SM Journal of Biomedical Engineering

Archive Articles

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The Effect of WIN55, 212-2 on Protein S100, Matrix Metalloproteinase-2 and Nitric Oxide Expression of Chondrocyte Monolayer

Studies have been conducted to highlight the anti-inflammatory and immunosuppressive properties of synthetic cannabinoids as well as their potential for cartilage repair. Various wound healing techniques can be used to investigate the mechanisms of chondrocyte repair in monolayers or three dimensional tissues constructs. In this work the effect of WIN55, 212-2 (WIN-2) on nitric oxide (NO) and matrix metalloproteinase-2 (MMP-2) expressed by wounded chondrocyte monolayers was investigated. Moreover, expression of collagen type-I and type-II, fibronectin and S100 proteins were detected using immunofluorescence and quantitatively verified using ELISA based techniques following treatment with 1 µM and 2 µM of WIN-2. Treating chondrocytes with 1 µM of WIN-2 significantly increased expression of collagen type-II, fibronectin and S100, and significantly reduced collagen type-I expressions as compared to the control groups. On the other hand, both concentrations of WIN-2 significantly reduced the expression of the inflammation markers NO and MMP-2 in a dose dependent manner. These findings highlight the potential use of the synthetic cannabinoids for improving cartilage healing properties as well as acting as an anti-inflammatory agent which could be used to enhance tissue engineering protocols aimed at cartilage repair.

A Abdeldayem¹, M Youseffi¹*, F Sefat¹, M Genedy¹, MM Abdul Jamil², and F Javid³


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Investigation of Rice as an Absorbent and Degradable Material for Personal Hygiene Applications

This research explores the uses of natural materials in personal hygiene applications. In order to maximize the use of materials for personal hygiene, they must be absorbent, but should also be biodegradable to minimize their impact on the environment. Rice was prepared for testing by increase the porosity. The material was ground into three size distributions and tested to determine its ability to absorb moisture under both ambient and body temperatures. Research goals address the percentage of moisture absorbed by weight, the absorption as a function of temperature, and the optimal particle size required for the selected application. Results indicate that the amount of moisture absorbed by the material increases as the temperature approaches body temperature. Furthermore, the time required for the material to reach equilibrium, as also defined by the amount at which the material will no longer absorb moisture, varies by particle size.

Jeffrey S Bates¹*, Megan A Adams¹, and Taylor D Sparks¹


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Automatic Segmentation of Glioma from 3D MR Images by Using Location Free Asymmetry Detection

Accurate segmentation of glioma from Magnetic Resonance (MR) imagery undoubtedly provides essential assistance for glioma resection and following progress evaluation after the resection. Numerous methods have been presented to segment glioma from Two Dimensional (2D) or Three Dimensional (3D) MR images. To deal with the complex structure of brain and the various shapes of glioma, methods based on selecting asymmetric areas with respect to the approximate symmetry of brain are widely used. This kind of methods, however, may fail in the case of segmenting the glioma across the mid-sagittal plane. This paper developed a fully 3D automatic asymmetry detection method for the glioma segmentation, while overcoming the location limitation in conventional asymmetry detection methods. The proposed 3D bounding box method locates glioma in the Voxel of Interest (VOI), which is checked and corrected by the reflectional method. With the accurate VOI, the improved 3D GrowCut method is employed to segment glioma automatically and quickly. We evaluated the accuracy of the proposed method by using both synthetic and real clinical MR image data. Experimental results show that our method conquers the difficulties of conventional asymmetry detection method when segmenting the glioma across the mid-sagittal plane successfully. Our method provides similar segmentation performance with manual segmentation and shows obvious higher efficiency and more convenience than 2D automatic segmentation method.

Guoqing Wu¹#, Chunhong Ji¹#, Jinhua Yu¹,²*, Yuanyuan Wang¹, Liang Chen³, Zhifeng Shi³, and Ying Mao³


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The Typical Carbuncle Form of Cutaneous Anthrax

The two images below represent the carbuncle on the 15th day of disease (the 8th day of hospitalization) of the 48 year-old patient from Republic of Moldova that accidentally injured himself while slaughtering three sick lambs.

