Window ◽  
Persistent Luminescence ◽  
High Brightness ◽  
Mouse Imaging ◽  
Classical Quantum ◽  
Living Tissues

ZnGa2O4(ZGO) is a normal spinel. When doped with Cr3+ions, ZGO:Cr becomes a high brightness persistent luminescence material with an emission spectrum perfectly matching the transparency window of living tissues. It allowsin vivomouse imaging with a better signal to background ratio than classical quantum dots. The most interesting characteristic of ZGO:Cr lies in the fact that its LLP can be excited with red light, well below its band gap energy and in the transparency window of living tissues. A mechanism based on the trapping of carriers localized around a special type of Cr3+ions namely CrN2can explain this singularity. The antisite defects of the structure are the main responsible traps in the persistent luminescence mechanism. When located around Cr3+ions, they allow, via Cr3+absorption, the storage of not only UV light but also all visible light from the excitation source.

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