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    Investigation of cancer response to chemotherapy: a hybrid multi-scale mathematical and computational model of the tumor microenvironment

    , Article Biomechanics and Modeling in Mechanobiology ; Volume 21, Issue 4 , 2022 , Pages 1233-1249 ; 16177959 (ISSN) Nikmaneshi, M. R ; Firoozabadi, B ; Sharif University of Technology
    Springer Science and Business Media Deutschland GmbH  2022
    Tumor microenvironment (TME) is a multi-scale biological environment that can control tumor dynamics with many biomechanical and biochemical factors. Investigating the physiology of TME with a heterogeneous structure and abnormal functions not only can achieve a deeper understanding of tumor behavior but also can help develop more efficient anti-cancer strategies. In this work, we develop a hybrid multi-scale mathematical model of TME to simulate the progression of a three-dimensional tumor and elucidate its response to different chemotherapy approaches. The chemotherapy approaches include multiple low dose (MLD) of anti-cancer drug, maximum tolerated dose (MTD) of anti-cancer drug,... 

    Experimental and Numerical Study of The Production of Alginate Microgels and Cancer Spheroids by Droplet-Based Microfluidic

    , M.Sc. Thesis Sharif University of Technology Rezaeian, Masoud (Author) ; Shamloo, Amir (Supervisor) ; Kazemzadeh Hannani, Siamak (Supervisor)
    Significant advances in biotechnology have led to the emergence of a cost-effective way with less ethical issues to study disease, organ functions, tumors, and their response to drugs besides studying on animals. Microfluidic devices and organ on a chip (tumor on a chip) were introduced to remove those obstacles. Organ on a chip is a powerful tool for studying different types of tissues and simulating diseases, especially cancers, for biological and medical applications. Organ (tumor) on a chip is considered as a smaller scale of the real organ or tumor and it causes to the real-time study of tissues and their functions more accurately. In this study, to fabricate a droplet-based... 

    Multi-scale Simulation of Tumor Microenvironment

    , M.Sc. Thesis Sharif University of Technology Nikmaneshi, Mohammad Reza (Author) ; Firoozabadi, Bahar (Supervisor) ; Mozafari, Ali Asghar (Co-Supervisor)
    Search for effective methods for treating cancer requires a deep understanding of the tumor microenvironment and its role in cancerous tumor growth and progression. Mathematical modeling methods, which have fewer limitations than experimental methods for examining the microcirculation of cancer in detail, are suggested to answer many questions about the behavior and dynamics of cancerous tumors. In the present study, a multi-scale mathematical model of the three-dimensional tumor microenvironment, including molecular, cellular, and tissue scales, is presented. In this model, important aspects of tumor microenvironmental dynamics including tumor growth, angiogenesis, cancer metabolism, and... 

    Simulation, Design, and Fabrication of a Droplet-Based Microfluidic Device to Study The Role of Tumor Microenvironment and Drug Effects on the Behavior of Multicellular Tumor Spheroids

    , Ph.D. Dissertation Sharif University of Technology Besanjideh, Mohsen (Author) ; Shamloo, Amir (Supervisor) ; Kazemzadeh Hannani, Siamak (Supervisor)
    Despite the extensive research conducted so far to treat cancer, this disease is still one of the main causes of death worldwide. The results of recent studies reveal the importance of the tumor microenvironment in the growth, proliferation, and invasion of the primary tumor. Most common models in cancer research, such as 2-dimensional in vitro models and xenografts, do not have sufficient ability to mimic the interaction of tumors with human stromal tissue. Therefore, the implementation of 3-dimensional in vitro models with the ability to replicate tumor microenvironments is essential. In this study, a microfluidic platform has been introduced to create parallel models of the tumor... 

    Neuronal cell navigation within a microfluidic device

    , Article Middle East Conference on Biomedical Engineering, MECBME ; 17-20 February , 2014 , pp. 261-264 Shamloo, A ; Sharif University of Technology
    In this study, the polarization and navigation of neuronal cells was studied in response to quantified gradients of nerve growth factor (NGF). To accomplish this, a microfluidic device was designed and fabricated to generate stable concentration gradients of biomolecules in a cell culture chamber within a 3D microenvironment. Numerical simulation was implemented to optimize the device geometry for generating a uniform concentration gradient of NGF which was found to remain stable for multiple hours. Neural Stem/ Progenitor Cell (NSCs) migration and differentiation was studied within this microfluidic device in response to NGF concentration and within a 3D environment of collagen matrix.... 