Bunescu I¹*, Holban T¹, Robiș S², Musteață T³, Moraru L³, Potîng-Rașcov V¹, Semeniuc S¹, Bîstrițchi I¹, Cojocaru S¹, Rusu I¹, and Dubineanschi N¹


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Organ Movement and Targeting during Non-Invasive Therapy and Surgery

One of the major challenges faced during non-invasive treatment and surgery of tumours or cancers in abdominal organs such as the liver, lungs or kidneys is the continuous movement due to physiological processes. This motion creates the need for comprehensive treatment planning in order to understand the target movement, compute the relative motion of the energy delivery system and compensate for the motion during image-guided robotic surgery. Without correct motion estimation, the target volume may suffer from inaccurate dosage delivery and/or adverse effects on the surrounding healthy tissue. A number of approaches have been proposed to deal with motion tracking. A succinct review of the methods used in the motion estimation and management of moving target volumes in the major abdominal organs, such as lungs, liver and kidney, are presented in this paper.

Mustafa A¹, Abhilash RH², and Chauhan S³*


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Multi-field Semi-Lagrangian Reproducing Kernel Particle Method for Landslide Simulation

This paper presents a multi-field meshfree method based on a semi-Lagrangian reproducing kernel particle method for simulation of landslide processes. In the proposed method, the approximation functions of field variables are constructed based on particles, without the need of grids or structured mesh, and the discrete state variables follow the particles, thus Lagrangian description; while the interpolation function of each particle is continually updated during deformation. The formulation naturally handles extremely large deformation and material separation, thus the method is well-suited to capture the deformation of geomaterials transitioning from elastic to an almost fluid-like deformation mode during a landslide event. The general Biot theory is incorporated in the multi-field semi-Lagrangian formulation to describe the behaviors of porous geomaterials. Several numerical examples are presented for verification of the proposed method and a landslide simulation is validated against experimental results.

Thanakorn Siriaksorn¹ and Sheng-Wei Chi²*


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Effect of Frequency and Focal Depth of Push Pulses on Acoustic Intensity, Mechanical Index, and Shear Wave Amplitude for Elastography Imaging

Over the past few years, there has been an increase on the application of Shear Wave Elastography (SWE) techniques to measure mechanical properties of musculoskeletal tissues for clinical applications. Imaging soft musculoskeletal tissues often requires the use of high frequency probes for high resolution at lower depths. The objective of this study is to measure the effect of frequency and focal depth on the acoustic output parameters (ISPPA , ISPTA and MI) as well as the amplitude of the generated shear waves by a ‘push’ pulse. To do this, acoustic output parameters were measured following NEMA guidelines. The frequency range used for the push pulses was 5-10MHz. The effect of frequency and focal depth on the amplitude of shear waves was evaluated on ultrasound phantom as well as on muscle and Achilles tendon. Acoustic output parameters and shear wave amplitude decreased as function of focal depth. However, the maximum acoustical intensity and the maximum displacement occurred at different frequencies. The maximum acoustic intensity was found at the center frequency of the transducer. These results shed light into the relationships between the properties of the ultrasound probe, acoustic output parameters, and shear wave amplitude for elastography applications.

Seyedali Sadeghi¹, Sean Rothenberger¹, Dooman Akbarian¹, and Daniel H Cortes¹,²*


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Microfluidics for Single Cell Mechanical Characterization: A Review

Mechanical characterization of cells may be used to distinguish and to select certain types of cells and, more importantly, to discriminate between healthy and diseased cells. This means that mechanical properties of cells could be used as markers to screen and diagnose for diseases like cancer, malaria, and cardiovascular diseases, without the need for biochemical assaying. Conventional cell mechanical characterization methods are not suitable for practical clinical application since they are tedious and have a low throughput. Microfluidic technology holds great promise to realize single cell mechanical characterization devices that are suitable for clinical use. In recent years, many devices based on different microfluidic principles for characterizing cell mechanical properties have been introduced in the literature and science has developed up to a point at which the next steps must be taken to enable the actual translation into the clinic. In this paper, we review the different methods discussing advantages and disadvantages, and we conclude on the major challenges that need to be tackled next to enable the translation towards clinical application.

