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  1. Fulltext Effect of Different Collection Times of Dermal Fibroblast Conditioned Medium (DFCM) on In Vitro Re-Epithelialisation Process
    Abdul Ghani N', Razali RA, Chowdhury SR, Fauzi MB, Bin Saim A, Ruszymah BHI, et al.
    Biomedicines, 2022 Dec 09;10(12).
    PMID: 36551960 DOI: 10.3390/biomedicines10123203
    A key event in wound healing is re-epithelialisation, which is mainly regulated via paracrine signalling of cytokines, chemokines, and growth factors secreted by fibroblasts. Fibroblast-secreted factors can be collected from the used culture medium, known as dermal fibroblast conditioned medium (DFCM). The goal of this study was to optimise the culture condition to acquire DFCM and evaluate its effect on keratinocyte attachment, proliferation, migration, and differentiation. Confluent fibroblasts were cultured with serum-free keratinocyte-specific (DFCM-KM) and fibroblast-specific (DFCM-FM) medium at different incubation times (Days 1, 2, and 3). DFCM collected after 3 days of incubation (DFCM-KM-3 and DFCM-FM-3) contained a higher protein concentration compared to other days. Supplementation of DFCM-KM-3 enhanced keratinocyte attachment, while DFCM-FM-3 significantly increased the keratinocyte wound-healing rate, with an increment of keratinocyte area and collective cell migration, which was distinctly different from DFCM-KM-3 or control medium. Further analysis confirmed that the presence of calcium at higher concentrations in DFCM-FM facilitated the changes. The confluent dermal fibroblasts after 3 days of incubation with serum-free culture medium produced higher proteins in DFCM, resulting in enhanced in vitro re-epithelialisation. These results suggest that the delivery of DFCM could be a potential treatment strategy for wound healing.
  2. Cytotoxic evaluation of biomechanically improved crosslinked ovine collagen on human dermal fibroblasts
    Awang MA, Firdaus MA, Busra MB, Chowdhury SR, Fadilah NR, Wan Hamirul WK, et al.
    Biomed Mater Eng, 2014;24(4):1715-24.
    PMID: 24948455 DOI: 10.3233/BME-140983
    Earlier studies in our laboratory demonstrated that collagen extracted from ovine tendon is biocompatible towards human dermal fibroblast. To be able to use this collagen as a scaffold in skin tissue engineering, a mechanically stronger scaffold is required that can withstand manipulation before transplantation. This study was conducted to improve the mechanical strength of this collagen sponge using chemical crosslinkers, and evaluate their effect on physical, chemical and biocompatible properties. Collagen sponge was crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and glutaraldehyde (GA). Tensile test, FTIR study and mercury porosimetry were used to evaluate mechanical properties, chemical property and porosity, respectively. MTT assay was performed to evaluate the cytotoxic effect of crosslinked collagen sponge on human dermal fibroblasts. The FTIR study confirmed the successful crosslinking of collagen sponge. Crosslinking with EDC and GA significantly increased the mechanical strength of collagen sponge, with GA being more superior. Crosslinking of collagen sponge significantly reduced the porosity and the effect was predominant in GA-crosslinked collagen sponge. The GA-crosslinked collagen showed significantly lower, 60% cell viability towards human dermal fibroblasts compared to that of EDC-crosslinked collagen, 80% and non-crosslinked collagen, 100%. Although the mechanical strength was better when using GA but the more toxic effect on dermal fibroblast makes EDC a more suitable crosslinker for future skin tissue engineering.
  3. Genotoxicity and cytotoxicity of ovine collagen on human dermal fibroblasts
    Busra FM, Chowdhury SR, Saim AB, Idrus RB
    Saudi Med J, 2011 Dec;32(12):1311-2.
    PMID: 22159390
  4. Fulltext Attachment, Proliferation, and Morphological Properties of Human Dermal Fibroblasts on Ovine Tendon Collagen Scaffolds: A Comparative Study
    Busra FM, Lokanathan Y, Nadzir MM, Saim A, Idrus RBH, Chowdhury SR
    Malays J Med Sci, 2017 Mar;24(2):33-43.