    Parallel in-vitro and in-vivo techniques for optimizing cellular microenvironments by implementing biochemical, biomechanical and electromagnetic stimulations

    , Article Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS ; 2012 , Pages 1397-1400 ; 1557170X (ISSN) ; 9781424441198 (ISBN) Shamloo, A ; Heibatollahi, M ; Ghafar Zadeh, E
    Development of novel engineering techniques that can promote new clinical treatments requires implementing multidisciplinary in-vitro and in-vivo approaches. In this study, we have implemented microfluidic devices and in-vivorat model to study the mechanism of neural stem cell migration and differentiation.These studies can result in the treatment of damages to the neuronal system. In this research, we have shown that by applying appropriate ranges of biochemical and biomechanical factors as well as by exposing the cells to electromagnetic fields, it is possible to improve viability, proliferation, directional migration and differentiation of neural stem cells. The results of this study can... 

    Microfluidic systems for stem cell-based neural tissue engineering

    , Article Lab on a Chip - Miniaturisation for Chemistry and Biology ; Volume 16, Issue 14 , 2016 , Pages 2551-2571 ; 14730197 (ISSN) Karimi, M ; Bahrami, S ; Mirshekari, H ; Moosavi Basri, S. M ; Bakhshian Nik, A ; Aref, A. R ; Akbari, M ; Hamblin, M. R ; Sharif University of Technology
    Royal Society of Chemistry  2016
    Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise... 

    Spheroids-on-a-chip: recent advances and design considerations in microfluidic platforms for spheroid formation and culture

    , Article Sensors and Actuators, B: Chemical ; Volume 263 , 15 June , 2018 , Pages 151-176 ; 09254005 (ISSN) Moshksayan, K ; Kashaninejad, N ; Ebrahimi Warkiani, M ; Lock, J. G ; Moghadas, H ; Firoozabadi, B ; Saidi, M. S ; Nguyen, N. T ; Sharif University of Technology
    Elsevier B.V  2018
    A cell spheroid is a three-dimensional (3D) aggregation of cells. Synthetic, in-vitro spheroids provide similar metabolism, proliferation, and species concentration gradients to those found in-vivo. For instance, cancer cell spheroids have been demonstrated to mimic in-vivo tumor microenvironments, and are thus suitable for in-vitro drug screening. The first part of this paper discusses the latest microfluidic designs for spheroid formation and culture, comparing their strategies and efficacy. The most recent microfluidic techniques for spheroid formation utilize emulsion, microwells, U-shaped microstructures, or digital microfluidics. The engineering aspects underpinning spheroid formation... 

    Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors

    , Article Scientific Reports ; Volume 12, Issue 1 , 2022 ; 20452322 (ISSN) Boroumand, A ; Mehrarya, M ; Ghanbarzadeh Dagheyan, A ; Ahmadian, M. T ; Sharif University of Technology
    Nature Research  2022
    Central Nervous System (CNS) malignant tumors are a leading cause of death worldwide with a high mortality rate. While numerous strategies have been proposed to treat CNS tumors, the treatment efficacy is still low mainly due to the existence of the Blood–Brain Barrier (BBB). BBB is a natural cellular layer between the circulatory system and brain extracellular fluid, limiting the transfer of drug particles and confining the routine treatment strategies in which drugs are released in the blood. Consequently, direct drug delivery methods have been devised to bypass the BBB. However, the efficiency of these methods is not enough to treat deep and large brain tumors. In the study at hand, the... 

    Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering

    , Article Journal of Biotechnology ; Volume 212 , 2015 , Pages 71-89 ; 01681656 (ISSN) Shamloo, A ; Mohammadaliha, N ; Mohseni, M ; Sharif University of Technology
    Elsevier  2015
    This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal... 

