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    Hydrogel Design and Development for Osteoarthritis Treatment

    , M.Sc. Thesis Sharif University of Technology Mirshafeeyan, Mahshad (Author) ; Yaghmaei, Soheyla (Supervisor) ; Mashayekhan, Shohreh (Supervisor)
    Abstract
    "osteoarthritis" is one of the most common joint diseases. This disease has a close relationship with factors such as aging, weight gain, genetics, mechanical pressures, and severe injuries. Although the mechanism of this disease is not fully understood, inflammation is one of the main causes of its exacerbation and progression. controlling inflammation can greatly help in controlling the disease. One of the common treatment methods for osteoarthritis is intra-articular injection of hyaluronic acid and triamcinolone as anti-inflammatory drug. Hyaluronic acid is the main component of synovial fluid, with its viscosupplementation property, prevents bones from rubbing against each other in the... 

    Developing Protein-Loaded Modified Hyaluronic Acid Hydrogel for Tissue Regeneration

    , M.Sc. Thesis Sharif University of Technology Asadi Korayem, Maryam (Author) ; Abdekhodaie, Mohammad Jafar (Supervisor)
    Abstract
    Growth factors play an important role in tissue repair and regeneration including articular cartilage tissue. Direct injection of growth factor is a common practice in clinics. However, it has been shown that this method is not very effective and, in some cases, induces some side effects. Moreover, incorporation of this valuable signals in systems where they are quickly released and washed out is not effective as well. Thereby the aim of this study was to design and fabricate an efficient system to effectively deliver growth factors for cartilage tissue engineering. The designed system is an injectable, in situ forming hydrogel, based on hyaluronic acid (HA) as a biocompatible and attractive... 

    Unraveling cancer metastatic cascade using microfluidics-based technologies

    , Article Biophysical Reviews ; Volume 14, Issue 2 , 2022 , Pages 517-543 ; 18672450 (ISSN) Hakim, M ; Kermanshah, L ; Abouali, H ; Hashemi, H. M ; Yari, A ; Khorasheh, F ; Alemzadeh, I ; Vossoughi, M ; Sharif University of Technology
    Springer Science and Business Media Deutschland GmbH  2022
    Abstract
    Cancer has long been a leading cause of death. The primary tumor, however, is not the main cause of death in more than 90% of cases. It is the complex process of metastasis that makes cancer deadly. The invasion metastasis cascade is the multi-step biological process of cancer cell dissemination to distant organ sites and adaptation to the new microenvironment site. Unraveling the metastasis process can provide great insight into cancer death prevention or even treatment. Microfluidics is a promising platform, that provides a wide range of applications in metastasis-related investigations. Cell culture microfluidic technologies for in vitro modeling of cancer tissues with fluid flow and the... 

    Poly-L-lysine/hyaluronan nanocarriers as a novel nanosystem for gene delivery

    , Article Journal of Microscopy ; Volume 287, Issue 1 , 2022 , Pages 32-44 ; 00222720 (ISSN) Souri, M ; Bagherzadeh, M. A ; Mofazzal Jahromi, M. A ; Mohammad-Beigi, H ; Abdoli, A ; Mir, H ; Roustazadeh, A ; Pirestani, M ; Sahandi Zangabad, P ; Kiani, J ; Bakhshayesh, A ; Jahani, M ; Joghataei, M. T ; Karimi, M ; Sharif University of Technology
    John Wiley and Sons Inc  2022
    Abstract
    The present research comes up with a novel DNA-loaded poly-L-lysine (PLL)/hyaluronan (HA) nanocarrier (DNA-loaded PLL/HA NCs) for gene delivery applications, as a promising candidate for gene delivery into diverse cells. A straightforward approach was employed to prepare such a nanosystem through masking DNA-loaded PLL molecules by HA. Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), field emission-scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) were used to analyse the interaction of the molecules as well as the physicochemical properties of the NCs. The NCs showed a negative charge of –24 ± 3 mV, with an average size of 138 ±... 

    Nano mesoporous silica for cancer treatment: ROS-responsive and redox-responsive carriers

    , Article Journal of Drug Delivery Science and Technology ; Volume 57 , 2020 Bahrami, F ; Abdekhodaie, M. J ; Behroozi, F ; Mehrvar, M ; Sharif University of Technology
    Editions de Sante  2020
    Abstract
    Reactive oxygen species ROS and redox agents are two features of cancer medium, which could be used through responsive drug delivery systems for cancer treatment. Furthermore, mesoporous silica nanoparticles (MSNs) have special characteristics to use them in ROS-responsive and redox-responsive carriers. To shed light on this issue, we propose two drug delivery systems: 1) responsive to hydrogen peroxide (a ROS component) and 2) responsive to dithiothreitol (a redox agent). The proposed carriers are composed of 4 parts: MSNs, responsive agent (selenocystine for ROS-responsive and dithiodipropionic for the redox-responsive carrier), hyaluronic acid as the coating and targeting agent, and the... 

    In situ forming interpenetrating hydrogels of hyaluronic acid hybridized with iron oxide nanoparticles

    , Article Biomaterials Science ; Volume 3, Issue 11 , Aug , 2015 , Pages 1466-1474 ; 20474830 (ISSN) Kheirabadi, M ; Shi, L ; Bagheri, R ; Kabiri, K ; Hilborn, J ; Ossipov, D. A ; Sharif University of Technology
    Royal Society of Chemistry  2015
    Abstract
    Four derivatives of hyaluronic acid (HA) bearing thiol (HA-SH), hydrazide (HA-hy), 2-dithiopyridyl (HA-SSPy), and aldehyde groups (HA-al) respectively were synthesized. Thiol and 2-dithiopyridyl as well as hydrazide and aldehyde make up two chemically orthogonal pairs of chemo-selective functionalities that allow in situ formation of interpenetrating (IPN) disulfide and hydrazone networks simultaneously upon the mixing of the above derivatives at once. The formation of IPN was demonstrated by comparing it with the formulations of the same total HA concentration but lacking one of the reactive components. The hydrogel composed of all four components was characterized by a larger elastic... 

    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
    Abstract
    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... 

    Gold nanorods for drug and gene delivery: An overview of recent advancements

    , Article Pharmaceutics ; Volume 14, Issue 3 , 2022 ; 19994923 (ISSN) Jahangiri Manesh, A ; Mousazadeh, M ; Taji, S ; Bahmani, A ; Zarepour, A ; Zarrabi, A ; Sharifi, E ; Azimzadeh, M ; Sharif University of Technology
    MDPI  2022
    Abstract
    Over the past few decades, gold nanomaterials have shown great promise in the field of nanotechnology, especially in medical and biological applications. They have become the most used nanomaterials in those fields due to their several advantageous. However, rod-shaped gold nanoparticles, or gold nanorods (GNRs), have some more unique physical, optical, and chemical properties, making them proper candidates for biomedical applications including drug/gene delivery, photothermal/photodynamic therapy, and theranostics. Most of their therapeutic applications are based on their ability for tunable heat generation upon exposure to near-infrared (NIR) radiation, which is helpful in both... 

    Folic acid-decorated PH-responsive nanoniosomes with enhanced endocytosis for breast cancer therapy: in vitro studies

    , Article Frontiers in Pharmacology ; Volume 13 , 2022 ; 16639812 (ISSN) Rezaei, T ; Rezaei, M ; Karimifard, S ; Mahmoudi Beram, F ; Dakkali, M. S ; Heydari, M ; Afshari Behbahanizadeh, S ; Mostafavi, E ; Bokov, D. O ; Ansari, M. J ; Farasati Far, B ; Akbarzadeh, I ; Chaiyasut, C ; Sharif University of Technology
    Frontiers Media S.A  2022
    Abstract
    Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women after lung cancer. The purpose of this study is a targeted delivery toward in vitro (on MCF7 and 4T1 breast cancer cell lines) through niosomes-based nanocarriers. To this end, different bioactive molecules, including hyaluronic acid (HA), folic acid (FA), and polyethylene glycol (PEG), were used and compared for surface modification of niosomes to enhance endocytosis. FA-functionalized niosomes (Nio/5-FU/FA) were able to increase cell cytotoxicity and reduce cell migration and invasion compared to PEG-functionalized niosomes (Nio/5-FU/PEG), and HA-functionalized niosomes... 

    Folate conjugated hyaluronic acid coated alginate nanogels encapsulated oxaliplatin enhance antitumor and apoptosis efficacy on colorectal cancer cells (HT29 cell line)

    , Article Toxicology in Vitro ; Volume 65 , 2020 Movahedi Shad, P ; Zare Karizi, S ; Safaie Javan, R ; Mirzaie, A ; Noorbazargan, H ; Akbarzadeh, I ; Rezaie, H ; Sharif University of Technology
    Elsevier Ltd  2020
    Abstract
    Oxaliplatin (OXA) has been widely used for treatment of colorectal cancer. In this study, to enhance antitumor and apoptosis efficacy, OXA was encapsulated in a novel folate conjugated hyaluronic acid coated alginate nanogels (F/HA/AL/OXA). The F/HA/AL/OXA nanogels were prepared by cross-linking process. The physico-chemical properties of F/HA/AL/OXA nanogels were characterized using scanning electron microscopy, transmission electron microscopy, fourier transform infrared spectroscopy, dynamic light scattering, and fluorescent spectrophotometry. The in-vitro antitumor activity of free OXA, AL, HA/AL, HA/AL/OXA and F/HA/AL/OXA nanogels were assessed using MTT assay against colorectal cancer... 

    Enzymatically crosslinked hyaluronic acid microgels as a vehicle for sustained delivery of cationic proteins

    , Article European Polymer Journal ; Volume 115 , 2019 , Pages 234-243 ; 00143057 (ISSN) Jooybar, E ; Abdekhodaie, M. J ; Mousavi, A ; Zoetebier, B ; Dijkstra, P. J ; Sharif University of Technology
    Elsevier Ltd  2019
    Abstract
    In this study, a novel biodegradable hyaluronic acid (HA) based microgel were prepared via enzymatic crosslinking of tyramine conjugated HA (HA-TA) in an inverse microemulsion. HA-TA microdroplets were crosslinked within a few seconds in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ). The high water content of the polymeric network and the inherent negative charge of the HA-TA microgels provided a suitable platform for encapsulation of cationic proteins like lysozyme and TGF-β1 growth factor. The results demonstrated that lysozyme was released, after an initial burst release, in a suitable sustained manner over a period of four weeks. Both diffusion and... 

    Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer

    , Article Materials Today Bio ; Volume 16 , 2022 ; 25900064 (ISSN) Mansoori Kermani, A ; Khalighi, S ; Akbarzadeh, I ; Niavol, F. R ; Motasadizadeh, H ; Mahdieh, A ; Jahed, V ; Abdinezhad, M ; Rahbariasr, N ; Hosseini, M ; Ahmadkhani, N ; Panahi, B ; Fatahi, Y ; Mozafari, M ; Kumar, A. P ; Mostafavi, E ; Sharif University of Technology
    Elsevier B.V  2022
    Abstract
    Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20%... 

    Developing hyaluronic acid microgels for sustained delivery of platelet lysate for tissue engineering applications

    , Article International Journal of Biological Macromolecules ; Volume 144 , 2020 , Pages 837-846 Jooybar, E ; Abdekhodaie, M. J ; Karperien, M ; Mousavi, A ; Alvi, M ; Dijkstra, P. J ; Sharif University of Technology
    Elsevier B.V  2020
    Abstract
    Platelet lysate (PL), a blood product that contains high concentrations of growth factors (GFs), can be considered as a cost-effective source of multiple GFs. In this study, hyaluronic acid (HA) based microgels were developed for delivery of PL proteins. Spherical microgel were prepared using a water in oil emulsion method. First, hyaluronic acid was grafted with tyramine groups, after which prepared microdroplets were crosslinked via an enzymatic reaction in the presence of hydrogen peroxide and horseradish peroxidase. Because of electrostatic interactions, these microgels are promising carriers for positively charged proteins entrapment like most of the GFs. When microgels are incubated in... 

