Search results for: tissue engineering scaffold
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4334

Search results for: tissue engineering scaffold

4184 The Effect of Jujube Extract and Resistance Training on the Reduction of Complications Caused by the Induction of Anabolic Steroid Boldenone on the Histopathological Changes of Pancreatic Tissue of Male Wistar Rats

Authors: Sayyed-javad Ziaolhagh, Ali-Reza Saadatifar

Abstract:

Introduction: Athletes frequently perform anabolic steroid resistance exercise, but the effects of medical doses and abuse along with resistance exercise on structural damage to the Pancreases and also jujube extract are unknown. The aim of this study was to investigate the effects of resistance training on body weight and hip fractures induced by boldenone injection in male rats. Materials and methods: In this experimental study, 30 male Wistar rats aged 8-12 weeks (weight 202±9.34 g) were randomly divided into five groups: control, boldenone, extract of iujuba+boldenone, boldenone+resistance training and boldenone+resistance training +extract of jujuba. The resistance training program included climbing the ladder for 8 weeks, 3 days a week, 1 session training in a day and each session consisted of the 3 sets and 5 repetitions. Injection was conducted in depth in the hamstring once a week on an appointed day. After anesthesia, autopsy was performed, and the cardiac tissue was isolated. Results: Results showed that boldenone caused tissue damage, congestion, and nuclei unclear and diffuse. In the group "resistance + Boldenone," The Pancreases tissue showed a high degree of hyperemia, and the muscle cells were somewhat abnormal. In boldenone + jujube, the appearance of the tissue was normal, and the rejuvenating effect was visible. Conclusion: Boldenone appears to cause structural damage to the Pancreases tissue. Strength training with Jujube Extract can reduce part of the pancreatic system disorders (necrosis and inflammation) caused by anabolic steroid use.

Keywords: boldenone, Jujube extract, pancreases tissue, resistance training

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4183 Stroma-Providing Activity of Adipose Derived Mesenchymal Stromal Cells in Tissue-Related O2 Microenvironment

Authors: P. I. Bobyleva, E. R. Andreeva, I. V. Andrianova, E. V. Maslova, L. B. Buravkova

Abstract:

This work studied the ability of adipose tissue-derived mesenchymal stromal cells (MSCs) to form stroma for expansion of cord blood hematopoietic cells. We showed that 72-hour interaction of MSCs with cord blood mononuclear cells (MNCs) in vitro at atmospheric (20%) and low (5%) O2 conditions increased the expression of ICAM-1, HCAM (at the beginning of interaction) on MSCs. Viability of MSCs and MNCs were maintained at high level. Adhesion of MNCs to MSCs was faster at 20% O2. MSCs promoted the proliferation of adhered MNCs to form the suspension containing great number of hematopoietic colony-forming units, and this effect was more pronounced at 5% O2. Thus, adipose-derived MSCs supplied sufficient stromal support to cord blood MNCs both at 20% and 5% О2, providing their adhesion with further expansion of new generation of different hematopoietic lineages.

Keywords: hematopoietic stem and progenitor cells, mesenchymal stromal cells, tissue-related oxygen, adipose tissue

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4182 An Exploration of the Pancreatic Cancer miRNome during the Progression of the Disease

Authors: Barsha Saha, Shouvik Chakravarty, Sukanta Ray, Kshaunish Das, Nidhan K. Biswas, Srikanta Goswami

Abstract:

Pancreatic Ductal Adenocarcinoma is a well-recognised cause of cancer death with a five-year survival rate of about 9%, and its incidence in India has been found to be increased manifold in recent years. Due to delayed detection, this highly metastatic disease has a poor prognosis. Several molecular alterations happen during the progression of the disease from pre-cancerous conditions, and many such alterations could be investigated for their biomarker potential. MicroRNAs have been shown to be prognostic for PDAC patients in a variety of studies. We hereby used NGS technologies to evaluate the role of small RNA changes during pancreatic cancer development from chronic pancreatitis. Plasma samples were collected from pancreatic cancer patients (n=16), chronic pancreatitis patients (n=8), and also from normal individuals (n=16). Pancreatic tumour tissue (n=5) and adjacent normal tissue samples (n=5) were also collected. Sequencing of small RNAs was carried out after small RNAs were isolated from plasma samples and tissue samples. We find that certain microRNAs are highly deregulated in pancreatic cancer patients in comparison to normal samples. A combinatorial analysis of plasma and tissue microRNAs and subsequent exploration of their targets and altered molecular pathways could not only identify potential biomarkers for disease diagnosis but also help to understand the underlying mechanism.

Keywords: small RNA sequencing, pancreatic cancer, biomarkers, tissue sample

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4181 Gellan Gum/Gamma-Polyglutamic Acid and Glycerol Composited Membrane for Guiding Bone Regeneration

Authors: Chi-Chang Lin, Jiun-Yan Chiu

Abstract:

Periodontal disease, oral cancer relating trauma is the prominent factor devastating bone tissue that is crucial to reestablishing in clinical. As we know, common symptom, osteoporosis, and infection limiting the ability of the bone tissue to recover cause difficulty before implantation therapy. Regeneration of bone tissue is the fundamental therapy before surgical processes. To promote the growth of bone tissue, many commercial products still have sophisticated problems that need to overcome. Regrettably, there is no available material which is apparently preferable for releasing and controlling of loading dosage, or mitigating inflammation. In our study, a hydrogel-based composite membrane has been prepared by using Gellan gum (GG), gamma-polyglutamic acid (γ-PGA) and glycerol with simple sol-gel method. GG is a natural material that is massively adopted in cartilage. Unfortunately, the strength of pure GG film is a manifest weakness especially under simulating body fluidic conditions. We utilize another biocompatible material, γ-PGA as cross-linker which can form tri-dimension structure that enhancing the strength. Our result indicated the strength of pure GG membrane can be obviously improved by cross-linked with γ-PGA (0.5, 0.6, 0.7, 0.8, 0.9, 1.0 w/v%). Besides, blending with glycerol (0, 1.0, 2.0, 3.0 w/v%) can significantly improve membrane toughness that corresponds to practical use. The innovative composited hydrogel made of GG, γ-PGA, and glycerol is attested with neat results including elongation and biocompatibility that take the advantage of extension covering major trauma. Recommendations are made for treatment to build up the foundation of bone tissue that would help patients to escape from the suffering and shorten the amount of time in recovery.

