Search results for: tissue repair

Authors: Andreia Cucuruz, Cristina Daniela Ghitulica, Georgeta Voicu, Cristina Busuioc

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Ceramics based on calcium phosphates have lately increased attention for tissue engineering because they can be used as substitute bones or for bone regeneration since they mimic very well the nanostructure of tough bone tissue, but also because of other advantages such as a very good biocompatibility and osseointegration. This study aims the preparation and characterization of ceramic materials on the basis of TCP (Ca₃(PO₄)₂), within which calcium ions are substituted by magnesium ions (Mg²⁺) in order to improve the regenerative properties of these materials. TCP-Mg material was synthesized by chemical precipitation method using calcium oxide (CaO) and phosphoric acid (H₃PO₄) as precursors. The objective was to obtain powders with different concentrations of Mg in order to analyze the effect of magnesium ions on the physicochemical properties of phosphate ceramics and in vitro degradation in simulated biological fluid (SBF). Ceramic powders were characterized in vitro but also from the compositional and microstructural point of view. TCP_Mg powders were prepared through wet chemical method from calcium oxide (CaO), magnesium oxide nanopowder (MgO < 50 nm particle size (BET) Sigma Aldrich), phosphoric acid (H₃PO₄ - 85 wt.% in H₂O, 99.99% trace metals basis - Sigma Aldrich). In order to determine the quantities of raw materials, calculations were performed to obtain HAp with Ca/P ratio of 1.5.

Keywords: bone regeneration, magnesium substitution, tricalcium phosphate, tissue engineering

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Authors: Mehrnaz Aminitabar, Moghan Amirhosseinian, Morteza Elsa

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Bioactive glasses (BGs) are a group of surface-reactive biomaterials used in clinical applications as implants or filler materials in the human body to repair and replace diseased or damaged bone. Sol-gel technique was employed to prepare a SiO₂-CaO-P₂O₅ glass with nominal composition of 58S BG with the addition of Sr and Li modifiers which imparts special properties to the BG. The effect of simultaneous addition of Sr and Li on bioactivity and biocompatibility, proliferation, alkaline phosphatase (ALP) activity of osteoblast cell line MC3T3-E1 and antibacterial property against methicillin-resistant Staphylococcus aureus (MRSA) bacteria were examined. BGs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy before and after soaking the samples in the simulated body fluid (SBF) for different time intervals to characterize the formation of hydroxyapatite (HA) formed on the surface of BGs. Structural characterization indicated that the simultaneous presence of 5% Sr and 5% Li in 58S-BG composition not only did not retard HA formation because of opposite effect of Sr and Li of the dissolution of BG in the SBF but also, stimulated the differentiation and proliferation of MC3T3-E1s. Moreover, the presence of Sr and Li on dissolution of the ions resulted in an increase in the mean number of DAPI-labeled nuclei which was in good agreement with live/dead assay. The result of antibacterial tests revealed that Sr and Li-substituted 58S BG exhibited a potential antibacterial effect against MRSA bacteria. Because of optimal proliferation and ALP activity of MC3T3-E1cells, proper bioactivity and high antibacterial potential against MRSA, BG-5/5 is suggested as a multifunctional candidate for bone tissue engineering.

Keywords: antibacterial activity, bioactive glass, sol-gel, strontium

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Authors: Sultan Z. Mahmud, Emily C. Graff, Adil Bashir

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Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional adapter protein which is associated with the regulation of apoptotic cell death. Recently it has been discovered that PEA-15 is crucial in normal neurodevelopment of domestic cats, a gyrencephalic animal model, although the exact function of PEA-15 in neurodevelopment is unknown. This study investigates how PEA-15 affects the blood-brain barrier (BBB) permeability in cat brain, which can cause abnormalities in tissue metabolite and energy supplies. Severe polymicrogyria and microcephaly have been observed in cats with a loss of function PEA-15 mutation, affecting the normal neurodevelopment of the cat. This suggests that the vital role of PEA-15 in neurodevelopment is associated with gyrification. Neurodevelopment is a highly energy demanding process. The mammalian brain depends on glucose as its main energy source. PEA-15 plays a very important role in glucose uptake and utilization by interacting with phospholipase D1 (PLD1). Mitochondria also plays a critical role in bioenergetics and essential to supply adequate energy needed for neurodevelopment. Cerebral blood flow regulates adequate metabolite supply and recent findings also showed that blood plasma contains mitochondria as well. So the BBB can play a very important role in regulating metabolite and energy supply in the brain. In this study the blood-brain permeability in cat brain was measured using MRI magnetization transfer (MT) effect on the perfusion signal. Perfusion is the tissue mass normalized supply of blood to the capillary bed. Perfusion also accommodates the supply of oxygen and other metabolites to the tissue. A fraction of the arterial blood can diffuse to the tissue, which depends on the BBB permeability. This fraction is known as water extraction fraction (EF). MT is a process of saturating the macromolecules, which has an effect on the blood that has been diffused into the tissue while having minimal effect on intravascular blood water that has not been exchanged with the tissue. Measurement of perfusion signal with and without MT enables to estimate the microvascular blood flow, EF and permeability surface area product (PS) in the brain. All the experiments were performed with Siemens 7T Magnetom with 32 channel head coil. Three control cats and three PEA-15 mutant cats were used for the study. Average EF in white and gray matter was 0.9±0.1 and 0.86±0.15 respectively, perfusion in white and gray matter was 85±15 mL/100g/min and 97±20 mL/100g/min respectively, PS in white and gray matter was 201±25 mL/100g/min and 225±35 mL/100g/min respectively for control cats. For PEA-15 mutant cats, average EF in white and gray matter was 0.81±0.15 and 0.77±0.2 respectively, perfusion in white and gray matter was 140±25 mL/100g/min and 165±18 mL/100g/min respectively, PS in white and gray matter was 240±30 mL/100g/min and 259±21 mL/100g/min respectively. This results show that BBB is compromised in PEA-15 mutant cat brain, where EF is decreased and perfusion as well as PS are increased in the mutant cats compared to the control cats. This findings might further explain the function of PEA-15 in neurodevelopment.