    Combinatorial screening of nanoclay-reinforced hydrogels: a glimpse of the "holy grail" in orthopedic stem cell therapy?

    , Article ACS Applied Materials and Interfaces ; Volume 10, Issue 41 , 2018 , Pages 34924-34941 ; 19448244 (ISSN) Hasany, M ; Thakur, A ; Taebnia, N ; Kadumudi, F. B ; Shahbazi, M. A ; Pierchala, M. K ; Mohanty, S ; Orive, G ; Andresen, T. L ; Foldager, C. B ; Yaghmaei, S ; Arpanaei, A ; Gaharwar, A. K ; Mehrali, M ; Dolatshahi Pirouz, A ; Sharif University of Technology
    American Chemical Society  2018
    Abstract
    Despite the promise of hydrogel-based stem cell therapies in orthopedics, a significant need still exists for the development of injectable microenvironments capable of utilizing the regenerative potential of donor cells. Indeed, the quest for biomaterials that can direct stem cells into bone without the need of external factors has been the "Holy Grail" in orthopedic stem cell therapy for decades. To address this challenge, we have utilized a combinatorial approach to screen over 63 nanoengineered hydrogels made from alginate, hyaluronic acid, and two-dimensional nanoclays. Out of these combinations, we have identified a biomaterial that can promote osteogenesis in the absence of... 

    Brain-on-a-chip: Recent advances in design and techniques for microfluidic models of the brain in health and disease

    , Article Biomaterials ; Volume 285 , 2022 ; 01429612 (ISSN) Amirifar, L ; Shamloo, A ; Nasiri, R ; de Barros, N. R ; Wang, Z. Z ; Unluturk, B. D ; Libanori, A ; Ievglevskyi, O ; Diltemiz, S. E ; Sances, S ; Balasingham, I ; Seidlits, S. K ; Ashammakhi, N ; Sharif University of Technology
    Elsevier Ltd  2022
    Abstract
    Recent advances in biomaterials, microfabrication, microfluidics, and cell biology have led to the development of organ-on-a-chip devices that can reproduce key functions of various organs. Such platforms promise to provide novel insights into various physiological events, including mechanisms of disease, and evaluate the effects of external interventions, such as drug administration. The neuroscience field is expected to benefit greatly from these innovative tools. Conventional ex vivo studies of the nervous system have been limited by the inability of cell culture to adequately mimic in vivo physiology. While animal models can be used, their relevance to human physiology is uncertain and... 

    An injectable platelet lysate-hyaluronic acid hydrogel supports cellular activities and induces chondrogenesis of encapsulated mesenchymal stem cells

    , Article Acta Biomaterialia ; 2018 ; 17427061 (ISSN) Jooybar, E ; Abdekhodaie, M. J ; Alvi, M ; Mousavi, A ; Karperien, M ; Dijkstra, P. J ; Sharif University of Technology
    Acta Materialia Inc  2018
    Abstract
    Developing scaffolds that can provide cells and biological cues simultaneously in the defect site is of interest in tissue engineering field. In this study, platelet lysate (PL) as an autologous and inexpensive source of growth factors was incorporated into a cell-laden injectable hyaluronic acid-tyramine (HA-TA) hydrogel. Subsequently, the effect of platelet lysate on cell attachment, viability and differentiation of human mesenchymal stem cell (hMSCs) toward chondrocytes was investigated. HA-TA conjugates having a degree of substitution of 20 TA moieties per 100 disaccharide units were prepared and crosslinked in the presence of horseradish peroxidase and low concentrations of hydrogen...