Keywords: bone tissue, gellan gum, regeneration, toughness

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4180 Mechanical Characterization of Brain Tissue in Compression

Authors: Abbas Shafiee, Mohammad Taghi Ahmadian, Maryam Hoviattalab

Abstract:

The biomechanical behavior of brain tissue is needed for predicting the traumatic brain injury (TBI). Each year over 1.5 million people sustain a TBI in the USA. The appropriate coefficients for injury prediction can be evaluated using experimental data. In this study, an experimental setup on brain soft tissue was developed to perform unconfined compression tests at quasistatic strain rates ∈0.0004 s-1 and 0.008 s-1 and 0.4 stress relaxation test under unconfined uniaxial compression with ∈ 0.67 s-1 ramp rate. The fitted visco-hyperelastic parameters were utilized by using obtained stress-strain curves. The experimental data was validated using finite element analysis (FEA) and previous findings. Also, influence of friction coefficient on unconfined compression and relaxation test and effect of ramp rate in relaxation test is investigated. Results of the findings are implemented on the analysis of a human brain under high acceleration due to impact.

Keywords: brain soft tissue, visco-hyperelastic, finite element analysis (FEA), friction, quasistatic strain rate

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4179 A Novel Co-Culture System for the Cementoblastic Differentiation of SHED

Authors: Manal Farea, Adam Husein, Ahmad S. Halim, Zurairah Berahim, Nurul A. Abdullah, Khairani I. Mokhtar, Kasmawati Mokhtar

Abstract:

Endodontic furcal perforation remains both an endodontic and a periodontal problem. Regeneration of cementum is very essential for the perforation repair. The aim of this study was to investigate the role of Hertwig's epithelial root sheath (HERS) cells on the cementogenic differentiation of stem cells derived from human exfoliated deciduous teeth (SHED) in the presence of chitosan scaffold-TGFβ1. HERS cells were isolated and characterized then co-cultured with SHED with/without chitosan scaffold-TGFβ1. SHED proliferation was assessed by PrestoBlue. Alkaline phosphatase activity, mineralization behaviour and gene/protein expression of cemento/osteoblast phenotype of SHED were evaluated. Results of the present study showed that HERS cells in association with chitosan-TGFβ1 enhanced proliferation and cemento/osteogenic differentiation of SHED. Our novel co-culture system confirmed the potential effect of HERS cells to stimulate the differentiation of SHED along the cementoblastic lineage which was triggered in the presence of chitosan-TGFβ1. This approach possesses a novel therapeutic strategy for future endodontic perforation and periodontitis.

Keywords: cementogenesis, co-culture system, HERS, SHED

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4178 Accumulation of Phlorotannins in Abalone Haliotis discus Hannai after Feeding with Eisenia bicyclis

Authors: Bangoura Issa, Ji-Young Kang, M. T. H. Chowdhury, Ji-Eun Lee, Yong-Ki Hong

Abstract:

Investigation was carried out for the production of value-added abalone Haliotis discus hannai containing bioactive phlorotannin by feeding phlorotannin-rich seaweed Eisenia bicyclis 2 weeks prior to harvesting. Accumulation of phlorotannins was proceded by feeding with E. bicyclis after 4 days of starvation. HPLC purification afforded two major phlorotannins. Mass spectrometry and 1H-nuclear magnetic resonance analysis clarified their structures to be as 7-phloroeckol and eckol. Throughout the feeding period of 20 days, 7-phloroeckolol was accumulated in the muscle (foot muscle tissue) up to 0.18±0.12 mg g-1 dry weight of tissue after 12 days. Eckol reached 0.21±0.03 mg g-1 dry weight of tissue after 18 days. By feeding Laminaria japonica as reference, abalone showed no detection of phlorotannins in the muscle tissue. Seaweed consumption and growth rate of abalone revealed almost similar when feed with E. bicyclis or L. japonicain 20 days. Phlorotannins reduction to half-maximal accumulation values took 1.0 day and 2.7 days for 7-phloroeckol and eckol respectively, after replacing the feed to L. japonica.

Keywords: abalone, accumulation, eisenia bicyclis, phlorotannins

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4177 Treatment of Neuronal Defects by Bone Marrow Stem Cells Differentiation to Neuronal Cells Cultured on Gelatin-PLGA Scaffolds Coated with Nano-Particles

Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

Abstract:

Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

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4176 Dynamic Behavior of Brain Tissue under Transient Loading

Authors: Y. J. Zhou, G. Lu

Abstract:

In this paper, an analytical study is made for the dynamic behavior of human brain tissue under transient loading. In this analytical model the Mooney-Rivlin constitutive law is coupled with visco-elastic constitutive equations to take into account both the nonlinear and time-dependent mechanical behavior of brain tissue. Five ordinary differential equations representing the relationships of five main parameters (radial stress, circumferential stress, radial strain, circumferential strain, and particle velocity) are obtained by using the characteristic method to transform five partial differential equations (two continuity equations, one motion equation, and two constitutive equations). Analytical expressions of the attenuation properties for spherical wave in brain tissue are analytically derived. Numerical results are obtained based on the five ordinary differential equations. The mechanical responses (particle velocity and stress) of brain are compared at different radii including 5, 6, 10, 15 and 25 mm under four different input conditions. The results illustrate that loading curves types of the particle velocity significantly influences the stress in brain tissue. The understanding of the influence by the input loading cures can be used to reduce the potentially injury to brain under head impact by designing protective structures to control the loading curves types.