    PMID: 28894402 DOI: 10.21315/mjms2017.24.2.5
    INTRODUCTION: Collagen type I is widely used as a biomaterial for tissue-engineered substitutes. This study aimed to fabricate different three-dimensional (3D) scaffolds using ovine tendon collagen type I (OTC-I), and compare the attachment, proliferation and morphological features of human dermal fibroblasts (HDF) on the scaffolds.

    METHODS: This study was conducted between the years 2014 to 2016 at the Tissue Engineering Centre, UKM Medical Centre. OTC-I was extracted from ovine tendon, and fabricated into 3D scaffolds in the form of sponge, hydrogel and film. A polystyrene surface coated with OTC-I was used as the 2D culture condition. Genipin was used to crosslink the OTC-I. A non-coated polystyrene surface was used as a control. The mechanical strength of OTC-I scaffolds was evaluated. Attachment, proliferation and morphological features of HDF were assessed and compared between conditions.

    RESULTS: The mechanical strength of OTC-I sponge was significantly higher than that of the other scaffolds. OTC-I scaffolds and the coated surface significantly enhanced HDF attachment and proliferation compared to the control, but no differences were observed between the scaffolds and coated surface. In contrast, the morphological features of HDF including spreading, filopodia, lamellipodia and actin cytoskeletal formation differed between conditions.

    CONCLUSION: OTC-I can be moulded into various scaffolds that are biocompatible and thus could be suitable as scaffolds for developing tissue substitutes for clinical applications and in vitro tissue models. However, further study is required to determine the effect of morphological properties on the functional and molecular properties of HDF.

  5. Tissue-Engineered Skin Substitute Enhances Wound Healing after Radiation Therapy
    Busra MF, Chowdhury SR, bin Ismail F, bin Saim A, Idrus RB
    Adv Skin Wound Care, 2016 Mar;29(3):120-9.
    PMID: 26866868 DOI: 10.1097/01.ASW.0000480556.78111.e4
    OBJECTIVE: When given in conjunction with surgery for treating cancer, radiation therapy may result in impaired wound healing, which, in turn, could cause skin ulcers. In this study, bilayer and monolayer autologous skin substitutes were used to treat an irradiated wound.

    MATERIALS AND METHODS: A single dose of 30 Gy of linear electron beam radiation was applied to the hind limb of nude mice before creating the skin lesion (area of 78.6 mm). Monolayer tissue-engineered skin substitutes (MTESSs) were prepared by entrapping cultured keratinocytes in fibrin matrix, and bilayer tissue-engineered skin substitutes (BTESSs) were prepared by entrapping keratinocytes and fibroblasts in separate layers. Bilayer tissue-engineered skin substitute and MTESS were implanted to the wound area. Gross appearance and wound area were analyzed to evaluate wound healing efficiency. Skin regeneration and morphological appearance were observed via histological and electron microscopy. Protein expressions of transforming growth factor β1 (TGF-β1), platelet-derived growth factor BB (PDGF-BB), and vascular endothelial growth factor (VEGF) in skin regeneration were evaluated by immunohistochemistry (IHC).

    RESULTS: Macroscopic observation revealed that at day 13, treatments with BTESS completely healed the irradiated wound, whereas wound sizes of 1.1 ± 0.05 and 6.8 ± 0.14 mm were measured in the MTESS-treated and untreated control groups, respectively. Hematoxylin-eosin (H&E) analysis showed formation of compact and organized epidermal and dermal layers in the BTESS-treated group, as compared with MTESS-treated and untreated control groups. Ultrastructural analysis indicates maturation of skin in BTESS-treated wound evidenced by formation of intermediate filament bundles in the dermal layer and low intercellular space in the epidermal layer. Expressions of TGF-β1, PDGF-BB, and VEGF were also higher in BTESS-treated wounds, compared with MTESS-treated wounds.

    CONCLUSIONS: These results indicate that BTESS is the preferred treatment for irradiated wound ulcers.

  6. Fulltext MUSiC: a model-unspecific search for new physics in proton-proton collisions at s = 13 TeV
    CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(7):629.
    PMID: 34727144 DOI: 10.1140/epjc/s10052-021-09236-z
    Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 , are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.