Ravetto A¹, Anderson PDA²,³, Bouten CVC¹,³, and den Toonder JMJ²,³*


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Radiation Induced Secondary Lung Cancer Detected with F-18 FDG-PET/ CT 20 Years after Radiotherapy of Breast Cancer

Irradiation of surrounding tissues during breast Radiotherapy (RT) may cause secondary cancers to develop within these tissues. Here we report a case of non-small cell lung cancer developed within irradiated field of right lung after RT of right breast cancer 20 years later which was detected with Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (F-18 FDG PET/CT).

Burcak Yilmaz Gunes¹* and Fatih Hikmet Özvar²


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Idiopathic Pulmonary Fibrosis Management Review

Idiopathic Pulmonary Fibrosis (IPF) is a progressive and often fatal disease that usually manifests with dyspnea, cough and/or fatigue. The diagnosis of IPF requires the exclusion of known causes of pulmonary f ibrosis. The diagnosis and management of patients with IPF ideally should be done in specialized interstitial lung disease centers in order to provide patients with the best possible care; this includes pharmacological and non-pharmacological therapeutic options to slow down the progression of the disease, to manage symptoms and to improve the quality of life of patients with IPF. The main treatment options include antifibrotic drugs, opioids, supplementary oxygen, pulmonary rehabilitation and lung transplantation. This review summarizes the guidelines and scientific evidence that support the various therapeutic options currently used in the management of patients with IPF. We also summarize the evidence on the therapeutic options for pulmonary hypertension and acute exacerbations of IPF, two complications associated with increased risk of death in IPF patients.

Alyami S¹, Yang R², and Moran-Mendoza O¹*


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A Study on Semi-Late Maize Hybrids for Resistance to Smut of Maize /Ustilago maydis/

The most efficient method of controlling diseases of economic importance in agricultural crops is breeding of resistant varieties.

The objective of the study was to determine the extent of the attack of smut of maize /Ustilago maydis/ on 22 hybrids and 4 maize standards under conditions, conducive to the spread of the pathogen. The study was conducted in the experimental fields of the Institute of Agriculture and Seed Science “Obraztsov Chiflik”, Ruse during the period 2012 - 2014. 26 germplasms of Preliminary Variety Trial N 2 (PVT) were included. Ustilago maydis is a common disease in most parts of the world, where maize is grown.

In all above-ground organs of the plant, tumors of smutty mass are formed. The pathogen attack leads to stunted growth of the host plant, reducing yield, and economic losses. The analysis of data about the new hybrids of IASS “Obraztsov Chiflik” - Ruse showed that fifteen of them were resistant. The resistance was the highest in the hybrids: St.20, Eks.12, Eks.10, Eks.23, Eks.16, Eks.2, Eks.3, Eks.4, Eks.6, Eks.9, Eks.13, Eks.17, Eks.19, Eks.20, 2 Eks.6. They may be used as sources of resistance. Susceptible were: Eks.15, Eks.11, Eks.8, Eks.24, Eks.1, Eks.5, St.7, Eks.14, Eks.18, Eks.22, Eks.25.

Iliana Ivanova¹*, Lyubomir Ivanov, and Gergana Ivanova


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The Effect of Clearance upon Friction of Large Diameter Hip Resurfacing Prostheses using Blood and Combinations of Bovine Serum with Aqueous Solutions of Cmc and Hyaluronic Acid as Lubricants

In real life, immediately after joint replacement, the artificial joint is actually bathed in blood instead of synovial fluid. Blood contains large molecules and cells of size ~ 5 to 20 micron suspended in plasma and considered to be a non-Newtonian (pseudoplastic) fluid with viscosity ~ 0.01 Pas at shear rates of 3000 s-1. The effect of these properties on friction is not fully understood and, so far, hardly any studies have been carried out regarding friction of metal-on-metal bearings with various clearances in the presence of lubricants such as blood or a fluid containing macromolecules such as Hyaluronic Acid (HA) which is a major component of synovial f luid, increasing its viscosity and lubricating properties. In this work, therefore, the frictional behaviour of a group of Smith and Nephew Birmingham Hip Resurfacing devices with a nominal diameter of 50mm and diametral clearances in the range ~ 80 to 300µm, in the presence of blood (clotted and whole blood), a combination of Bovine Serum (BS) with Hyaluronic Acid (HA) and Carboxymethyl Cellulose (CMC) adjusted to a range of viscosities (~0.001-0.2 Pas), and bovine serum with CMC adjusted to a similar range of viscosities have been investigated.