Keywords: analytical method, mechanical responses, spherical wave propagation, traumatic brain injury

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4175 Use of 3D Printed Bioscaffolds from Decellularized Umbilical Cord for Cartilage Regeneration

Authors: Tayyaba Bari, Muhammad Hamza Anjum, Samra Kanwal, Fakhera Ikram

Abstract:

Osteoarthritis, a degenerative condition, affects more than 213 million individuals globally. Since articular cartilage has no or limited vessels, therefore, after deteriorating, it is unable to rejuvenate. Traditional approaches for cartilage repair, like autologous chondrocyte implantation, microfracture and cartilage transplantation are often associated with postoperative complications and lead to further degradation. Decellularized human umbilical cord has gained interest as a viable treatment for cartilage repair. Decellularization removes all cellular contents as well as debris, leaving a biologically active 3D network known as extracellular matrix (ECM). This matrix is biodegradable, non-immunogenic and provides a microenvironment for homeostasis, growth and repair. UC derived bioink function as 3D scaffolding material, not only mediates cell-matrix interactions but also adherence, proliferation and propagation of cells for 3D organoids. This study comprises different physical, chemical and biological approaches to optimize the decellularization of human umbilical cord (UC) tissues followed by the solubilization of these tissues to bioink formation. The decellularization process consisted of two cycles of freeze thaw where the umbilical cord at -20˚C was thawed at room temperature followed by dissection in small sections from 0.5 to 1cm. Similarly decellularization with ionic and non-ionic detergents Sodium dodecyl sulfate (SDS) and Triton-X 100 revealed that both concentrations of SDS i.e 0.1% and 1% were effective in complete removal of cells from the small UC tissues. The results of decellularization was further confirmed by running them on 1% agarose gel. Histological analysis revealed the efficacy of decellularization, which involves paraffin embedded samples of 4μm processed for Hematoxylin-eosin-safran and 4,6-diamidino-2-phenylindole (DAPI). ECM preservation was confirmed by Alcian Blue, and Masson’s trichrome staining on consecutive sections and images were obtained. Sulfated GAG’s content were determined by 1,9-dimethyl-methylene blue (DMMB) assay, similarly collagen quantification was done by hydroxy proline assay. This 3D bioengineered scaffold will provide a typical atmosphere as in the extracellular matrix of the tissue, which would be seeded with the mesenchymal cells to generate the desired 3D ink for in vitro and in vivo cartilage regeneration applications.

Keywords: umbilical cord, 3d printing, bioink, tissue engineering, cartilage regeneration

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4174 Osteogenesis in Thermo-Sensitive Hydrogel Using Mesenchymal Stem Cell Derived from Human Turbinate

Authors: A. Reum Son, Jin Seon Kwon, Seung Hun Park, Hai Bang Lee, Moon Suk Kim

Abstract:

These days, stem cell therapy is focused on for promising source of treatment in clinical human disease. As a supporter of stem cells, in situ-forming hydrogels with growth factors and cells appear to be a promising approach in tissue engineering. To examine osteogenic differentiation of hTMSCs which is one of mesenchymal stem cells in vivo in an injectable hydrogel, we use a methoxy polyethylene glycol-polycaprolactone blockcopolymer (MPEG-PCL) solution with osteogenic factors. We synthesized MPEG-PCL hydrogel and measured viscosity to check sol-gel transition. In order to demonstrate osteogenic ability of hTMSCs, we conducted in vitro osteogenesis experiment. Then, to confirm the cell cytotoxicity, we performed WST-1 with hTMSCs and MPEG-PCL. As the result of in vitro experiment, we implanted cell and hydrogel mixture into animal model and checked degree of osteogenesis with histological analysis and amount of expression genes. Through these experimental data, MPEG-PCL hydrogel has sol-gel transition in temperature change and is biocompatible with stem cells. In histological analysis and gene expression, hTMSCs are very good source of osteogenesis with hydrogel and will use it to tissue engineering as important treatment method. hTMSCs could be a good adult stem cell source for usability of isolation and high proliferation. When hTMSCs are used as cell therapy method with in situ-formed hydrogel, they may provide various benefits like a noninvasive alternative for bone tissue engineering applications.

Keywords: injectable hydrogel, stem cell, osteogenic differentiation, tissue engineering

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4173 Development and Utilization of Keratin-Fibrin-Gelatin Composite Films as Potential Material for Skin Tissue Engineering Application

Authors: Sivakumar Singaravelu, Giriprasath Ramanathan, M. D. Raja, Uma Tirichurapalli Sivagnanam

Abstract:

The goal of the present study was to develop and evaluate composite film for tissue engineering application. The keratin was extracted from bovine horn and used for preparation of keratin (HK), physiologically clotted fibrin (PCF) and gelatin (G) blend films in different stoichiometric ratios (1:1:1, 1:1:2 and 1:1:3) by using solvent casting method. The composite films (HK-PCF-G) were characterized physiochemically using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and Scanning Electron Microscopy (SEM). The mechanical properties of the composite films were analyzed. The results of tensile strength show that ultimate strength and elongation were 10.72 Mpa and 4.83 MPA respectively for 1:1:3 ratio combination. The SEM image showed a slight smooth surface for 1:1:3 ratio combination compared to other films. In order to impart antibacterial activities, the composite films were loaded with Mupirocin (MP) to act against infection. The composite films acted as a suitable carrier to protect and release the drug in a controlled manner. This developed composite film would be a suitable alternative material for tissue engineering application.

Keywords: bovine horn, keratin, fibrin, gelatin, tensile strength

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4172 Self-Inflating Soft Tissue Expander Outcome for Alveolar Ridge Augmentation a Randomized Controlled Clinical and Histological Study

Authors: Alaa T. Ali, Nevine H. Kheir El Din, Ehab S. Abdelhamid, Ahmed E. Amr

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Objective: Severe alveolar bone resorption is usually associated with a deficient amount of soft tissues. soft tissue expansion is introduced to provide an adequate amount of soft tissue over the grafted area. This study aimed to assess the efficacy of sub-periosteal self-inflating osmotic tissue expanders used as preparatory surgery before horizontal alveolar ridge augmentation using autogenous onlay block bone graft. Methods: A prospective randomized controlled clinical trial was performed. Sixteen partially edentulous patients demanding horizontal bone augmentation in the anterior maxilla were randomly assigned to horizontal ridge augmentation with autogenous bone block grafts harvested from the mandibular symphysis. For the test group, soft tissue expanders were placed sub-periosteally before horizontal ridge augmentation. Impressions were taken before and after STE, and the cast models were optically scanned and superimposed to be used for volumetric analysis. Horizontal ridge augmentation was carried out after STE completion. For the control group, a periosteal releasing incision was performed during bone augmentation procedures. Implants were placed in both groups at re-entry surgery after six months period. A core biopsy was taken. Histomorphometric assessment for newly formed bone surface area, mature collagen area fraction, the osteoblasts count, and blood vessel count were performed. The change in alveolar ridge width was evaluated through bone caliper and CBCT. Results: Soft tissue expander successfully provides a Surplus amount of soft tissues in 5 out of 8 patients in the test group. Complications during the expansion period were perforation through oral mucosa occurred in two patients. Infection occurred in one patient. The mean soft tissue volume gain was 393.9 ± 322mm. After 6 months. The mean horizontal bone gains for the test and control groups were 3.14 mm and 3.69 mm, respectively. Conclusion: STE with a sub-periosteal approach is an applicable method to achieve an additional soft tissue and to reduce bone block graft exposure and wound dehiscence.

Keywords: soft tissue expander, ridge augmentation, block graft, symphysis bone block

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4171 Simulation of X-Ray Tissue Contrast and Dose Optimisation in Radiological Physics to Improve Medical Imaging Students’ Skills

Authors: Peter J. Riley

Abstract:

Medical Imaging students must understand the roles of Photo-electric Absorption (PE) and Compton Scatter (CS) interactions in patients to enable optimal X-ray imaging in clinical practice. A simulator has been developed that shows relative interaction probabilities, color bars for patient dose from PE, % penetration to the detector, and obscuring CS as Peak Kilovoltage (kVp) changes. Additionally, an anthropomorphic chest X-ray image shows the relative tissue contrasts and overlying CS-fog at that kVp, which determine the detectability of a lesion in the image. A series of interactive exercises with MCQs evaluate the student's understanding; the simulation has improved student perception of the need to acquire "sufficient" rather than maximal contrast to enable patient dose reduction at higher kVp.

Keywords: patient dose optimization, radiological physics, simulation, tissue contrast

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4170 In Situ Volume Imaging of Cleared Mice Seminiferous Tubules Opens New Window to Study Spermatogenic Process in 3D

Authors: Lukas Ded

Abstract:

Studying the tissue structure and histogenesis in the natural, 3D context is challenging but highly beneficial process. Contrary to classical approach of the physical tissue sectioning and subsequent imaging, it enables to study the relationships of individual cellular and histological structures in their native context. Recent developments in the tissue clearing approaches and microscopic volume imaging/data processing enable the application of these methods also in the areas of developmental and reproductive biology. Here, using the CLARITY tissue procedure and 3D confocal volume imaging we optimized the protocol for clearing, staining and imaging of the mice seminiferous tubules isolated from the testes without cardiac perfusion procedure. Our approach enables the high magnification and fine resolution axial imaging of the whole diameter of the seminiferous tubules with possible unlimited lateral length imaging. Hence, the large continuous pieces of the seminiferous tubule can be scanned and digitally reconstructed for the study of the single tubule seminiferous stages using nuclear dyes. Furthermore, the application of the antibodies and various molecular dyes can be used for molecular labeling of individual cellular and subcellular structures and resulting 3D images can highly increase our understanding of the spatiotemporal aspects of the seminiferous tubules development and sperm ultrastructure formation. Finally, our newly developed algorithms for 3D data processing enable the massive parallel processing of the large amount of individual cell and tissue fluorescent signatures and building the robust spermatogenic models under physiological and pathological conditions.

Keywords: CLARITY, spermatogenesis, testis, tissue clearing, volume imaging

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4169 Non-Invasive Imaging of Tissue Using Near Infrared Radiations

Authors: Ashwani Kumar Aggarwal

Abstract:

NIR Light is non-ionizing and can pass easily through living tissues such as breast without any harmful effects. Therefore, use of NIR light for imaging the biological tissue and to quantify its optical properties is a good choice over other invasive methods. Optical tomography involves two steps. One is the forward problem and the other is the reconstruction problem. The forward problem consists of finding the measurements of transmitted light through the tissue from source to detector, given the spatial distribution of absorption and scattering properties. The second step is the reconstruction problem. In X-ray tomography, there is standard method for reconstruction called filtered back projection method or the algebraic reconstruction methods. But this method cannot be applied as such, in optical tomography due to highly scattering nature of biological tissue. A hybrid algorithm for reconstruction has been implemented in this work which takes into account the highly scattered path taken by photons while back projecting the forward data obtained during Monte Carlo simulation. The reconstructed image suffers from blurring due to point spread function. This blurred reconstructed image has been enhanced using a digital filter which is optimal in mean square sense.

Keywords: least-squares optimization, filtering, tomography, laser interaction, light scattering

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4168 Durable Phantom Production Identical to Breast Tissue for Use in Breast Cancer Detection Research Studies

Authors: Hayrettin Eroglu, Adem Kara

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Recently there has been significant attention given to imaging of the biological tissues via microwave imaging techniques. In this study, a phantom for the test and calibration of Microwave imaging used in detecting unhealthy breast structure or tumors was produced by using sol gel method. The liquid and gel phantoms being used nowadays are not durable due to evaporation and their organic ingredients, hence a new design was proposed. This phantom was fabricated from materials that were widely available (water, salt, gelatin, and glycerol) and was easy to make. This phantom was aimed to be better from the ones already proposed in the literature in terms of its durability and stability. S Parameters of phantom was measured with 1-18 GHz Probe Kit and permittivity was calculated via Debye method in “85070” commercial software. One, three, and five-week measurements were taken for this phantom. Finally, it was verified that measurement results were very close to the real biological tissue measurement results.

Keywords: phantom, breast tissue, cancer, microwave imaging

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4167 Mercury and Selenium Levels in Swordfish (Xiphias gladius) Fished in the Exclusive Economic Zone of the Republic of Seychelles

Authors: Stephanie Hollanda, Nathalie Bodin, Carine Churlaud, Paco Bustamante

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Total mercury (Hg), selenium (Se) and Hg-Se ratios were analyzed in the white muscle, liver and gonads of swordfish, in order to compare concentration between the different tissues and sex, and also the effect of size (fork length). The results show significant difference between tissue types, with the liver having the highest concentration of both Hg and Se. Positive significant correlations between moles of Hg and Se were obtained in the liver and white muscle, but no relationship was obtained in the gonads. No difference in the concentration of Hg and Se was obtained between the sexes in the tissue types, except for Hg in the gonads, which were found to be higher in males. Significant negative relationships were obtained when the Hg-Se ratio was plotted against fork length in all three tissue types.

Keywords: bioaccumulation, large pelagic fish, mercury, selenium, western Indian Ocean

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4166 Development of 3D Printed Natural Fiber Reinforced Composite Scaffolds for Maxillofacial Reconstruction

Authors: Sri Sai Ramya Bojedla, Falguni Pati

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Nature provides the best of solutions to humans. One such incredible gift to regenerative medicine is silk. The literature has publicized a long appreciation for silk owing to its incredible physical and biological assets. Its bioactive nature, unique mechanical strength, and processing flexibility make us curious to explore further to apply it in the clinics for the welfare of mankind. In this study, Antheraea mylitta and Bombyx mori silk fibroin microfibers are developed by two economical and straightforward steps via degumming and hydrolysis for the first time, and a bioactive composite is manufactured by mixing silk fibroin microfibers at various concentrations with polycaprolactone (PCL), a biocompatible, aliphatic semi-crystalline synthetic polymer. Reconstructive surgery in any part of the body except for the maxillofacial region deals with replacing its function. But answering both the aesthetics and function is of utmost importance when it comes to facial reconstruction as it plays a critical role in the psychological and social well-being of the patient. The main concern in developing adequate bone graft substitutes or a scaffold is the noteworthy variation in each patient's bone anatomy. Additionally, the anatomical shape and size will vary based on the type of defect. The advent of additive manufacturing (AM) or 3D printing techniques to bone tissue engineering has facilitated overcoming many of the restraints of conventional fabrication techniques. The acquired patient's CT data is converted into a stereolithographic (STL)-file which is further utilized by the 3D printer to create a 3D scaffold structure in an interconnected layer-by-layer fashion. This study aims to address the limitations of currently available materials and fabrication technologies and develop a customized biomaterial implant via 3D printing technology to reconstruct complex form, function, and aesthetics of the facial anatomy. These composite scaffolds underwent structural and mechanical characterization. Atomic force microscopic (AFM) and field emission scanning electron microscopic (FESEM) images showed the uniform dispersion of the silk fibroin microfibers in the PCL matrix. With the addition of silk, there is improvement in the compressive strength of the hybrid scaffolds. The scaffolds with Antheraea mylitta silk revealed higher compressive modulus than that of Bombyx mori silk. The above results of PCL-silk scaffolds strongly recommend their utilization in bone regenerative applications. Successful completion of this research will provide a great weapon in the maxillofacial reconstructive armamentarium.

Keywords: compressive modulus, 3d printing, maxillofacial reconstruction, natural fiber reinforced composites, silk fibroin microfibers

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4165 Sterilization Effects of Low Concentration of Hydrogen Peroxide Solution on 3D Printed Biodegradable Polyurethane Nanocomposite Scaffold for Heart Valve Regeneration

Authors: S. E. Mohmad-Saberi, W. Song, N. Oliver, M. Adrian, T.C. Hsu, A. Darbyshire

Abstract:

Biodegradable polyurethane (PU) has emerged as a potential material to promote repair and regeneration of damaged/diseased tissues in heart valve regeneration due to its excellent biomechanical profile. Understanding the effects of sterilization on their properties is vital since they are more sensitive and more critical of porous structures compared to bulk ones. In this study, the effects of low concentration of hydrogen peroxide (H₂O₂) solution sterilization has been investigated to determine whether the procedure would be efficient and non-destructive to porous three-dimensional (3D) elastomeric nanocomposite, polyhedral oligomeric silsesquioxane-terminated poly (ethylene-diethylene glycol succinate-sebacate) urea-urethane (POSS-EDSS-PU) scaffold. All the samples were tested for sterility following sterilization using phosphate buffer saline (PBS) as control and 5 % v/v H₂O₂ solution. The samples were incubated in tryptic soy broth for the cultivation of microorganisms under agitation at 37˚C for 72 hours. The effects of the 5 % v/v H₂O₂ solution sterilization were evaluated in terms of morphology, chemical and mechanical properties using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) and tensile tester apparatus. Toxicity effects of the 5 % v/v H₂O₂ solution decontamination were studied by in vitro cytotoxicity test, where the cellular responses of human dermal fibroblast (HDF) were examined. A clear, uncontaminated broth using 5 % v/v H₂O₂ solution method indicated efficient sterilization after 3 days, while the non-sterilized control shows clouding broth indicated contamination. The morphology of 3D POSS-EDSS-PU scaffold appeared to have similar morphology after sterilization with 5 % v/v H₂O₂ solution regarding of pore size and surface. FTIR results show that the sterilized samples and non-sterilized control share the same spectra pattern, confirming no significant alterations over the surface chemistry. For the mechanical properties of the H₂O₂ solution-treated scaffolds, the tensile strain was not significantly decreased, however, become significantly stiffer after the sterilization. No cytotoxic effects were observed after the 5 % v/v H₂O₂ solution sterilization as confirmed by cell viability assessed by Alamar Blue assay. The results suggest that low concentration of 5 % v/v hydrogen peroxide solution can be used as an alternative method for sterilizing biodegradable 3D porous scaffold with micro/nano-architecture without structural deformation. This study provides the understanding of the sterilization effects on biomechanical profile and cell proliferation of 3D POSS-EDSS-PU scaffolds.

Keywords: biodegradable, hydrogen peroxide solution, POSS-EDSS-PU, sterilization

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4164 Classification System for Soft Tissue Injuries of Face: Bringing Objectiveness to Injury Severity

Authors: Garg Ramneesh, Uppal Sanjeev, Mittal Rajinder, Shah Sheerin, Jain Vikas, Singla Bhupinder

Abstract:

Introduction: Despite advances in trauma care, a classification system for soft tissue injuries of the face still needs to be objectively defined. Aim: To develop a classification system for soft tissue injuries of the face; that is objective, easy to remember, reproducible, universally applicable, aids in surgical management and helps to develop a structured data that can be used for future use. Material and Methods: This classification system includes those patients that need surgical management of facial injuries. Associated underlying bony fractures have been intentionally excluded. Depending upon the severity of soft tissue injury, these can be graded from 0 to IV (O-Abrasions, I-lacerations, II-Avulsion injuries with no skin loss, III-Avulsion injuries with skin loss that would need graft or flap cover, and IV-complex injuries). Anatomically, the face has been divided into three zones (Zone 1/2/3), as per aesthetic subunits. Zone 1e stands for injury of eyebrows; Zones 2 a/b/c stand for nose, upper eyelid and lower eyelid respectively; Zones 3 a/b/c stand for upper lip, lower lip and cheek respectively. Suffices R and L stand for right or left involved side, B for presence of foreign body like glass or pellets, C for extensive contamination and D for depth which can be graded as D 1/2/3 if depth is still fat, muscle or bone respectively. I is for damage to facial nerve or parotid duct. Results and conclusions: This classification system is easy to remember, clinically applicable and would help in standardization of surgical management of soft tissue injuries of face. Certain inherent limitations of this classification system are inability to classify sutured wounds, hematomas and injuries along or against Langer’s lines.

Keywords: soft tissue injuries, face, avulsion, classification

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4163 Nanowire Substrate to Control Differentiation of Mesenchymal Stem Cells

Authors: Ainur Sharip, Jose E. Perez, Nouf Alsharif, Aldo I. M. Bandeas, Enzo D. Fabrizio, Timothy Ravasi, Jasmeen S. Merzaban, Jürgen Kosel

Abstract:

Bone marrow-derived human mesenchymal stem cells (MSCs) are attractive candidates for tissue engineering and regenerative medicine, due to their ability to differentiate into osteoblasts, chondrocytes or adipocytes. Differentiation is influenced by biochemical and biophysical stimuli provided by the microenvironment of the cell. Thus, altering the mechanical characteristics of a cell culture scaffold can directly influence a cell’s microenvironment and lead to stem cell differentiation. Mesenchymal stem cells were cultured on densely packed, vertically aligned magnetic iron nanowires (NWs) and the effect of NWs on the cell cytoskeleton rearrangement and differentiation were studied. An electrochemical deposition method was employed to fabricate NWs into nanoporous alumina templates, followed by a partial release to reveal the NW array. This created a cell growth substrate with free-standing NWs. The Fe NWs possessed a length of 2-3 µm, with each NW having a diameter of 33 nm on average. Mechanical stimuli generated by the physical movement of these iron NWs, in response to a magnetic field, can stimulate osteogenic differentiation. Induction of osteogenesis was estimated using an osteogenic marker, osteopontin, and a reduction of stem cell markers, CD73 and CD105. MSCs were grown on the NWs, and fluorescent microscopy was employed to monitor the expression of markers. A magnetic field with an intensity of 250 mT and a frequency of 0.1 Hz was applied for 12 hours/day over a period of one week and two weeks. The magnetically activated substrate enhanced the osteogenic differentiation of the MSCs compared to the culture conditions without magnetic field. Quantification of the osteopontin signal revealed approximately a seven-fold increase in the expression of this protein after two weeks of culture. Immunostaining staining against CD73 and CD105 revealed the expression of antibodies at the earlier time point (two days) and a considerable reduction after one-week exposure to a magnetic field. Overall, these results demonstrate the application of a magnetic NW substrate in stimulating the osteogenic differentiation of MSCs. This method significantly decreases the time needed to induce osteogenic differentiation compared to commercial biochemical methods, such as osteogenic differentiation kits, that usually require more than two weeks. Contact-free stimulation of MSC differentiation using a magnetic field has potential uses in tissue engineering, regenerative medicine, and bone formation therapies.

Keywords: cell substrate, magnetic nanowire, mesenchymal stem cell, stem cell differentiation

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4162 Operating Characteristics of Point-of-Care Ultrasound in Identifying Skin and Soft Tissue Abscesses in the Emergency Department

Authors: Sathyaseelan Subramaniam, Jacqueline Bober, Jennifer Chao, Shahriar Zehtabchi

Abstract:

Background: Emergency physicians frequently evaluate skin and soft tissue infections in order to differentiate abscess from cellulitis. This helps determine which patients will benefit from incision and drainage. Our objective was to determine the operating characteristics of point-of-care ultrasound (POCUS) compared to clinical examination in identifying abscesses in emergency department (ED) patients with features of skin and soft tissue infections. Methods: We performed a comprehensive search in the following databases: Medline, Web of Science, EMBASE, CINAHL and Cochrane Library. Trials were included if they compared the operating characteristics of POCUS with clinical examination in identifying skin and soft tissue abscesses. Trials that included patients with oropharyngeal abscesses or that requiring abscess drainage in the operating room were excluded. The presence of an abscess was determined by pus drainage. No pus seen on incision or resolution of symptoms without pus drainage at follow up, determined the absence of an abscess. Quality of included trials was assessed using GRADE criteria. Operating characteristics of POCUS are reported as sensitivity, specificity, positive likelihood (LR+) and negative likelihood (LR-) ratios and the respective 95% confidence intervals (CI). Summary measures were calculated by generating a hierarchical summary receiver operating characteristic model (HSROC). Results: Out of 3203 references identified, 5 observational studies with 615 patients in aggregate were included (2 adults and 3 pediatrics). We rated the quality of 3 trials as low and 2 as very low. The operating characteristics of POCUS and clinical examination in identifying soft tissue abscesses are presented in the table. The HSROC for POCUS revealed a sensitivity of 96% (95% CI = 89-98%), specificity of 79% (95% CI = 71-86), LR+ of 4.6 (95% CI = 3.2-6.8), and LR- of 0.06 (95% CI = 0.02-0.2). Conclusion: Existing evidence indicates that POCUS is useful in identifying abscesses in ED patients with skin or soft tissue infections.

Keywords: abscess, point-of-care ultrasound, pocus, skin and soft tissue infection

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4161 Effect of Colloid Versus Crystalloid Administration in Cardiopulmonary Bypass Prime Solution on Tissue and Organ Perfusionm

Authors: Mohammad Java Esmaeily

Abstract:

Background: We evaluate the effects of tissue and organ perfusion during and after coronary artery bypass graft surgery with either colloid (Voluven) or crystalloid (Lactated ringers) as a prime solution. Materials and Methods: In this prospective randomized-controlled trial study, 70 patients undergoing on-pump coronary artery bypass graft surgery were randomly assigned to receive either colloid (Voluven) or crystalloid (Lactated ringer's) as a prime solution for initiation of cardiopulmonary bypass machine procedure. Tissue and organ perfusion markers, including lactate, troponin I, liver and renal function tests and electrolytes, were measured sequentially before induction (T1) to the second days after surgery (T5). Results: With the exception of chloride and potassium levels, no significant differences were detected in other measurements, and laboratory results were identical entirely in the two groups. Conclusion: Voluven® (hydroxyethyl starch, HES 130/0.4) has a not significant difference in comparison with crystalloid (Lactated ringer's) as priming solution on the basis of organ and tissue perfusion tests assessment.

Keywords: prime, colloid, crystalloid, lactate, troponin, hydroxyethyl starch

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4160 Association of Mir-196a Expression in Esophageal Tissue with Barrett´s Esophagus and Esophageal Adenocarcinoma

Authors: Petra Borilova Linhartova, Michaela Ruckova, Sabina Sevcikova, Natalie Mlcuchova, Jan Bohm, Katerina Zukalova, Monika Vlachova, Jiri Dolina, Lumir Kunovsky, Radek Kroupa, Zdenek Pavlovsky, Zdenek Danek, Tereza Deissova, Lydie Izakovicova Holla, Ondrej Slaby, Zdenek Kala

Abstract:

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. Specific microRNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, were repeatedly proved to play key roles in the pathogenesis of these diseases. This pilot study aimed to analyze four selected miRNAs in esophageal tissues from healthy controls (HC) and patients with reflux esophagitis (RE)/BE/EAC, as well as to compare expression at the site of Barrett's mucosa/adenocarcinoma and healthy esophageal tissue outside the area of the main pathology in patients with BE/EAC. In this pilot study, 22 individuals (3 HC, 8 RE, 5 BE, 6 EAC) were included and endoscopically examined. RNA was isolated from the fresh-frozen esophageal tissue (stored in the RNAlater™ Stabilization Solution −70°C) using the AllPrep DNA/RNA/miRNA Universal Kit. Subsequent RT-qPCR analysis was performed using selected TaqMan MicroRNA Assays for miR-21, miR-34a, miR-196a, miR-196b, and endogenous control (RNU44). While the expression of miR-21 in the esophageal tissue with the main pathology was decreased in BE and EAC patients in comparison to the group of HC and RE patients (p=0.01), the expression of miR-196a was increased in the BE and EAC patients (p<0.01). Correlations between those miRNAs expression in tissue and severity of diagnosis were observed (p<0.05). In addition, miR-196a was significantly more expressed at the site with the main pathology than in paired adjacent esophageal tissue in BE and EAC patients (p<0.01). In conclusion, our pilot results showed that miR-196a, which regulates the proliferation, invasion, and migration (and was previously associated with esophageal squamous cell carcinoma and marked as a potential therapeutic target), could be a diagnostic tissue biomarker for BE and EAC as well.

Keywords: microRNA, barrett´s esophagus, esophageal adenocarcinoma, biomarker

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4159 Personalized Tissues and Organs Replacement – a Peek into the Future

Authors: Asaf Toker

Abstract:

Matricelf developed a technology that enables the production of autologous engineered tissue composed of matrix and cells derived from patients Omentum biopsy. The platform showed remarkable pre-clinical results for several medical conditions. The company recently licensed the technology that enabled scientist at Tel Aviv university that 3D printed a human heart from human cells and matrix for the first time in human history. The company plans to conduct its first human clinical trial for Acute Spinal Cord Injury (SCI) early in 2023.

Keywords: tissue engineering, regenerative medicine, spinal Cord Injury, autologous implants, iPSC

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4158 Electro-Thermal Imaging of Breast Phantom: An Experimental Study

Authors: H. Feza Carlak, N. G. Gencer

Abstract:

To increase the temperature contrast in thermal images, the characteristics of the electrical conductivity and thermal imaging modalities can be combined. In this experimental study, it is objected to observe whether the temperature contrast created by the tumor tissue can be improved just due to the current application within medical safety limits. Various thermal breast phantoms are developed to simulate the female breast tissue. In vitro experiments are implemented using a thermal infrared camera in a controlled manner. Since experiments are implemented in vitro, there is no metabolic heat generation and blood perfusion. Only the effects and results of the electrical stimulation are investigated. Experimental study is implemented with two-dimensional models. Temperature contrasts due to the tumor tissues are obtained. Cancerous tissue is determined using the difference and ratio of healthy and tumor images. 1 cm diameter single tumor tissue causes almost 40 °mC temperature contrast on the thermal-breast phantom. Electrode artifacts are reduced by taking the difference and ratio of background (healthy) and tumor images. Ratio of healthy and tumor images show that temperature contrast is increased by the current application.

Keywords: medical diagnostic imaging, breast phantom, active thermography, breast cancer detection

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4157 The Effect of Vibration Amplitude on Tissue Temperature and Lesion Size When Using a Vibrating Cardiac Catheter

Authors: Kaihong Yu, Tetsui Yamashita, Shigeaki Shingyochi, Kazuo Matsumoto, Makoto Ohta

Abstract:

During cardiac ablation, high power delivery for deeper lesion formation is limited by electrode-tissue interface overheating which can cause serious complications such as thrombus. To prevent this overheating, temperature control and open irrigation are often used. In temperature control, radiofrequency generator is adjusted to deliver the maximum output power, which maintains the electrode temperature at a target temperature (commonly 55°C or 60°C). Then the electrode-tissue interface temperature is also limited. The electrode temperature is a result of heating from the contacted tissue and cooling from the surrounding blood. Because the cooling from blood is decreased under conditions of low blood flow, the generator needs to decrease the output power. Thus, temperature control cannot deliver high power under conditions of low blood flow. In open irrigation, saline in room temperature is flushed through the holes arranged in the electrode. The electrode-tissue interface is cooled by the sufficient environmental cooling. And high power delivery can also be done under conditions of low blood flow. However, a large amount of saline infusions (approximately 1500 ml) during irrigation can cause other serious complication. When open irrigation cannot be used under conditions of low blood flow, a new overheating prevention may be required. The authors have proposed a new electrode cooling method by making the catheter vibrating. The previous work has introduced that the vibration can make a cooling effect on electrode, which may result form that the vibration could increase the flow velocity around the catheter. The previous work has also proved that increasing vibration frequency can increase the cooling by vibration. However, the effect of the vibration amplitude is still unknown. Thus, the present study investigated the effect of vibration amplitude on tissue temperature and lesion size. An agar phantom model was used as a tissue-equivalent material for measuring tissue temperature. Thermocouples were inserted into the agar to measure the internal temperature. Porcine myocardium was used for lesion size measurement. A normal ablation catheter was set perpendicular to the tissue (agar or porcine myocardium) with 10 gf contact force in 37°C saline without flow. Vibration amplitude of ± 0.5, ± 0.75, and ± 1.0 mm with a constant frequency (31 Hz or 63) was used. A temperature control protocol (45°C for agar phantom, 60°C for porcine myocardium) was used for the radiofrequency applications. The larger amplitude shows the larger lesion sizes. And the higher tissue temperatures in agar phantom are also shown with the higher amplitude. With a same frequency, the larger amplitude has the higher vibrating speed. And the higher vibrating speed will increase the flow velocity around the electrode more, which leads to a larger electrode temperature decrease. To maintain the electrode at the target temperature, ablator has to increase the output power. With the higher output power in the same duration, the released energy also increases. Consequently, the tissue temperature will be increased and lead to larger lesion sizes.

Keywords: cardiac ablation, electrode cooling, lesion size, tissue temperature

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4156 Numerical Simulation of Heating Characteristics in a Microwave T-Prong Antenna for Cancer Therapy

Authors: M. Chaichanyut, S. Tungjitkusolmun

Abstract:

This research is presented with microwave (MW) ablation by using the T-Prong monopole antennas. In the study, three-dimensional (3D) finite-element methods (FEM) were utilized to analyse: the tissue heat flux, temperature distributions (heating pattern) and volume destruction during MW ablation in liver cancer tissue. The configurations of T-Prong monopole antennas were considered: Three T-prong antenna, Expand T-Prong antenna and Arrow T-Prong antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The microwave power deliveries were 10 W; the duration of ablation in all cases was 300s. Our numerical result, heat flux and the hotspot occurred at the tip of the T-prong antenna for all cases. The temperature distribution pattern of all antennas was teardrop. The Arrow T-Prong antenna can induce the highest temperature within cancer tissue. The microwave ablation was successful when the region where the temperatures exceed 50°C (i.e. complete destruction). The Expand T-Prong antenna could complete destruction the liver cancer tissue was maximized (6.05 cm³). The ablation pattern or axial ratio (Widest/length) of Expand T-Prong antenna and Arrow T-Prong antenna was 1, but the axial ratio of Three T-prong antenna of about 1.15.

Keywords: liver cancer, T-Prong antenna, finite element, microwave ablation

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4155 DOG1 Expression Is in Common Human Tumors: A Tissue Microarray Study on More than 15,000 Tissue Samples

Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

Abstract:

DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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