  7. Fulltext Measurements of production cross sections of the Higgs boson in the four-lepton final state in proton-proton collisions at s = 13 TeV
    CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(6):488.
    PMID: 34727143 DOI: 10.1140/epjc/s10052-021-09200-x
    Production cross sections of the Higgs boson are measured in the H → Z Z → 4 ℓ ( ℓ = e , μ ) decay channel. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV , collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137 fb - 1 is used. The signal strength modifier μ , defined as the ratio of the Higgs boson production rate in the 4 ℓ channel to the standard model (SM) expectation, is measured to be μ = 0.94 ± 0.07 (stat) - 0.08 + 0.09 (syst) at a fixed value of m H = 125.38 GeV . The signal strength modifiers for the individual Higgs boson production modes are also reported. The inclusive fiducial cross section for the H → 4 ℓ process is measured to be 2 . 84 - 0.22 + 0.23 (stat) - 0.21 + 0.26 (syst) fb , which is compatible with the SM prediction of 2.84 ± 0.15 fb for the same fiducial region. Differential cross sections as a function of the transverse momentum and rapidity of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet are measured. A new set of cross section measurements in mutually exclusive categories targeted to identify production mechanisms and kinematical features of the events is presented. The results are in agreement with the SM predictions.
  8. Fulltext Search for direct pair production of supersymmetric partners to the τ lepton in proton-proton collisions at s = 13 TeV
    CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.
    Eur Phys J C Part Fields, 2020;80(3):189.
    PMID: 32226948 DOI: 10.1140/epjc/s10052-020-7739-7
    A search is presented for τ slepton pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV . The search is carried out in events containing two τ leptons in the final state, on the assumption that each τ slepton decays primarily to a τ lepton and a neutralino. Events are considered in which each τ lepton decays to one or more hadrons and a neutrino, or in which one of the τ leptons decays instead to an electron or a muon and two neutrinos. The data, collected with the CMS detector in 2016 and 2017, correspond to an integrated luminosity of 77.2 fb - 1 . The observed data are consistent with the standard model background expectation. The results are used to set 95% confidence level upper limits on the cross section for τ slepton pair production in various models for τ slepton masses between 90 and 200 GeV and neutralino masses of 1, 10, and 20 GeV . In the case of purely left-handed τ slepton production and decay to a τ lepton and a neutralino with a mass of 1 GeV , the strongest limit is obtained for a τ slepton mass of 125 GeV at a factor of 1.14 larger than the theoretical cross section.
  9. Identification of suitable culture condition for expansion and osteogenic differentiation of human bone marrow stem cells
    Chowdhury SR, Ng MH, Hassan NS, Aminuddin BS, Ruszymah BH
    Hum. Cell, 2012 Sep;25(3):69-77.
    PMID: 22968953
    This study was undertaken in order to identify the best culture strategy to expand and osteogenic differentiation of human bone marrow stem cells (hBMSCs) for subsequent bone tissue engineering. In this regard, the experiment was designed to evaluate whether it is feasible to bypass the expansion phase during hBMSCs differentiation towards osteogenic lineages by early induction, if not identification of suitable culture media for enhancement of hBMSCs expansion and osteogenic differentiation. It was found that introduction of osteogenic factors in alpha-minimum essential medium (αMEM) during expansion phase resulted in significant reduction of hBMSCs growth rate and osteogenic gene expressions. In an approach to identify suitable culture media, the growth and differentiation potential of hBMSCs were evaluated in αMEM, F12:DMEM (1:1; FD), and FD with growth factors. It was found that αMEM favors the expansion and osteogenic differentiation of hBMSCs compared to that in FD. However, supplementation of growth factors in FD, only during expansion phase, enhances the hBMSCs growth rate and significantly up-regulates the expression of CBFA-1 (the early markers of osteogenic differentiation) during expansion, and, other osteogenic genes at the end of induction compared to the cells in αMEM and FD. These results suggested that the expansion and differentiation phase of the hBMSCs should be separately and carefully timed. For bone tissue engineering, supplementation of growth factors in FD only during the expansion phase was sufficient to promote hBMSCs expansion and differentiation, and preferably the most efficient culture condition.
  10. One-Step Purification of Human Skeletal Muscle Myoblasts and Subsequent Expansion Using Laminin-Coated Surface
    Chowdhury SR, binti Ismail A, Chee SC, bin Laupa MS, binti Jaffri F, Saberi SE, et al.
    Tissue Eng Part C Methods, 2015 Nov;21(11):1135-42.
    PMID: 26061720 DOI: 10.1089/ten.TEC.2015.0015
    Skeletal myoblasts have been extensively used to study muscle growth and differentiation, and were recently tested for their application as cell therapy and as a gene delivery system to treat muscle and nonmuscle diseases. However, contamination of fibroblasts in isolated cells from skeletal muscle is one of the long-standing problems for routine expansion. This study aimed to establish a simple one-step process to purify myoblasts and maintain their purity during expansion. Mixed cells were preplated serially on laminin- and collagen type I-coated surfaces in a different array for 5, 10, and 15 min. Immunocytochemical staining with antibodies specific to myoblasts was performed to evaluate myoblast attachment efficiency, purity, and yield. It was found that laminin-coated surface favors the attachment of myoblasts. Highest myoblast purity of 78.9% ± 6.8% was achieved by 5 min of preplating only on the laminin-coated surface with a yield of 56.9% ± 3.3%. Primary cells, isolated from skeletal muscle (n = 4), confirm the enhancement of purity through preplating on laminin-coated surface for 5 min. Subsequent expansion after preplating enhanced myoblast purity due to an increase in myoblast growth than fibroblasts. Myoblast purity of ∼ 98% was achieved when another preplating was performed during passaging. In conclusion, myoblasts can be purified and efficiently expanded in one step by preplating on laminin-coated surface, which is a simple and robust technique.
  11. Collagen Type I: A Versatile Biomaterial
    Chowdhury SR, Mh Busra MF, Lokanathan Y, Ng MH, Law JX, Cletus UC, et al.
    Adv Exp Med Biol, 2018 10 26;1077:389-414.
    PMID: 30357700 DOI: 10.1007/978-981-13-0947-2_21
    Collagen type I is the most abundant matrix protein in the human body and is highly demanded in tissue engineering, regenerative medicine, and pharmaceutical applications. To meet the uprising demand in biomedical applications, collagen type I has been isolated from mammalians (bovine, porcine, goat and rat) and non-mammalians (fish, amphibian, and sea plant) source using various extraction techniques. Recent advancement enables fabrication of collagen scaffolds in multiple forms such as film, sponge, and hydrogel, with or without other biomaterials. The scaffolds are extensively used to develop tissue substitutes in regenerating or repairing diseased or damaged tissues. The 3D scaffolds are also used to develop in vitro model and as a vehicle for delivering drugs or active compounds.
  12. Effect of supplementation of dermal fibroblasts conditioned medium on expansion of keratinocytes through enhancing attachment
    Chowdhury SR, Aminuddin BS, Ruszymah BH
    Indian J Exp Biol, 2012 May;50(5):332-9.
    PMID: 22803323
    In the present study in vitro expansion of human keratinocytes by supplementing dermal fibroblasts conditioned medium (DFCM) has been reported. Effect of two different DFCM acquired by culturing fibroblasts in keratinocyte-specific medium (defined keratinocytes serum free medium, DFCM-DKSFM) and fibroblast-specific serum free medium (F12: DMEM nutrient mix, DFCM-FD) have been compared. Growth kinetics of keratinocytes in terms of efficiency of cell attachment, expansion index, apparent specific growth rate and growth potential at the end of culture was evaluated in culture supplemented with DFCM-DKSFM and DFCM-FD in comparison with control i.e. DKSFM only. Results indicated that supplementation of DFCM caused significant increase in keratinocyte attachment. Efficiency of keratinocyte attachment in culture supplemented with bFCM-DKSFM was significantly higher compared to those cultured in DFCM-FD and DKSFM. In addition, the expansion index of keratinocytes in cultures supplemented with DFCM-DKSFM and DFCM-FD were 3.7 and 2.2 times higher than that of control condition even though the apparent growth rate and proliferative potential was found significantly lower. These results suggested that supplementation of DFCM enhanced expansion of keratinocyte by increasing efficiency of cell attachment, and DFCM-DKSFM provided suitable condition for in vitro expansion of keratinocytes compared to DFCM-FD and control condition.
  13. Ovine tendon collagen: Extraction, characterisation and fabrication of thin films for tissue engineering applications
    Fauzi MB, Lokanathan Y, Aminuddin BS, Ruszymah BHI, Chowdhury SR
    Mater Sci Eng C Mater Biol Appl, 2016 Nov 01;68:163-171.
    PMID: 27524008 DOI: 10.1016/j.msec.2016.05.109
    Collagen is the most abundant extracellular matrix (ECM) protein in the human body, thus widely used in tissue engineering and subsequent clinical applications. This study aimed to extract collagen from ovine (Ovis aries) Achilles tendon (OTC), and to evaluate its physicochemical properties and its potential to fabricate thin film with collagen fibrils in a random or aligned orientation. Acid-solubilized protein was extracted from ovine Achilles tendon using 0.35M acetic acid, and 80% of extracted protein was measured as collagen. SDS-PAGE and mass spectrometry analysis revealed the presence of alpha 1 and alpha 2 chain of collagen type I (col I). Further analysis with Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS) confirms the presence of triple helix structure of col I, similar to commercially available rat tail col I. Drying the OTC solution at 37°C resulted in formation of a thin film with randomly orientated collagen fibrils (random collagen film; RCF). Introduction of unidirectional mechanical intervention using a platform rocker prior to drying facilitated the fabrication of a film with aligned orientation of collagen fibril (aligned collagen film; ACF). It was shown that both RCF and ACF significantly enhanced human dermal fibroblast (HDF) attachment and proliferation than that on plastic surface. Moreover, cells were distributed randomly on RCF, but aligned with the direction of mechanical intervention on ACF. In conclusion, ovine tendon could be an alternative source of col I to fabricate scaffold for tissue engineering applications.
  14. Cardiomyogenic differentiation of human sternal bone marrow mesenchymal stem cells using a combination of basic fibroblast growth factor and hydrocortisone
    Hafez P, Jose S, Chowdhury SR, Ng MH, Ruszymah BH, Abdul Rahman Mohd R
    Cell Biol Int, 2016 Jan;40(1):55-64.
    PMID: 26289249 DOI: 10.1002/cbin.10536
    The alarming rate of increase in myocardial infarction and marginal success in efforts to regenerate the damaged myocardium through conventional treatments creates an exceptional avenue for cell-based therapy. Adult bone marrow mesenchymal stem cells (MSCs) can be differentiated into cardiomyocytes, by treatment with 5-azacytidine, thus, have been anticipated as a therapeutic tool for myocardial infarction treatment. In this study, we investigated the ability of basic fibroblastic growth factor (bFGF) and hydrocortisone as a combined treatment to stimulate the differentiation of MSCs into cardiomyocytes. MSCs were isolated from sternal marrow of patients undergoing heart surgery (CABG). The isolated cells were initially monitored for the growth pattern, followed by characterization using ISCT recommendations. Cells were then differentiated using a combination of bFGF and hydrocortisone and evaluated for the expression of characteristic cardiac markers such as CTnI, CTnC, and Cnx43 at protein level using immunocytochemistry and flow cytometry, and CTnC and CTnT at mRNA level. The expression levels and pattern of the cardiac markers upon analysis with ICC and qRT-PCR were similar to that of 5-azacytidine induced cells and cultured primary human cardiomyocytes. However, flow cytometric evaluation revealed that induction with bFGF and hydrocortisone drives MSC differentiation to cardiomyocytes with a marginally higher efficiency. These results indicate that combination treatment of bFGF and hydrocortisone can be used as an alternative induction method for cardiomyogenic differentiation of MSCs for future clinical applications.
  15. Development of an In Vitro Cardiac Ischemic Model Using Primary Human Cardiomyocytes
    Hafez P, Chowdhury SR, Jose S, Law JX, Ruszymah BHI, Mohd Ramzisham AR, et al.
    Cardiovasc Eng Technol, 2018 09;9(3):529-538.
    PMID: 29948837 DOI: 10.1007/s13239-018-0368-8
    Developing experimental models to study ischemic heart disease is necessary for understanding of biological mechanisms to improve the therapeutic approaches for restoring cardiomyocytes function following injury. The aim of this study was to develop an in vitro hypoxic/re-oxygenation model of ischemia using primary human cardiomyocytes (HCM) and define subsequent cytotoxic effects. HCM were cultured in serum and glucose free medium in hypoxic condition with 1% O2 ranging from 30 min to 12 h. The optimal hypoxic exposure time was determined using Hypoxia Inducible Factor 1α (HIF-1α) as the hypoxic marker. Subsequently, the cells were moved to normoxic condition for 3, 6 and 9 h to replicate the re-oxygenation phase. Optimal period of hypoxic/re-oxygenation was determined based on 50% mitochondrial injury via 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay and cytotoxicity via lactate dehydrogenase (LDH) assay. It was found that the number of cells expressing HIF-1α increased with hypoxic time and 3 h was sufficient to stimulate the expression of this marker in all the cells. Upon re-oxygenation, mitochondrial activity reduced significantly whereas the cytotoxicity increased significantly with time. Six hours of re-oxygenation was optimal to induce reversible cell injury. The injury became irreversible after 9 h as indicated by > 60% LDH leakage compared to the control group cultured in normal condition. Under optimized hypoxic reoxygenation experimental conditions, mesenchymal stem cells formed nanotube with ischemic HCM and facilitated transfer of mitochondria suggesting the feasibility of using this as a model system to study molecular mechanisms of myocardial injury and rescue.
  16. Human Amniotic Membrane with Aligned Electrospun Fiber as Scaffold for Aligned Tissue Regeneration
    Hasmad H, Yusof MR, Mohd Razi ZR, Hj Idrus RB, Chowdhury SR
    Tissue Eng Part C Methods, 2018 06;24(6):368-378.
    PMID: 29690856 DOI: 10.1089/ten.TEC.2017.0447
    Fabrication of composite scaffolds is one of the strategies proposed to enhance the functionality of tissue-engineered scaffolds for improved tissue regeneration. By combining multiple elements together, unique biomimetic scaffolds with desirable physical and mechanical properties can be tailored for tissue-specific applications. Despite having a highly porous structure, the utility of electrospun fibers (EF) as scaffold is usually hampered by their insufficient mechanical strength. In this study, we attempted to produce a mechanically competent scaffold with cell-guiding ability by fabricating aligned poly lactic-co-glycolic acid (PLGA) fibers on decellularized human amniotic membrane (HAM), known to possess favorable tensile and wound healing properties. Decellularization of HAM in 18.75 μg/mL of thermolysin followed by a brief treatment in 0.25 M sodium hydroxide efficiently removed the amniotic epithelium and preserved the ultrastructure of the underlying extracellular matrix. The electrospinning of 20% (w/v) PLGA 50:50 polymer on HAM yielded beadless fibers with straight morphology. Subsequent physical characterization revealed that EF-HAM scaffold with a 3-min fabrication had the most aligned fibers with the lowest fiber diameter in comparison with EF-HAM 5- and 7-min scaffolds. Hydrated EF-HAM scaffolds with 3-min deposition had a greater tensile strength than the other scaffolds despite having thinner fibers. Nevertheless, wet HAM and EF-HAMs regardless of the fiber thicknesses had a significantly lower Young's modulus, and hence, a higher elasticity compared with dry HAM and EF-HAMs. Biocompatibility analysis showed that the viability and migration rate of skeletal muscle cells on EF-HAMs were similar to control and HAM alone. Skeletal muscle cells seeded on HAM were shown to display random orientation, whereas cells on EF-HAM scaffolds were oriented along the alignment of the electrospun PLGA fibers. In summary, besides having good mechanical strength and elasticity, EF-HAM scaffold design decorated with aligned fiber topography holds a promising potential for use in the development of aligned tissue constructs.
  17. Large-Scale Expansion of Human Mesenchymal Stem Cells
    Hassan MNFB, Yazid MD, Yunus MHM, Chowdhury SR, Lokanathan Y, Idrus RBH, et al.
    Stem Cells Int, 2020;2020:9529465.