Keywords: BBB, cat brain, magnetization transfer, PEA-15

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Authors: P. Dey, S. K. Pal

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Ceramics or glass ceramics with the property of bone bonding at the nearby tissues and producing possible bone in growth are known to be bioactive. The most extensively used glass in this context is 45S5 which is a silica based bioglass mostly explored in the field of tissue engineering as scaffolds for bone repair. Nowadays, the borate based bioglass are being utilized in orthopedic area largely due to its superior bioactivity with the formation of bone bonding. An attempt has been made, in the present study, to observe the effect of B2O3 addition in 45S5 glass and perceive its consequences on the thermal, mechanical and biological properties. The B2O3 was added in 1, 2.5, and 5 wt% with simultaneous reduction in the silica content of the 45S5 composition. The borate based bioglass has been synthesized by the means of sol-gel route. The synthesized powders were then thermally analyzed by DSC-TG. The as synthesized powders were then calcined at 600ºC for 2hrs. The calcined powders were then pressed into pellets followed by sintering at 850ºC with a holding time of 2hrs. The phase analysis and the microstructural analysis of the as synthesized and calcined powder glass samples and the sintered glass samples were being carried out using XRD and FESEM respectively. The formation of hydroxyapatite layer was performed by immersing the sintered samples in the simulated body fluid (SBF) and mechanical property has been tested for the sintered samples by universal testing machine (UTM). The sintered samples showed the presence of sodium calcium silicate phase while the formation of hydroxyapaptite takes place for SBF immersed samples. The formation of hydroxyapatite is more pronounced in case of borated based glass samples instead of 45S5.

Keywords: 45S5 bioglass, bioactive, borate, hydroxyapatite, sol-gel synthesis

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Authors: Walid Ibrahim, Abdul Kasem, Sudeendra Doddi, Ilaria Giono, Tareq Sabagh, Muhammad Ammar, Nermin Osman

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Background: wire-guided localization (WL) is the most widely used method for the localization of non-palpable breast lesions. SAVI SCOUT occult lesion localization (SSL) is a new technique in breast-conservative surgery. SSL has the potential benefit of improving radiology workflow as well as accurate localization. Purpose: The purpose of this study is to compare the breast tissue specimen volume and weight and margin excision between WL and SSL. Materials and methods: A single institution retrospective analysis of 377 female patients who underwent wide local breast excision with SAVI SCOUT and or wire-guided technique between 2018 and 2021 in a UK University teaching hospital. Breast department. Breast tissue specimen volume and weight, and margin excision have been evaluated in the three groups of different localization. Results: Three hundred and seventy-seven patients were studied. Of these, 261 had wire localization, 88 had SCOUT and 28 had dual localization techniques. Tumor size ranged from 1 to 75mm (Median 20mm). The pathology specimen weight ranged from 1 to 466gm (Median 46.8) and the volume ranged from 1.305 to 1560cm³ (Median 106.32 cm³). SCOUT localization was associated with a significantly low specimen weight than wire or the dual technique localization (Median 41gm vs 47.3gm and 47gm, p = 0.029). SCOUT was not associated with better specimen volume with a borderline significance in comparison to wire and combined techniques (Median 108cm³ vs 105cm³ and 105cm³, p = 0.047). There was a significant correlation between tumor size and pathology specimen weight in the three groups. SCOUT showed a better >2mm safety margin in comparison to the other 2 techniques (p = 0.031). Conclusion: Preoperative SCOUT localization is associated with better specimen weight and better specimen margin. SCOUT did not show any benefits in terms of specimen volume which may be due to difficulty in getting the accurate specimen volume due to the irregularity of the soft tissue specimen.

Keywords: scout, wire, localization, breast

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Authors: Rossana Taravella, Gilberto M. Cellura, Giuseppe Cirrincione, Salvatore Asciutto, Marco Caruso, Massimo Benedetto, Renato Ciofalo, Giuliana Pace, Salvatore Novo

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Objectives: This retrospective analysis sought to evaluate 1-month outcomes and therapy effectiveness of a population of patients treated with MitraClip therapy. We describe in this article the preliminary results of primary effectiveness endpoint. Background: Percutaneous Mitral Repair is being developed to treat severe mitral regurgitation (MR), with increasing real-world cases of functional MR (FMR). In the EVEREST (Endovascular Valve Edge-to-Edge Repair Study)II trial, the percutaneous device showed superior safety but less reduction in MR at 1year. 4-year outcomes from EVEREST II trial showed no difference in the prevalence of moderate-severe and severe MR or mortality at 4years between surgical mitral repair and percutaneous approach. Methods: We analysed retrospectively collected data from one center experience in Italy enrolled from January 2011 to December 2016. The study included 62 patients [mean age 74±11years, 43 men (69%)] with MR of at least grade3+. Most of the patients had functional MR, were in New York Heart Association (NYHA) functional class III or IV, with a large portion (78%) of mild-to-moderate Tricuspid Regurgitation (TR). One or more clips were implanted in 67 procedures (62 patients). Results and Conclusions: Severity of MR was reduced in all successfully treated patients,54(90%) were discharged with MR≤2+ (primary effectiveness endpoint). Clinical 1-month follow-up data showed an improvement in NYHA functional class (42 patients (70%) in NYHA class I-II). 60 of 62 (97 %) successfully treated patients were free from death and mitral valve surgery at 1-month follow-up. MitraClip therapy reduces functional MR with acute MR reduction to <2+ in the great majority of patients, with a large freedom from death, surgery or recurrent MR in a great portion of patients.