    Graphene aerogel nanoparticles for in-situ loading/pH sensitive releasing anticancer drugs

    , Article Colloids and Surfaces B: Biointerfaces ; Volume 186 , 2020 Ayazi, H ; Akhavan, O ; Raoufi, M ; Varshochian, R ; Hosseini Motlagh, N. S ; Atyabi, F ; Sharif University of Technology
    Elsevier B.V  2020
    Free polymer graphene aerogel nanoparticles (GA NPs) were synthesized by using reduction/aggregation of graphene oxide (GO) sheets in the presence of vitamin C (as a biocompatible reductant agent) at a low temperature (40 °C), followed by an effective sonication. Synthesis of GA NPs in doxorubicin hydrochloride (DOX)-containing solution results in the simultaneous synthesis and drug loading with higher performance (than that of the separately synthesized and loaded samples). To investigate the mechanism of loading and the capability of GA NPs in the loading of other drug structures, two groups of ionized (DOX, Amikacin sulfate and, D-glucosamine hydrochloride) and non-ionized (Paclitaxel... 

    Organ-tumor-on-a-chip for chemosensitivity assay: A critical review

    , Article Micromachines ; Volume 7, Issue 8 , 2016 ; 2072666X (ISSN) Kashaninejad, N ; Nikmaneshi, M. R ; Moghadas, H ; Kiyoumarsi Oskouei, A ; Rismanian, M ; Barisam, M ; Saidi, M. S ; Firoozabadi, B ; Sharif University of Technology
    MDPI AG  2016
    With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D) nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate... 

    Three-dimensional modeling of avascular tumor growth in both static and dynamic culture platforms

    , Article Micromachines ; Volume 10, Issue 9 , 2019 ; 2072666X (ISSN) Taghibakhshi, A ; Barisam, M ; Saidi, M. S ; Kashaninejad, N ; Nguyen, N. T ; Sharif University of Technology
    MDPI AG  2019
    Microfluidic cell culture platforms are ideal candidates for modeling the native tumor microenvironment because they can precisely reconstruct in vivo cellular behavior. Moreover, mathematical modeling of tumor growth can pave the way toward description and prediction of growth pattern as well as improving cancer treatment. In this study, a modified mathematical model based on concentration distribution is applied to tumor growth in both conventional static culture and dynamic microfluidic cell culture systems. Apoptosis and necrosis mechanisms are considered as the main inhibitory factors in the model, while tumor growth rate and nutrient consumption rate are modified in both quiescent and... 

    A multi-scale model for determining the effects of pathophysiology and metabolic disorders on tumor growth

    , Article Scientific Reports ; Volume 10, Issue 1 , 20 February , 2020 Nikmaneshi, M. R ; Firoozabadi, B ; Mozafari, A ; Munn, L. L ; Sharif University of Technology
    Nature Research  2020
    The search for efficient chemotherapy drugs and other anti-cancer treatments would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. Because in vivo experimental methods are unable to isolate or control individual factors of the TME and in vitro models often do not include all the contributing factors, some questions are best addressed with systems biology mathematical models. In this work, we present a new fully-coupled, agent-based, multi-scale mathematical model of tumor growth, angiogenesis and metabolism that includes important aspects of the TME spanning subcellular-, cellular- and tissue-level scales. The mathematical model is... 

    Virotheranostics, a double-barreled viral gun pointed toward cancer; Ready to shoot?

    , Article Cancer Cell International ; Volume 20, Issue 1 , 2020 Keshavarz, M ; Sabbaghi, A ; Miri, S. M ; Rezaeyan, A ; Arjeini, Y ; Ghaemi, A ; Sharif University of Technology
    BioMed Central Ltd  2020
    Compared with conventional cancer treatments, the main advantage of oncolytic virotherapy is its tumor-selective replication followed by the destruction of malignant cells without damaging healthy cells. Accordingly, this kind of biological therapy can potentially be used as a promising approach in the field of cancer management. Given the failure of traditional monitoring strategies (such as immunohistochemical analysis (in providing sufficient safety and efficacy necessary for virotherapy and continual pharmacologic monitoring to track pharmacokinetics in real-time, the development of alternative strategies for ongoing monitoring of oncolytic treatment in a live animal model seems... 