    PMID: 32733574 DOI: 10.1155/2020/9529465
    Mesenchymal stem cells (MSCs) are multipotent stem cells with strong immunosuppressive property that renders them an attractive source of cells for cell therapy. MSCs have been studied in multiple clinical trials to treat liver diseases, peripheral nerve damage, graft-versus-host disease, autoimmune diseases, diabetes mellitus, and cardiovascular damage. Millions to hundred millions of MSCs are required per patient depending on the disease, route of administration, frequency of administration, and patient body weight. Multiple large-scale cell expansion strategies have been described in the literature to fetch the cell quantity required for the therapy. In this review, bioprocessing strategies for large-scale expansion of MSCs were systematically reviewed and discussed. The literature search in Medline and Scopus databases identified 26 articles that met the inclusion criteria and were included in this review. These articles described the large-scale expansion of 7 different sources of MSCs using 4 different bioprocessing strategies, i.e., bioreactor, spinner flask, roller bottle, and multilayered flask. The bioreactor, spinner flask, and multilayered flask were more commonly used to upscale the MSCs compared to the roller bottle. Generally, a higher expansion ratio was achieved with the bioreactor and multilayered flask. Importantly, regardless of the bioprocessing strategies, the expanded MSCs were able to maintain its phenotype and potency. In summary, the bioreactor, spinner flask, roller bottle, and multilayered flask can be used for large-scale expansion of MSCs without compromising the cell quality.
  18. Fulltext Measurement of the [Formula: see text] production cross section using events in the [Formula: see text] final state in pp collisions at [Formula: see text]
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2017;77(3):172.
    PMID: 28408859 DOI: 10.1140/epjc/s10052-017-4718-8
    The cross section of top quark-antiquark pair production in proton-proton collisions at [Formula: see text] is measured by the CMS experiment at the LHC, using data corresponding to an integrated luminosity of 2.2[Formula: see text]. The measurement is performed by analyzing events in which the final state includes one electron, one muon, and two or more jets, at least one of which is identified as originating from hadronization of a b quark. The measured cross section is [Formula: see text], in agreement with the expectation from the standard model.
  19. Fulltext Measurement of the production cross section of a W boson in association with two b jets in pp collisions at [Formula: see text]
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2017;77(2):92.
    PMID: 28331430 DOI: 10.1140/epjc/s10052-016-4573-z
    The production cross section of a W boson in association with two b jets is measured using a sample of proton-proton collisions at [Formula: see text] collected by the CMS experiment at the CERN LHC. The data sample corresponds to an integrated luminosity of 19.8[Formula: see text]. The W bosons are reconstructed via their leptonic decays, [Formula: see text], where [Formula: see text] or [Formula: see text]. The fiducial region studied contains exactly one lepton with transverse momentum [Formula: see text] and pseudorapidity [Formula: see text], with exactly two b jets with [Formula: see text] and [Formula: see text] and no other jets with [Formula: see text] and [Formula: see text]. The cross section is measured to be [Formula: see text]+[Formula: see text], in agreement with standard model predictions.
  20. Fulltext Measurements of the [Formula: see text] production cross section in lepton+jets final states in pp collisions at 8 [Formula: see text] and ratio of 8 to 7 [Formula: see text] cross sections
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2017;77(1):15.
    PMID: 28260978 DOI: 10.1140/epjc/s10052-016-4504-z
    A measurement of the top quark pair production ([Formula: see text]) cross section in proton-proton collisions at the centre-of-mass energy of 8[Formula: see text] is presented using data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 19.6[Formula: see text]. This analysis is performed in the [Formula: see text] decay channels with one isolated, high transverse momentum electron or muon and at least four jets, at least one of which is required to be identified as originating from hadronization of a b quark. The calibration of the jet energy scale and the efficiency of b jet identification are determined from data. The measured [Formula: see text] cross section is [Formula: see text]. This measurement is compared with an analysis of 7[Formula: see text] data, corresponding to an integrated luminosity of 5.0[Formula: see text], to determine the ratio of 8[Formula: see text] to 7[Formula: see text] cross sections, which is found to be [Formula: see text]. The measurements are in agreement with QCD predictions up to next-to-next-to-leading order.
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