Keywords: MitraClip, mitral regurgitation, heart valves, catheter-based therapy

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Authors: Kolja Them, Johannes Salamon, Harald Ittrich, Michael Kaul, Tobias Knopp

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Superparamagnetic iron oxide nanoparticles (SPIONs) are nanoscale magnets which can be biologically functionalized for biomedical applications. Stem cell therapies to repair damaged tissue, magnetic fluid hyperthermia for cancer therapy and targeted drug delivery based on SPIONs are prominent examples where the visualization of a preferably low concentrated SPION distribution is essential. In 2005 a new method for tomographic SPION imaging has been introduced. The method named magnetic particle imaging (MPI) takes advantage of the nanoparticles magnetization change caused by an oscillating, external magnetic field and allows to directly image the time-dependent nanoparticle distribution. The SPION magnetization can be changed by the electron spin dynamics as well as by a mechanical rotation of the nanoparticle. In this work different calibration methods in MPI are investigated for image reconstruction of magnetically labeled stem cells. It is shown that a calibration using rotationally immobilized SPIONs provides a higher quality of stem cell images with fewer artifacts than a calibration using mobile SPIONs. The enhancement of the image quality and the reduction of artifacts enables the localization and identification of a smaller number of magnetically labeled stem cells. This is important for future medical applications where low concentrations of functionalized SPIONs interacting with biological matter have to be localized.

Keywords: biomedical imaging, iron oxide nanoparticles, magnetic particle imaging, stem cell imaging

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Authors: Tuba Denkceken, Ayse Nur Sarı, Volkan Ihsan Tore, Mahmut Denkceken

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The aim of the presented study was to develop a newly motorized spectroscopy system. Our system is composed of probe and motor parts. The probe part consists of bioimpedance and fiber optic components that include two platinum wires (each 25 micrometer in diameter) and two fiber cables (each 50 micrometers in diameter) respectively. Probe was examined on tissue phantom (polystyrene microspheres with different diameters). In the bioimpedance part of the probe current was transferred to the phantom and conductivity information was obtained. Adjacent two fiber cables were used in the fiber optic part of the system. Light was transferred to the phantom by fiber that was connected to the light source and backscattered light was collected with the other adjacent fiber for analysis. It is known that the nucleus expands and the nucleus-cytoplasm ratio increases during the cancer progression in the cell and this situation is one of the most important criteria for evaluating the tissue for pathologists. The sensitivity of the probe to particle (nucleus) size in phantom was tested during the study. Spectroscopic data obtained from our system on phantom was evaluated by multivariate statistical analysis. Thus the information about the particle size in the phantom was obtained. Bioimpedance and fiber optic experiments results which were obtained from polystyrene microspheres showed that the impedance value and the oscillation amplitude were increasing while the size of particle was enlarging. These results were compatible with the previous studies. In order to motorize the system within the motor part, three driver electronic circuits were designed primarily. In this part, supply capacitors were placed symmetrically near to the supply inputs which were used for balancing the oscillation. Female capacitors were connected to the control pin. Optic and mechanic switches were made. Drivers were structurally designed as they could command highly calibrated motors. It was considered important to keep the drivers’ dimension as small as we could (4.4x4.4x1.4 cm). Then three miniature step motors were connected to each other along with three drivers. Since spectroscopic techniques are quantitative methods, they yield more objective results than traditional ones. In the future part of this study, it is planning to get spectroscopic data that have optic and impedance information from the cell culture which is normal, low metastatic and high metastatic breast cancer. In case of getting high sensitivity in differentiated cells, it might be possible to scan large surface tissue areas in a short time with small steps. By means of motorize feature of the system, any region of the tissue will not be missed, in this manner we are going to be able to diagnose cancerous parts of the tissue meticulously. This work is supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) through 3001 project (115E662).

Keywords: motorized spectroscopy, phantom, scanning system, tissue scanning

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Authors: Amin Jabbari

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The state of the art in major 3D printing technologies, such as powder-based and slurry based, has led researchers to investigate the ability to fabricate bone scaffolds for bone tissue engineering using biomaterials. In addition, 3D printing technology can simulate mechanical and biological surface properties and print with high precision complex internal and external structures that match their functional properties. Polymer matrix composites reinforced with particulate bioceramics, hydrogels reinforced with particulate bioceramics, polymers coated with bioceramics, and non-porous bioceramics are among the materials that can be investigated for bone scaffold printing. Furthermore, it was shown that the introduction of high-density micropores into the sparingly dissolvable CSiMg10 and dissolvable CSiMg4 shell layer inevitably leads to a nearly 30% reduction in compressive strength, but such micropores can easily influence the ion release behavior of the scaffolds. Also, biocompatibility tests such as cytotoxicity, hemocompatibility and genotoxicity were tested on printed parts. The printed part was tested in vitro, and after 24-26 h for cytotoxicity, and 4h for hemocompatibility test, the CSiMg4@CSiMg10-p scaffolds were found to have significantly higher osteogenic capability than the other scaffolds of implantation. Overall, these experimental studies demonstrate that 3D printed, additively-manufactured bioceramic calcium (Ca)-silicate scaffolds with appropriate pore dimensions are promising to guide new bone ingrowth.

Keywords: AM, 3D printed implants, bioceramic, tissue engineering

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Authors: Gema Gómez-Casado, Alba Rodríguez-Muñoz, Virginia Mela-Rivas, Pallavi Kompella, Francisco José Tinahones-Madueña, Isabel Moreno-Indias, Almudena Ortega-Gómez

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Obesity is a high-priority health problem worldwide due to its high prevalence. The proportion of obese and overweight subjects in industrialized countries exceeds half of the population in most cases. Beyond the metabolic problem, obesity boosts inflammation levels in the organism. The gut microbiota, considered an organ by itself, controls a high variety of processes at a systemic level. In fact, the microbiota interacts closely with the immune system, being crucial in determining the maturation state of neutrophils, key effectors of the innate immune response. It is known that changes in the diet exert strong effects on the variety and activity of the gut microbiota. The effect that those changes have on the axis microbiota-immune response is an unexplored field. In this study, 10 patients with obesity (weight 114,3 ± 14,5Kg, BMI 40,47±3,66) followed a Mediterranean-hypocaloric diet for 3 months, reducing their initial weight by 12,71 ± 3%. A transplant of microbiota from these patients before and after the diet was performed into wild type “germ-free” mice (n=10/group), treated with antibiotics. Six weeks after the transplant, mice were euthanized, and the presence of cells from the innate immune system were analysed in different organs (bone marrow, blood, spleen, visceral adipose tissue, and intestine) by flow cytometry. No differences were observed in the number of myeloid cells in bone marrow, blood, spleen, or visceral adipose tissue of mice transplanted with patient’s microbiota before and after following the Mediterranean diet. However, the intestine of mice that received post-diet microbiota presented a marked decrease in the number of neutrophils (whose presence is associated with tissue inflammation), as well as macrophages. In line with these findings, intestine monocytes from mice with post-diet microbiota showed a less inflammatory profile (lower Ly6Gˡᵒʷ proportion of cells). These results point toward a decrease in the inflammatory state of the intestinal tissue, derived from changes in the gut microbiota, which occurred after a 3-month Mediterranean diet.

Keywords: obesity, nutrition, Mediterranean diet, gut microbiota, immune system

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Authors: Emma K. Sales, Nilda G. Butardo

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The project was undertaken to determine the effects of modified tissue culture protocols e.g. age of culture and hormone levels (2,4-D) in generating somaclonal variation. Moreover, the utility of molecular markers (SSR and MSAP) in sorting off types/somaclones were investigated. Results show that somaclonal variation is in effect due to prolonged subculture and high 2,4-D concentration. The resultant variation was observed to be due to high level of methylation events specifically cytosine methylation either at the internal or external cytosine and was identified by methylation sensitive amplification polymorphism (MSAP). Simple sequence repeats (SSR) on the other hand, was able to associate a marker to a trait of interest. These therefore, show that molecular markers can be an important tool in sorting out variation/mutants at an early stage.

Keywords: methylation, MSAP, somaclones, SSR, subculture, 2, 4-D

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Authors: Ilma Robo, Saimir Heta, Vera Ostreni, Elsaida Agrushi, Eduart Kapaj

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Introduction: Cyclic hormonal fluctuations are known from literature to have a clinically visible effects on gingival tissue reactions, to the diagnosed processes of gingival inflammation. Materials and methods: At a total of 47 female patients, ad-hock presented at the University Clinic, were recorded data on effect of hormonal oscillations at periodontal treatment protocol. Oral examination was performed on soft tissue of gingiva and the oral mucous membrane, always respecting the air-drying procedure and then checking with free eye differences in oral mucosal relief. After the patients were informed about the study protocol, the purpose of the study and the ongoing procedure, verbal consensus was required. Results: The study was conducted in a total of 47 patients, out of which 13 patients were under the gingivitis classification, and 24 patients under the periodontal classification. Patients included in the study are divided by age, cycle week respectively 1,2,3 and 4.The younger age of female patients is more prone to the appearance of gingivitis, which is further aggravated by the effects of sexual hormones and the effect of the controlled or non-regulated fluctuations of the latter. Conclusions: The healing process is more fuel-intensive in the absence of high hormone levels, as they are these pro-inflammatory hormones, both in or near the ho Younger women are more open to volunteering in studies that record individual and study data that may last in time.

Keywords: gingiva, hormonal oscillations, female patients, mucosa, periodontal non-surgical treatment

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Authors: Hyun KI Kang, Hi Won Jeong

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The gas turbine operates for a long period of time under harsh, cyclic conditions of high temperature and pressure, where high turbine inlet temperature (TIT) can range from 1273 to 1873K. Therefore, Ni-base superalloys such as IN738, IN939, Rene 45, Rene 71, Rene 80, Mar M 247, CM 247, and CMSX-4 with excellent mechanical properties and resistance to creep, corrosion and oxidation at high temperatures are indeed used. Among the alloying additions for these alloys, aluminum (Al) and titanium (Ti) form gamma prime and enhance the high-temperature properties. However, when crack-damaged high-temperature turbine components such as blade and vane are repaired by fusion welding, they cause cracks. For example, when arc welding is applied to certain superalloys that contain Al and Ti with more than 3 wt.% and T3.5 wt%, respectively, such as IN738, IN939, Rene 80, Mar M 247, and CM 247, aging cracks occur. Therefore, repair technologies using diffusion brazing, which has less heat input into the base material, are being developed. Analysis of microstructural evolution of the brazed joints with a base metal of IN 939 Ni-base superalloy using brazing different filler metals was also carried out using X-ray diffraction, OEM, SEM-EDS, and EPMA. Stress rupture and high-temperature tensile strength properties were also measured to analyze the effects of different brazing heat cycles. The boron amount in the diffusion-affected zone (DAZ) was decreased towards the base metal and the formation of borides at grain boundaries was detected through EPMA.

Keywords: gas turbine, diffusion brazing, superalloy, gas turbine repair

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Authors: Majid Khan

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Introduction: In this era of microsurgery, free flap holds a remarkable spot in reconstructive surgery. A free flap is well suited for composite defects as it provides sufficient and well-vascularized tissue for coverage. We report our experience with the use of the free flaps for the reconstruction of composite defects. Methods: This is a retrospective case series (chart review) of patients who underwent reconstruction of composite defects with a free flap at Aga Khan University Hospital, Karachi (Pakistan) from January 01, 2015, to December 31, 2019. Data were collected for patient demographics, size of the defect, size of flap, recipient vessels, postoperative complications, and outcome of the free flap. Results: Over this period, 532 free flaps are included in this study. The overall success rate is 95.5%. The mean age of the patient was 44.86 years. In 532 procedures, there were 448 defects from tumor ablation of head and neck cancer. The most frequent free flap was the anterolateral thigh flap in 232 procedures. In this study, the risk factor hypertension (p=0.004) was found significant for wound dehiscence, preop radiation/chemotherapy (p=0.003), and malnutrition (p=0.005) were found significant for fistula formation. Malnutrition (p=0.02) and use of vein grafts (p=0.025) were significant factors for flap failure. Conclusion: Free tissue transfer is a reliable option for the reconstruction of large and composite defects. Hypertension, malnutrition, and preoperative radiotherapy can cause significant morbidity.

Keywords: free flap, free flap failure, risk factors for flap failure, free flap outcome

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Authors: Sandra Pietri, Helene Dubout, Sabrina Ena, Candice Hoste, Enrico Bastianelli

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Bone Therapeutics is a bone cell therapy company addressing high unmet medical needs in the field of bone fracture repair, more specifically in non-union and delayed-union fractures where the bone repair process is impaired. The company has developed a unique allogeneic osteoblastic cell product (ALLOB®) derived from bone marrow which is currently tested in humans in the indication of delayed-union fractures. The purpose of our study was to directly compare ALLOB® vs. non-differentiated mesenchymal stem cells (MSC) for their in vitro osteogenic characteristics and their in vivo osteogenic potential in order to determine which cellular type would be the most adapted for bone fracture repair. Methods: Healthy volunteers’ bone marrow aspirates (n=6) were expended (i) into BM-MSCs using a complete MSC culture medium or (ii) into ALLOB® cells according to its manufacturing process. Cells were characterized in vitro by morphology, immunophenotype, gene expression and differentiation potential. Additionally, their osteogenic potential was assessed in vivo in the subperiosteal calvaria bone formation model in nude mice. Results: The in vitro side-by-side comparison studies showed that although ALLOB® and BM-MSC shared some common general characteristics such as the 3 minimal MSC criteria, ALLOB® expressed significantly higher levels of chondro/osteoblastic genes such as BMP2 (fold change (FC) > 100), ALPL (FC > 12), CBFA1 (FC > 3) and differentiated significantly earlier than BM-MSC toward the osteogenic lineage. Moreover the bone formation model in nude mice demonstrated that used at the same cellular concentration, ALLOB® was able to induce significantly more (160% vs.107% for control animals) bone formation than BM-MSC (118% vs. 107 % for control animals) two weeks after administration. Conclusion: Our side-by-side comparison studies demonstrated that in vitro and in vivo, ALLOB® displays superior osteogenic capacity to BM-MScs and is therefore a better candidate for the treatment of bone fractures.

Keywords: gene expression, histomorphometry, mesenchymal stem cells, osteogenic differentiation potential, preclinical

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Authors: Noha Mohammed Ismael Awad Eladal, Aala Shoukry Emara

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Background: Wound healing after dental implant surgery is critical to the procedure's success. The aim of this study was to explore the effects of rutin+vitamin C supplementation in wound healing following the placement of dental implants. Methodology: There were 20 participants in this randomized controlled clinical trial who needed dental implants to replace missing teeth. Patients were divided into two groups, and group A received dental implants. Group B received dental implants with vitamin C administration. Follow-up appointments were performed on day 3, day 7, and day 14 post-surgery, during which soft tissue healing and pain response scores were evaluated using the visual analog scale. Postoperative digital panoramas were taken immediately after surgery, 3 months and 6 months postoperatively. Changes in bone density along with the bone-implant interface at the mesial, distal and apical sides were assessed using the digora software. Results: An independent t-test was used to compare the means of variables between the two groups. At the same time, repeated measures were employed to compare the means of variables between two groups. ANOVA was used to compare bone density for the same group at different dates. Significant increased differences were observed at the mesial, distal and apical sides Surrounding the implants of both groups per time. However, the rate of increase was significantly higher in group B The mean difference at the mesial side after 6 months was 21.99 ± 5.48 in the group B and 14.21 ± 4.95 in group A, while it read 21.74 ± 3.56 in the group B and 10.78 ± 3.90 in group A at the distal side and was 18.90 ± 5.91 in the group B and 10.39 ± 3.49 group A at the apical side. Significance was recorded at P = 0.004, P = 0.0001, and 0.001 at the mesial, distal and apical sides respectively. The mean pain score and wound healing were significantly higher in group A as compared to group B, respectively. Conclusion: The rutin c + vitamin c group significantly promoted bone healing and speeded up the osseointegration process and improved soft tissue healing.

Keywords: osseointegration, soft tissue, rutin c, dental implant

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Authors: Shackira Am, Jos T. Puthur

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The phytostabilization potential of a halophyte Acanthus ilicifolius L. has been evaluated with special attention to the nutritional as well as anatomical adaptations developed by the plant. Distribution of essential elements influenced by the excess Zn²⁺ ions in the root tissue was studied by FEG-SEM EDX microanalysis. Significant variations were observed in the uptake and allocation of mineral elements like Mg, P, K, S, Na, Si and Al in the root of A. ilicifolius. The increase in S is in correlation with the increased synthesis of glutathione which might be involved in the biosynthesis of phytochelatins. This in turn might be aiding the plant to tolerate the adverse environmental conditions by stabilizing the excess Zn in the root tissue itself. Moreover it is revealed that most of the Zn were accumulated towards the central region near the vascular tissue. Treatment with ZnSO₄ in A. ilicifolius caused significant increase in the number of glandular trichomes on the adaxial leaf surface as compared to the leaves of control plants. In addition to this, A. ilicifolius when treated with ZnSO₄, exhibited a deeply stained layer of cells immediate to the endodermis, forming more or less a ring like structure around the xylem vessels. Phloem cells in these plants were crushed/reduced in numbers. There were no such deeply stained cells forming a ring around the xylem vessels in the control plants. These adaptive responses make the plant a suitable candidate for the phytostabilization of Zn. In addition the nutritional adjustment of the plant equips them for a better survival under increased concentration of Zn²⁺.

Keywords: Acanthus ilicifolius, mineral elements, phytostabilization, zinc

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Authors: Ling-Ling E., Hong-Chen Liu, Dong-Sheng Wang, Fang Su, Xia Wu, Zhan-Ping Shi, Yan Lv, Jia-Zhu Wang

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Objective: The objective of the present study is to evaluate the capacity of a tissue-engineered bone complex of recombinant human bone morphogenetic protein 2 (rhBMP-2) mediated dental pulp stem cells (DPSCs) and nano-hydroxyapatite/collagen/poly(L-lactide)(nHAC/PLA) to reconstruct critical-size alveolar bone defects in New Zealand rabbit. Methods: Autologous DPSCs were isolated from rabbit dental pulp tissue and expanded ex vivo to enrich DPSCs numbers, and then their attachment and differentiation capability were evaluated when cultured on the culture plate or nHAC/PLA. The alveolar bone defects were treated with nHAC/PLA, nHAC/PLA+rhBMP-2, nHAC/PLA+DPSCs, nHAC/PLA+DPSCs+rhBMP-2, and autogenous bone (AB) obtained from iliac bone or were left untreated as a control. X-ray and a polychrome sequential fluorescent labeling were performed post-operatively and the animals were sacrificed 12 weeks after operation for histological observation and histomorphometric analysis. Results: Our results showed that DPSCs expressed STRO-1 and vementin, and favoured osteogenesis and adipogenesis in conditioned media. DPSCs attached and spread well, and retained their osteogenic phenotypes on nHAC/PLA. The rhBMP-2 could significantly increase protein content, alkaline phosphatase (ALP) activity/protein, osteocalcin (OCN) content, and mineral formation of DPSCs cultured on nHAC/PLA. The X-ray graph, the fluorescent, histological observation and histomorphometric analysis showed that the nHAC/PLA+DPSCs+rhBMP-2 tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than nHAC/PLA, nHAC/PLA+rhBMP-2 and nHAC/PLA+DPSCs, or even autologous bone. Implanted DPSCs contribution to new bone were detected through transfected eGFP genes. Conclutions: Our findings indicated that stem cells existed in adult rabbit dental pulp tissue. The rhBMP-2 promoted osteogenic capability of DPSCs as a potential cell source for periodontal bone regeneration. The nHAC/PLA could serve as a good scaffold for autologous DPSCs seeding, proliferation and differentiation. The tissue-engineered bone complex with nHAC/PLA, rhBMP-2, and autologous DPSCs might be a better alternative to autologous bone for the clinical reconstruction of periodontal bone defects.

Keywords: nano-hydroxyapatite/collagen/poly (L-lactide), dental pulp stem cell, recombinant human bone morphogenetic protein, bone tissue engineering, alveolar bone

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Authors: Amin Davoudi

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Aim: New approaches have been introduced to improve soft tissue indices of the dental implants. This systematic review aimed to investigate the effect of computer-aided design and computer-assisted manufacture (CAD/CAM) zirconia (Zr) implant abutments on periodontal aspects. Materials and Methods: Five electronic databases were searched thoroughly based on prior defined MeSH and non-MeSH keywords. Clinical studies were collected via hand searches in English language journals up to September 2020. Interproximal papilla stability, papilla recession, pink and white esthetic score (PES, WES), bone and gingival margin levels, color, and contour of soft tissue were reviewed. Results: The initial literature search yielded 412 articles. After the evaluation of abstracts and full texts, six studies were eligible to be screened. The study design of the included studies was a prospective cohort (n=3) and randomized clinical trial (n=3). The outcome was found to be significantly better for Zr than titanium abutments, however, the studies did not show significant differences between stock and CAD/CAM abutments. Conclusion: Papilla fill, WES, PES, and the distance from the contact point to dental crest bone of adjacent tooth and inter-tooth–implant distance were not significantly different between Zr CAD/CAM and Zr stock abutments. However, soft tissue stability and recession index were better in Zr CAD/CAM abutments.

Keywords: zirconia, CADCAM, periodental, implant

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Authors: Adrian Ionut Nicoara, Denisa Ionela Ene, Alina Maria Holban, Cristina Busuioc

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At present, the development of materials with biomedical applications is a domain of interest that will produce a full series of benefits in engineering and medicine. In this sense, it is required to use a natural material, and this paper is focused on the development of a composite material based on bacterial cellulose – hydroxyapatite and silver nanoparticles with applications in hard tissue. Bacterial cellulose own features like biocompatibility, non-toxicity character and flexibility. Moreover, the bacterial cellulose can be conjugated with different forms of active silver to possess antimicrobial activity. Hydroxyapatite is well known that can mimic at a significant level the activity of the initial bone. The material was synthesized by using an ultrasound probe and finally characterized by several methods. Thereby, the morphological properties were analyzed by using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Because the synthesized material has medical application in restore the tissue and to fight against microbial invasion, the samples were tested from the biological point of view by evaluating the biodegradability in phosphate-buffered saline (PBS) and simulated body fluid (SBF) and moreover the antimicrobial effect was performed on Gram-positive bacterium Staphylococcus aureus, Gram-negative bacterium Escherichia coli, and fungi Candida albicans. The results reveal that the obtained material has specific characteristics for bone regeneration.

Keywords: bacterial cellulose, biomaterials, hydroxyapatite, scaffolds materials

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Authors: Ghasem Yazdanpanah, Mona Kakavand, Hassan Niknejad

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Objectives: An important issue in tissue engineering (TE) is hemocompatibility. The current engineered vessels are seriously at risk of thrombus formation and stenosis. Amnion (AM) is the innermost layer of fetal membranes that consists of epithelial and mesenchymal sides. It has the advantages of low immunogenicity, anti-inflammatory and anti-bacterial properties as well as good mechanical properties. We recently introduced the amnion as a natural biomaterial for tissue engineering. In this study, we have evaluated hemocompatibility of amnion as potential biomaterial for tissue engineering. Materials and Methods: Amnions were derived from placentas of elective caesarean deliveries which were in the gestational ages 36 to 38 weeks. Extracted amnions were washed by cold PBS to remove blood remnants. Blood samples were obtained from healthy adult volunteers who had not previously taken anti-coagulants. The blood samples were maintained in sterile tubes containing sodium citrate. Plasma or platelet rich plasma (PRP) were collected by blood sample centrifuging at 600 g for 10 min. Hemocompatibility of the AM samples (n=7) were evaluated by measuring of activated partial thromboplastin time (aPTT), prothrombin time (PT), hemolysis, and platelet aggregation tests. P-selectin was also assessed by ELISA. Both epithelial and mesenchymal sides of amnion were evaluated. Glass slide and expanded polytetrafluoroethylene (ePTFE) samples were defined as control. Results: In comparison with glass as control (13.3 ± 0.7 s), prothrombin time was increased significantly while each side of amnion was in contact with plasma (p<0.05). There was no significant difference in PT between epithelial and mesenchymal surfaces (17.4 ± 0.7 s vs. 15.8 ± 0.7 s, respectively). However, aPPT was not significantly changed after incubation of plasma with amnion epithelial and mesenchymal surfaces or glass (28.61 ± 1.39 s, 31.4 ± 2.66 s, glass, 30.76 ± 2.53 s, respectively, p>0.05). Amnion surfaces, ePTFE and glass samples have less hemolysis induction than water considerably (p<0.001), in which no differences were detected. Platelet aggregation measurements showed that platelets were less stimulated by the amnion epithelial and mesenchymal sides, in comparison with ePTFE and glass. In addition, reduction in amount of p-selectin, as platelet activation factor, after incubation of samples with PRP indicated that amnion has less stimulatory effects on platelets than ePTFE and glass. Conclusion: Amnion as a natural biomaterial has the potential to be used in tissue engineering. Our results suggest that amnion has appropriate hemocompatibility to be employed as a vascular substitute.

Keywords: amnion, hemocompatibility, tissue engineering, biomaterial

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Authors: Mostafa Mabrouk, Basma E. Abdel-Ghany, Mona Moaness, Bothaina M. Abdel-Hady, Hanan H. Beherei

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Tissue engineering became a promising field for bone repair and regenerative medicine in which cultured cells, scaffolds and osteogenic inductive signals are used to regenerate tissues. The annual cost of treating bone defects in Egypt has been estimated to be many billions, while enormous costs are spent on imported bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. The current study is aimed at developing a more strategic approach in order to speed-up recovery after bone damage. This will reduce the risk of fatal surgical complications and improve the quality of life of people affected with such fractures. 3D scaffolds loaded with cheap nano-particles that possess an osteogenic effect were prepared by nano-electrospinning. The Microstructure and morphology characterizations of the 3D scaffolds were monitored using scanning electron microscopy (SEM). The physicochemical characterization was investigated using X-ray diffractometry (XRD) and infrared spectroscopy (IR). The Physicomechanical properties of the 3D scaffold were determined by a universal testing machine. The in vitro bioactivity of the 3D scaffold was assessed in simulated body fluid (SBF). The bone-bonding ability of novel 3D scaffolds was also evaluated. The obtained nanofibrous scaffolds demonstrated promising microstructure, physicochemical and physicomechanical features appropriate for enhanced bone regeneration. Therefore, the utilized nanomaterials loaded with the drug are greatly recommended as cheap alternatives to growth factors.

Keywords: bone regeneration, cheap scaffolds, nanomaterials, active molecules

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Authors: Sisi Xia, Dezhuan Tao

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Urban Double Reform is an effective means to improve the quality of ecological space, based on improving the living environment and urban functions and promoting the organic integration of the city and nature. This paper takes the design of Qinyang Wetland Park in Jiaozuo, Henan Province, as an example, attempting to closely link the ecological restoration of wetland with the urban culture and to extend the urban spirit of the ancient county of Qinyang while purifying the ecological water system. This design uses ecological technology to repair underwater forests and underwater turf, rapidly improving the quality of urban water without biological side effects. The ecological grass slope is used to create multiple bank forms, combining with a number of hydrophilic platforms to provide a good view of the public. Through the placement of ecological education bases, urban cultural exhibition halls, and other means, the cultural value of wetland parks will be enhanced, and the citizens will return to nature and experience the ecology and appreciate the charm of urban culture in the ecological space. Repair the ecosystem, sculpt the urban culture, let the public return to nature, experience the ecology, and experience the charm of urban culture in the ecological space.

Keywords: urban double reform, ecological space, improvement strategy, wetland park design

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Authors: Amina Ben Abla, Sylvie Changotade, Geraldine Rohman, Guilhem Boeuf, Cyrine Dridi, Ahmed Elmarjou, Florence Dufour, Didier Lutomski, Abdellatif Elm’semi

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Understanding cell adhesion and interaction with the extracellular matrix is essential for biomedical and biotechnological applications, including the development of biomaterials. In recent years, numerous biomaterials have emerged and were used in the field of tissue engineering. Nevertheless, the lack of interaction of biomaterials with cells still limits their bio-integration. Thus, the design of bioactive biomaterials to improve cell attachment and proliferation is of growing interest. In this study, bio-functionalized material was developed combining a synthetic polymer scaffold surface with selected domains of type III human fibronectin (FNIII-DOM) to promote cell adhesion and proliferation. Bioadhesive ligand includes cell-binding domains of human fibronectin, a major ECM protein that interacts with a variety of integrins cell-surface receptors, and ECM proteins through specific binding domains were engineered. FNIII-DOM was produced in bacterial system E. coli in 5L fermentor with a high yield level reaching 20mg/L. Bioactivity of the produced fragment was validated by studying cellular adhesion of human cells. The adsorption and immobilization of FNIII-DOM onto the polymer scaffold were evaluated in order to develop an innovative biomaterial.

Keywords: biomaterials, cellular adhesion, fibronectin, tissue engineering

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Authors: Olfat Mohamed Hussien Yousef

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Tamoxifen (TM) is a synthetic non-steroidal antiestrogen. It is one of the most effective drugs for treatment of estrogen-dependent cancer by binding to estrogen receptors, suppressing of epithelial proliferation and as a chemotherapeutic agent. Recently, more attention has been paid to the protective effects of natural antioxidants against toxicities induced by anti-cancer drugs involving free radical-mediated oxidative stress and tissue injury. Vitamin C is a potent antioxidant that has the ability to scavenge factors causing free radical formation in animals receiving tamoxifen. The present study aims at pinpointing the TM-induced histopathological and ultrastructural changes in the kidneys and to assess the possible chemoprotective role of vitamin C against such TM-induced microscopic changes. Thirty adult male CD-1 mice, 25-30 g in weight and 3 months old, were divided into three groups. The first group served as control. The second group received the therapeutic dose of TM at daily oral dose of 40 mg/kg body weight for 28 days. The third group received the therapeutic dose of vitamin C at a daily dose of 500 mg/kg body weight simultaneously with the therapeutic dose of TM used in group two for 28 days. Animals were sacrificed and kidney samples were obtained and processed for histological and ultrastructural examination. Histological changes induced by TM included damage of the renal corpuscles including obliteration of the subcapsular space, congestion of the glomerular blood capillaries, segmental mesangial cell proliferation with matrix expansion, capsular adhesions with the glomerular tuft especially at the urinary pole of the corpuscles. Moreover, some proximal and distal tubules suffered various degrees of degeneration in some lining cells. Haemorrhage and inflammatory cell infiltration were also observed in the intertubular spaces. Ultrastructural observations revealed damage of the parietal epithelium of Bowman’s capsule, fusion and destruction of the foot processes of podocytes and great increase of mesangial cells and mesangial matrix. The cells of the proximal convoluted tubules displayed marked destruction of the microvilli constituting the brush borders and degeneration of the mitochondria; besides, abundant lysosomes, numerous vacuoles and pyknotic nuclei were observed. The distal convoluted tubules displayed marked distruction of both the basal infolding and the mitochondria in some areas. Histological and ultrastructural results revealed that treatment of male mice with TM simultaneously with vitamin C led to apparent repair of the injured renal tissue. This might suggest that vitamin C (an antioxidant agent) can minimize the toxic effects of TM (an antiestrogen).

Keywords: tamoxifen, vitamin c, mammalian kidney, histology, ultrastructure

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Authors: Sudhir Kumar Sharma, Abiy D. Woldetsadik, Mazin Magzoub, Ramesh Jagannathan

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It is well known that bioactive ceramics exhibit specific biological affinities, especially in the area of tissue re-generation. In this context, we report the development of an eminently scalable, novel, supercritical CO₂ based process for the fabrication of hierarchically porous 'soft' CaCO₃ scaffolds. Porosity at the macro, micro, and nanoscales was obtained through process optimization of the so-called 'coffee-ring effect'. Exposure of these CaCO₃ scaffolds to monocytic THP-1 cells yielded negligible levels of tumor necrosis factor-alpha (TNF-α) thereby confirming the lack of immunogenicity of the scaffolds. ECM protein treatment of the scaffolds showed enhanced adsorption comparable to standard control such as glass. In vitro studies using osteoblast precursor cell line, MC3T3, also demonstrated the cytocompatibility of hierarchical porous CaCO₃ scaffolds.

Keywords: supercritical CO2, CaCO3 scaffolds, coffee-ring effect, ECM proteins

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Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: Amr A. Fouad, Hamed A. Alwadaani, Iyad Jresat

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The present study investigated the protective effect of thymoquinone (TQ), against cadmium-induced kidney injury in rats. Cadmium chloride (1.2 mg Cd/kg/day, s.c.), was given for nine weeks. TQ treatment (40 mg/kg/day, p.o.) started on the same day of cadmium administration and continued for nine weeks. TQ significantly decreased serum creatinine, renal malondialdehyde and nitric oxide, and significantly increased renal reduced glutathione in rats received cadmium. Histopathological examination showed that TQ markedly minimized renal tissue damage induced by cadmium. Immunohistochemical analysis revealed that TQ markedly decreased the cadmium-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, and caspase-3 in renal tissue. It was concluded that TQ significantly protected against cadmium nephrotoxicity in rats, through its antioxidant, antiinflammatory, and antiapoptotic actions.

Keywords: thymoquinone, cadmium, kidney, rats

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Authors: C. Gallottini, W. Di Mari, A. Amaddeo, K. Barbaro, A. Dolci, G. Dolci, L. Gallottini, G. Barraco, S. Eramo

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A group of 10 dogs (group A) with Periodontal Disease in the third stage, were subjected to regenerative therapy of periodontal tissues, by use of nano hydroxy apatite (NHA). These animals induced by general anesthesia, where treated by ultrasonic scaling, root planning, and at the end by a mucogingival flap in which it was applied NHA. The flap was closed and sutured with simple steps. Another group of 10 dogs (group B), control group, was treated only by scaling and root planning. No patient was subjected to antibiotic therapy. After three months, a check was made by inspection of the oral cavity, radiography and bone biopsy at the alveolar level. Group A showed a total restitutio ad integrum of the periodontal structures, and in group B still mild gingivitis in 70% of cases and 30% of the state remains unchanged. Numerous experimental studies both in animals and humans have documented that the grafts of porous hydroxyapatite are rapidly invaded by fibrovascular tissue which is subsequently converted into mature lamellar bone tissue by activating osteoblast. Since we acted on the removal of necrotic cementum and rehabilitating the root tissue by polishing without intervention in the ligament but only on anatomical functional interface of cement-blasts, we can connect the positive evolution of the clinical-only component of the cement that could represent this perspective, the only reason that Periodontal Disease become a Cement Disease, while all other clinical elements as nothing more than a clinical pathological accompanying.

Keywords: nanoidroxiaphatite, parodontal disease, cement disease, regenerative therapy

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Authors: Raziyeh Mohammadi

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At present, nanoparticles are used for various biomedical applications where they facilitate laboratory diagnostics and therapeutics. The performance of nanoparticles for biomedical applications is often assessed by their narrow size distribution, suitable magnetic saturation, and low toxicity effects. Superparamagnetic iron oxide nanoparticles have received great attention due to their applications as contrast agents for magnetic resonance imaging (MRI. (Processes in the tissue where the blood brain barrier is intact in this way shielded from the contact to this conventional contrast agent and will only reveal changes in the tissue if it involves an alteration in the vasculature. This technique is very useful for detecting tumors and can even be used for detecting metabolic functional alterations in the brain, such as epileptic activity.SPIONs have found application in Magnetic Resonance Imaging (MRI) and magnetic hyperthermia. Unlike bulk iron, SPIONs do not have remnant magnetization in the absence of the external magnetic field; therefore, a precise remote control over their action is possible.

Keywords: nanoparticles, MRI, biomedical, iron oxide, spions

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