The results suggest that reduced clearance bearings have the potential to generate high friction especially in the presence of blood which is indeed the in vivo lubricant in the early weeks after implantation. Friction factors in higher clearance bearings were found to be lower than those of the lower clearance bearings using blood as the lubricant.

Mansour Youseffi¹*, Saeed Afshinjavid², and Farideh Javid³


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Hyperbaric Pressure Chamber Structural Integrity Testing for Vascular Access Ports

A total of 25 commercially available vascular access ports were evaluated in this study. Included were 5 different port models and n=5 ports per model. Port types were placed into separate water baths with respect to each model. Each was pressurized to 3 ATA (atmosphere absolute) in a hyperbaric pressure chamber simultaneously. Ports were investigated for escape gases in the water bath as well as for surface tension changes at the distal catheter end while under hyperbaric pressure. No escape gases or catheter surface tension changes were observable. The study concludes successful results for all ports in a hyperbaric chamber, when no f luid injection flow rate is necessary during pressurization.

Michael S Gossman¹* and Mark Brown²


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Quantitative Evaluation of 3D Printed Anatomical Objects: A Comparison of Optical Surface Scanning and Micro Computed Tomography

Additive manufacturing technologies are increasingly used for medical purposes. However, questions are regularly raised about the accuracy of the anatomical models thus obtained. The present study compares two investigative methods that are used for assessing the degree of trueness of 3D printed replicas and presents recommendations for future analyses. The two techniques compared are optical surface scanning by structured light (OSS) and micro-computed tomography (µCT). The comparison was made by investigating an original cranial vault and its replica obtained by selective laser sintering (Eosint P 385, EOS GmbH, Krailling, Germany). OSS tests were conducted using a kolibri Cordless scanner (Fraunhofer IOF, Jena, Germany); µCT was performed with a v?tome?x 240/180 machine (phoenix?x-ray, GE, Wunstorf, Germany). The degree of trueness of the replica was assessed with an iterative closest point algorithm (Geomagic Qualify software, Version 12, Geomagic GmbH, 3D Systems, Rock Hill, USA).The replica’s deviations from the original, measured by OSS and µCT, respectively, were as follows: Homogeneous enlargement factor: 1.3% vs 1.2%; Mean shape deviation: +0.27mm (±0.15mm) vs +0.24mm (±0.23mm); Shape deviation

Jean HD Fasel¹*, Anne-Sophie Knoepfli², Diego San Millan³, Roland Ramm⁴, and Peter Kühmstedt⁴


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Mechanisms of Action of an Intraarticular 2.5% Polyacrylamide Hydrogel (Arthramid Vet) in a Goat Model of Osteoarthritis: Preliminary Observations

A 2.5% Polyacrylamide Hydrogel (PAAG)a was tested for treatment of Osteoarthritis (OA) in a goat model (transection of medial collateral ligament, bisection of medial meniscus and partial-thickness cartilage incisions of medial tibial plateau) with highly encouraging results. The objective was to describe preliminary observations of the mechanisms of action of PAAG in OA joints, based on MRI, pathology and joint capsule elasticity investigations. A randomized controlled study was conducted on an OA knee model in goats: treatment group (intraarticular PAAG), control group (intraarticular saline). Magnetic Resonance Imaging (MRI) was performed prior to surgery, 3, 4, 5 and 7 months post-surgery. Seven months post-surgery, gross pathology and histopathology, including immunohistochemistry for nerve endings, were performed on both knees. Joint capsule elasticity of the knees was measured in both groups.

MRI showed reduction followed by stabilization of OA lesions after PAAG treatment. At gross pathology, PAAG was seen adhering to synovial membrane. Histopathology showed that intraarticular PAAG injection added to the thickness of the synovial membrane by allowing angiogenesis, collagen and synovial cell increase; PAAG was integrated into the synovial membrane. Nerve endings were intact with normal morphology and numbers. Joint capsule elasticity investigation showed that treated knees had a higher elasticity when compared to control knees. This study presents preliminary observations of the mechanisms of action of PAAG on OA joints: (1) Pathology and joint capsule elasticity suggest that PAAG by acting on synovial membrane may reduce overall joint capsule stiffness, a major source of pain in OA. (2) MRI and pathology revealed stabilization of OA lesions in PAAG treated goats, possibly caused by the high viscosupplementation of PAAG.

Aziz Tnibar¹*, Ann Britt Persson¹, and Henrik Elvang Jensen²


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Environmental Dioxin Pollution and its Influence on the African Americans

Dioxins are a group of chemically-related compounds that are persistent environmental pollutants and are formed as an unintentional by-product of many industrial processes involving chlorine such as waste incineration, chemical and pesticide manufacturing and pulp and paper bleaching. Some toxicity of other dioxins and chemicals like PCBs that act like dioxin are measured in relation to TCDD. However, dioxin is a general name for a large group of chemical compounds with similar structure. These compounds are made up of the number of the chlorine atoms and their positions in the dioxin molecule are what determine the toxicity of different dioxins. Dioxin is formed by burning chlorine-based chemical compounds with paper mills which use chlorine bleaching in their process and with the production of Polyvinyl Chloride (PVC) plastics and with the production of certain chlorinated chemicals. In September 1994, by the U.S, Environmental Protection Agency clearly describes dioxin as a serious public health threat. According to the EPA report, not only does there appear to be no “safe” level of exposure to dioxin, but levels of dioxin and dioxin-like chemicals have been found in the general U.S population that are at or near levels associated with adverse health effects. Dioxin was the primary toxic component of Agent Orange, which was found at Love Canal in Niagara Falls, NY and was the basis for evacuations at Times Beach, MO and Seveso, Italy. The most toxic compound is 2, 3, 7, 8 - Tetrachlorodibenzo - Para - Dioxin or TCDD.

Prabir K Mandal¹*, Aaliyah Tomkins, Anita Mandal, and Jakori Duffy


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Design and Development of a Novel Sitagliptin-Loaded Transdermal Patch for Diabetes Treatment

Sitagliptin is a dipeptidyl peptidase 4-(DPP-4) inhibitor with glucose controlling capabilities that was effectively used for treating diabetes in the past. However, the oral administration of this drug caused such severe side effects that it was removed from the market. In the present study, Sitagliptin was formulated in a gel-type reservoir on a transdermal patch device, optimized by a mathematical simulation methodology, and experimentally validated in vitro using a Franz Cell apparatus. The mathematical model determined optimal design parameters which included 1% w/w acellulose as drug reservoir, transdermal patch rate control membranes, 1.25 mM initial drug concentration, 2 mL initial volume, and 4.52 cm2 patch area. This optimized reservoir formulation was then fabricated in the transdermal patch system and tested using Franz Cell to validate the simulation. The experimental results from the fabricated transdermal patch system indicated that Sitagliptin can be formulated in a patch to achieve the target effective plasma drug concentration in less than one hour and is able to sustain glucose control for over 24 hours.

Daniel Griffin J, Sarah Colón, Deshawn Gray, Brenden Overton, and Bin Wang¹*


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Gravity, Mechanotransduction and Healing: How Mechanical Forces Promote Tissue Repair

Gravity plays a central role in vertebrate development, evolution and repair and regeneration responses. Recent studies suggest that tissue repair may in part be stimulated by mechanical loading of tissues in a process by which addition of mechanical energy leads to changes in tissue metabolism by mechanotransduction. In this paper we summarize reported research studies on how mechanotransduction can stimulate repair of tissues to enable clinicians to promote healing of chronic wounds and assist in the facilitation of production of tissue engineered products.

External energy in the form of extracorporeal shock waves, low intensity vibrations, pulsed electromagnetic waves and vacuum assisted wound healing have been used to promote healing. Results of research studies on cells and tissues suggest that mechanical loading can down-regulate inflammation, modify natural immune responses during healing and is also associated with promoting angiogenesis. Using vibrational OCT, a non destructive and non-invasive method to measure mechanical properties of tissues and implants, it is possible to evaluate the effects of mechanotransduction on repair responses. Further studies are needed to optimize the healing effects of mechanotransduction in bone, tendon, cartilage, nerve, myocardium, cardiovascular tissue, and skin.

Frederick H Silver¹* and Lisa L Silver²