    Chemo-mechanistic multi-scale model of a three-dimensional tumor microenvironment to quantify the chemotherapy response of cancer

    , Article Biotechnology and Bioengineering ; Volume 118, Issue 10 , 2021 , Pages 3871-3887 ; 00063592 (ISSN) Nikmaneshi, M. R ; Firoozabadi, B ; Mozafari, A ; Sharif University of Technology
    John Wiley and Sons Inc  2021
    Exploring efficient chemotherapy would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. As in vivo experimental methods are unable to isolate or control individual factors of the TME, and in vitro models often cannot include all the contributing factors, some questions are best addressed with mathematical models of systems biology. In this study, we establish a multi-scale mathematical model of the TME to simulate three-dimensional tumor growth and angiogenesis and then implement the model for an array of chemotherapy approaches to elucidate the effect of TME conditions and drug scheduling on controlling tumor progression. The... 

    Targeted nanomedicines for the treatment of bone disease and regeneration

    , Article Medicinal Research Reviews ; Volume 41, Issue 3 , 2021 , Pages 1221-1254 ; 01986325 (ISSN) Ordikhani, F ; Zandi, N ; Mazaheri, M ; Luther, G. A ; Ghovvati, M ; Akbarzadeh, A ; Annabi, N ; Sharif University of Technology
    John Wiley and Sons Inc  2021
    Targeted delivery by either passive or active targeting of therapeutics to the bone is an attractive treatment for various bone related diseases such as osteoporosis, osteosarcoma, multiple myeloma, and metastatic bone tumors. Engineering novel drug delivery carriers can increase therapeutic efficacy and minimize the risk of side effects. Developmnet of nanocarrier delivery systems is an interesting field of ongoing studies with opportunities to provide more effective therapies. In addition, preclinical nanomedicine research can open new opportunities for preclinical bone-targeted drug delivery; nevertheless, further research is needed to progress these therapies towards clinical... 

    Immunomodulating hydrogels as stealth platform for drug delivery applications

    , Article Pharmaceutics ; Volume 14, Issue 10 , 2022 ; 19994923 (ISSN) Rezaei, Z ; Yilmaz Aykut, D ; Tourk, F. M ; Bassous, N ; Barroso Zuppa, M ; Shawl, A. I ; Ashraf, S. S ; Avci, H ; Hassan, S ; Sharif University of Technology
    MDPI  2022
    Non-targeted persistent immune activation or suppression by different drug delivery platforms can cause adverse and chronic physiological effects including cancer and arthritis. Therefore, non-toxic materials that do not trigger an immunogenic response during delivery are crucial for safe and effective in vivo treatment. Hydrogels are excellent candidates that can be engineered to control immune responses by modulating biomolecule release/adsorption, improving regeneration of lymphoid tissues, and enhancing function during antigen presentation. This review discusses the aspects of hydrogel-based systems used as drug delivery platforms for various diseases. A detailed investigation on... 

    A microfabricated platform for the study of chondrogenesis under different compressive loads

    , Article Journal of the Mechanical Behavior of Biomedical Materials ; Volume 78 , 2018 , Pages 404-413 ; 17516161 (ISSN) Kowsari Esfahan, R ; Jahanbakhsh, A ; Saidi, M. S ; Bonakdar, S ; Sharif University of Technology
    Elsevier Ltd  2018
    Microfluidic devices are beneficial in miniaturizing and multiplexing various cellular assays in a single platform. Chondrogenesis is known to pertain to chemical, topographical, and mechanical cues in the microenvironment. Mechanical cues themselves have numerous parameters such as strain magnitude, frequency, and stimulation time. Effects of different strain magnitudes on the chondrogenic differentiation of adult stem cells have not been explored thoroughly. Here, a new multilayer microdevice is presented for the unidirectional compressive stimulation of cells in a three-dimensional cell culture. Numerical simulations were performed to evaluate and optimize the design. Results showed a... 

    Oncolytic newcastle disease virus delivered by mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment

    , Article Virology Journal ; Volume 17, Issue 1 , 2020 Keshavarz, M ; Ebrahimzadeh, M. S ; Miri, S. M ; Dianat Moghadam, H ; Ghorbanhosseini, S. S ; Mohebbi, S. R ; Keyvani, H ; Ghaemi, A ; Sharif University of Technology
    BioMed Central Ltd  2020
    Background: Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. Methods: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune...