Publications by authors named "Anwarul Hasan"

116 Publications

Sulfated alginate/polycaprolactone double-emulsion nanoparticles for enhanced delivery of heparin-binding growth factors in wound healing applications.

Colloids Surf B Biointerfaces 2021 Sep 15;208:112105. Epub 2021 Sep 15.

Biomedical Engineering Program, Maroun Semaan Faculty of Engineering and Architecture, American University of Beirut, Beirut 1107 2020, Lebanon. Electronic address:

Diabetic foot ulcers (DFUs) that are not effectively treated could lead to partial or complete lower limb amputations. The lack of connective tissue growth factor (CTGF) and insulin-like growth factor (IGF-I) in DFUs results in limited matrix deposition and poor tissue repair. To enhance growth factor (GF) availability in DFUs, heparin (HN)-mimetic alginate sulfate/polycaprolactone (AlgSulf/PCL) double emulsion nanoparticles (NPs) with high affinity and sustained release of CTGF and IGF-I were synthesized. The NPs size, encapsulation efficiency (EE), cytotoxicity, cellular uptake and wound healing capacity in immortalized primary human adult epidermal cells (HaCaT) were assessed. The sonication time and amplitude used for NPs synthesis enabled the production of particles with a minimum of 236 ± 25 nm diameter. Treatment of HaCaT cells with up to 50 μg mL of NPs showed no cytotoxic effects after 72 h. The highest bovine serum albumin EE (94.6 %, P = 0.028) and lowest burst release were attained with AlgSulf/PCL. Moreover, cells treated with AlgSulf/CTGF (250 ng mL) exhibited the most rapid wound closure compared to controls while maintaining fibronectin synthesis. Double-emulsion NPs based on HN-mimetic AlgSulf represent a novel approach which can significantly enhance diabetic wound healing and can be expanded for applications requiring the delivery of other HN-binding GFs.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112105DOI Listing
September 2021

Diagnostic and drug release systems based on microneedle arrays in breast cancer therapy.

J Control Release 2021 Aug 21;338:341-357. Epub 2021 Aug 21.

Laboratory Experimental Oncology, Department of Pathology, Erasmus MC, 3015GD Rotterdam, the Netherlands. Electronic address:

Microneedle arrays have recently received much attention as cancer detection and treatment platforms, because invasive injections and detection of the biopsy are not needed, and drug metabolism by the liver, as well as adverse effects of systemic drug administration, are diminished. Microneedles have been used for diagnosis, vaccination, and in targeted drug delivery of breast cancer. In this review, we summarize the recent progress in diagnosis and targeted drug delivery for breast cancer treatment, using microneedle arrays to deliver active molecules through the skin. The results not only suggest that health and well-being of patients are improved, but also that microneedle arrays can deliver anticancer compounds in a relatively noninvasive manner, based on body weight, breast tumor size, and circulation time of the drug. Moreover, microneedles could allow simultaneous loading of multiple drugs and enable controlled release, thus effectively optimizing or preventing drug-drug interactions. This review is designed to encourage the use of microneedles for diagnosis and treatment of breast cancer, by describing general properties of microneedles, materials used for construction, mechanism of action, and principal benefits. Ongoing challenges and future perspectives for the application of microneedle array systems in breast cancer detection and treatment are highlighted.
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http://dx.doi.org/10.1016/j.jconrel.2021.08.036DOI Listing
August 2021

An engineered microfluidic blood-brain barrier model to evaluate the anti-metastatic activity of β-boswellic acid.

Biotechnol J 2021 Jul 27:e2100044. Epub 2021 Jul 27.

Laboratory for Stem Cell & Regenerative Medicine, Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Oman.

Background: The development of anti-cancer drugs with the ability to inhibit brain metastasis through the blood-brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models.

Main Methods: In this study, the Geltrex-based Transwell and microfluidic BBB models were applied to screen the effect of β-boswellic acid (β-BA) on the metastasis of MDA-MB-231 cells through the BBB in static and dynamic conditions, respectively.

Major Results: The toxicity assay revealed that β-BA deteriorates MDA-MB-231 cells, while β-BA had no detectable toxic effects on human umbilical vein endothelial cells (HUVECs) and astrocytes. Trans-endothelial electrical resistance evaluation showed sustainable barrier integrity upon treatment with β-BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of β-BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. β-BA significantly inhibited metastasis by 85%, while cisplatin (Cis), a positive control, inhibited cancer cell migration by 12% under static conditions. Upon applying a dynamic BBB model, it was revealed that β-BA-mediated metastasis inhibition was significantly higher than that mediated by Cis.

Conclusions And Implications:  In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models.

Graphical Abstract And Lay Summary: The development of anti-cancer drugs with the ability to inhibit brain metastasis through the blood-brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models. In this study, the Geltrex-based Transwell and microfluidic BBB models were applied to screen the effect of β-boswellic acid (β-BA) on the metastasis of MDA-MB-231 cells through the BBB in static and dynamic conditions, respectively. In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models.
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http://dx.doi.org/10.1002/biot.202100044DOI Listing
July 2021

Current progress in chimeric antigen receptor T cell therapy for glioblastoma multiforme.

Cancer Med 2021 Aug 19;10(15):5019-5030. Epub 2021 Jun 19.

Institute of Translational Pharmacology-CNR, Rome, Italy.

Glioblastoma multiforme (GBM) is one of the deadliest brain tumors with an unfavorable prognosis and overall survival of approximately 20 months following diagnosis. The current treatment for GBM includes surgical resections and chemo- and radiotherapeutic modalities, which are not effective. CAR-T immunotherapy has been proven effective for CD19-positive blood malignancies, and the application of CAR-T cell therapy for solid tumors including GBM offers great hope for this aggressive tumor which has a limited response to current treatments. CAR-T technology depends on the use of patient-specific T cells genetically engineered to express specific tumor-associated antigens (TAAs). Interaction of CAR-T cells with tumor cells triggers the destruction/elimination of these cells by the induction of cytotoxicity and the release of different cytokines. Despite the great promise of CAR-T cell-based therapy several challenges exist. These include the heterogeneity of GBM cancer cells, aberrant various signaling pathways involved in tumor progression, antigen escape, the hostile inhibitory GBM microenvironment, T cell dysfunction, blood-brain barrier, and defective antigen presentation. All need to be addressed before full application at the clinical level can begin. Herein we provide a focused review of the rationale for the use of different types of CAR-T cells (including FcγRs), the different GBM-associated antigens, the challenges still facing CAR-T-based therapy, and means to overcome such challenges. Finally, we enumerate currently completed and ongoing clinical trials, highlighting the different ways such trials are designed to overcome specific problems. Exploitation of the full potential of CAR-T cell therapy for GBM depends on their solution.
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http://dx.doi.org/10.1002/cam4.4064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335808PMC
August 2021

Imaging cancer cells with nanostructures: Prospects of nanotechnology driven non-invasive cancer diagnosis.

Adv Colloid Interface Sci 2021 Aug 3;294:102457. Epub 2021 Jun 3.

Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA 94304, USA.

The application of nanostructured materials in medicine is a rapidly evolving area of research that includes both the diagnosis and treatment of various diseases. Metals, metal oxides and carbon-based nanomaterials have shown much promise in medical technological advancements due to their tunable physical, chemical and biological properties. The nanoscale properties, especially the size, shape, surface chemistry and stability makes them highly desirable for diagnosing and treating various diseases, including cancers. Major applications of nanomaterials in cancer diagnosis include in vivo bioimaging and molecular marker detection, mainly as image contrast agents using modalities such as radio, magnetic resonance, and ultrasound imaging. When a suitable targeting ligand is attached on the nanomaterial surface, it can help pinpoint the disease site during imaging. The application of nanostructured materials in cancer diagnosis can help in the early detection, treatment and patient follow-up . This review aims to gather and present the information regarding the application of nanotechnology in cancer diagnosis. We also discuss the challenges and prospects regarding the application of nanomaterials as cancer diagnostic tools.
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http://dx.doi.org/10.1016/j.cis.2021.102457DOI Listing
August 2021

Development of Biopolymeric Hybrid Scaffold-Based on AAc/GO/nHAp/TiO Nanocomposite for Bone Tissue Engineering: In-Vitro Analysis.

Nanomaterials (Basel) 2021 May 17;11(5). Epub 2021 May 17.

Department of Biology, College of Sciences, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia.

Bone tissue engineering is an advanced field for treatment of fractured bones to restore/regulate biological functions. Biopolymeric/bioceramic-based hybrid nanocomposite scaffolds are potential biomaterials for bone tissue because of biodegradable and biocompatible characteristics. We report synthesis of nanocomposite based on acrylic acid (AAc)/guar gum (GG), nano-hydroxyapatite (HAp NPs), titanium nanoparticles (TiO NPs), and optimum graphene oxide (GO) amount via free radical polymerization method. Porous scaffolds were fabricated through freeze-drying technique and coated with silver sulphadiazine. Different techniques were used to investigate functional group, crystal structural properties, morphology/elemental properties, porosity, and mechanical properties of fabricated scaffolds. Results show that increasing amount of TiO in combination with optimized GO has improved physicochemical and microstructural properties, mechanical properties (compressive strength (2.96 to 13.31 MPa) and Young's modulus (39.56 to 300.81 MPa)), and porous properties (pore size (256.11 to 107.42 μm) and porosity (79.97 to 44.32%)). After 150 min, silver sulfadiazine release was found to be ~94.1%. In vitro assay of scaffolds also exhibited promising results against mouse pre-osteoblast () cell lines. Hence, these fabricated scaffolds would be potential biomaterials for bone tissue engineering in biomedical engineering.
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http://dx.doi.org/10.3390/nano11051319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156135PMC
May 2021

Development of nitric oxide releasing visible light crosslinked gelatin methacrylate hydrogel for rapid closure of diabetic wounds.

Biomed Pharmacother 2021 Aug 25;140:111747. Epub 2021 May 25.

Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar; Biomedical Research Center (BRC), Qatar University, Doha 2713, Qatar. Electronic address:

Management of non-healing and slow to heal diabetic wounds is a major concern in healthcare across the world. Numerous techniques have been investigated to solve the issue of delayed wound healing, though, mostly unable to promote complete healing of diabetic wounds due to the lack of proper cell proliferation, poor cell-cell communication, and higher chances of wound infections. These challenges can be minimized by using hydrogel based wound healing patches loaded with bioactive agents. Gelatin methacrylate (GelMA) has been proven to be a highly cell friendly, cell adhesive, and inexpensive biopolymer for various tissue engineering and wound healing applications. In this study, S-Nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, was incorporated in a highly porous GelMA hydrogel patch to improve cell proliferation, facilitate rapid cell migration, and enhance diabetic wound healing. We adopted a visible light crosslinking method to fabricate this highly porous biodegradable but relatively stable patch. Developed patches were characterized for morphology, NO release, cell proliferation and migration, and diabetic wound healing in a rat model. The obtained results indicate that SNAP loaded visible light crosslinked GelMA hydrogel patches can be highly effective in promoting diabetic wound healing.
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http://dx.doi.org/10.1016/j.biopha.2021.111747DOI Listing
August 2021

Magnetic nanocatalysts as multifunctional platforms in cancer therapy through the synthesis of anticancer drugs and facilitated Fenton reaction.

J Adv Res 2021 05 5;30:171-184. Epub 2020 Dec 5.

Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Background: Heterocyclic compounds have always been used as a core portion in the development of anticancer drugs. However, there is a pressing need for developing inexpensive and simple alternatives to high-cost and complex chemical agents-based catalysts for large-scale production of heterocyclic compounds. Also, development of some smart platforms for cancer treatment based on nanoparticles (NPs) which facilitate Fenton reaction have been widely explored by different scientists. Magnetic NPs not only can serve as catalysts in the synthesis of heterocyclic compounds with potential anticancer properties, but also are widely used as smart agents in targeting cancer cells and inducing Fenton reactions.

Aim Of Review: Therefore, in this review we aim to present an updated summary of the reports related to the main clinical or basic application and research progress of magnetic NPs in cancer as well as their application in the synthesis of heterocyclic compounds as potential anticancer drugs. Afterwards, specific tumor microenvironment (TME)-responsive magnetic nanocatalysts for cancer treatment through triggering Fenton-like reactions were surveyed. Finally, some ignored factors in the design of magnetic nanocatalysts- triggered Fenton-like reaction, challenges and future perspective of magnetic nanocatalysts-assisted synthesis of heterocyclic compounds and selective cancer therapy were discussed.This review may pave the way for well-organized translation of magnetic nanocatalysts in cancer therapy from the bench to the bedside.
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http://dx.doi.org/10.1016/j.jare.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132204PMC
May 2021

Bioengineered microfluidic blood-brain barrier models in oncology research.

Transl Oncol 2021 Jul 14;14(7):101087. Epub 2021 Apr 14.

Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, 2713 Doha, Qatar; Biomedical Research Center (BRC), Qatar University, PO Box 2713 Doha, Qatar. Electronic address:

Metastasis is the major reason for most brain tumors with up to a 50% chance of occurrence in patients with other types of malignancies. Brain metastasis occurs if cancer cells succeed to cross the 'blood-brain barrier' (BBB). Moreover, changes in the structure and function of BBB can lead to the onset and progression of diseases including neurological disorders and brain-metastases. Generating BBB models with structural and functional features of intact BBB is highly important to better understand the molecular mechanism of such ailments and finding novel therapeutic agents targeting them. Hence, researchers are developing novel in vitro BBB platforms that can recapitulate the structural and functional characteristics of BBB. Brain endothelial cells-based in vitro BBB models have thus been developed to investigate the mechanism of brain metastasis through BBB and facilitate the testing of brain targeted anticancer drugs. Bioengineered constructs integrated with microfluidic platforms are vital tools for recapitulating the features of BBB in vitro closely as possible. In this review, we outline the fundamentals of BBB biology, recent developments in the microfluidic BBB platforms, and provide a concise discussion of diverse types of bioengineered BBB models with an emphasis on the application of them in brain metastasis and cancer research in general. We also provide insights into the challenges and prospects of the current bioengineered microfluidic platforms in cancer research.
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http://dx.doi.org/10.1016/j.tranon.2021.101087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066424PMC
July 2021

3D bioprinting of engineered breast cancer constructs for personalized and targeted cancer therapy.

J Control Release 2021 05 25;333:91-106. Epub 2021 Mar 25.

Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Electronic address:

The bioprinting technique with specialized tissue production allows the study of biological, physiological, and behavioral changes of cancerous and non-cancerous tissues in response to pharmacological compounds in personalized medicine. To this end, to evaluate the efficacy of anticancer drugs before entering the clinical setting, tissue engineered 3D scaffolds containing breast cancer and derived from the especially patient, similar to the original tissue architecture, can potentially be used. Despite recent advances in the manufacturing of 3D bioprinted breast cancer tissue (BCT), many studies still suffer from reproducibility primarily because of the uncertainty of the materials used in the scaffolds and lack of printing methods. In this review, we present an overview of the breast cancer environment to optimize personalized treatment by examining and identifying the physiological and biological factors that mimic BCT. We also surveyed the materials and techniques related to 3D bioprinting, i.e, 3D bioprinting systems, current strategies for fabrication of 3D bioprinting tissues, cell adhesion and migration in 3D bioprinted BCT, and 3D bioprinted breast cancer metastasis models. Finally, we emphasized on the prospective future applications of 3D bioprinted cancer models for rapid and accurate drug screening in breast cancer.
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http://dx.doi.org/10.1016/j.jconrel.2021.03.026DOI Listing
May 2021

Stem cell-based approaches in cardiac tissue engineering: controlling the microenvironment for autologous cells.

Biomed Pharmacother 2021 Jun 23;138:111425. Epub 2021 Mar 23.

Department of Cardiovascular and Transplantation Surgery, Regional Central Hospital of Nancy, Lorraine University, Nancy 54500, France.

Cardiovascular disease is one of the leading causes of mortality worldwide. Cardiac tissue engineering strategies focusing on biomaterial scaffolds incorporating cells and growth factors are emerging as highly promising for cardiac repair and regeneration. The use of stem cells within cardiac microengineered tissue constructs present an inherent ability to differentiate into cell types of the human heart. Stem cells derived from various tissues including bone marrow, dental pulp, adipose tissue and umbilical cord can be used for this purpose. Approaches ranging from stem cell injections, stem cell spheroids, cell encapsulation in a suitable hydrogel, use of prefabricated scaffold and bioprinting technology are at the forefront in the field of cardiac tissue engineering. The stem cell microenvironment plays a key role in the maintenance of stemness and/or differentiation into cardiac specific lineages. This review provides a detailed overview of the recent advances in microengineering of autologous stem cell-based tissue engineering platforms for the repair of damaged cardiac tissue. A particular emphasis is given to the roles played by the extracellular matrix (ECM) in regulating the physiological response of stem cells within cardiac tissue engineering platforms.
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http://dx.doi.org/10.1016/j.biopha.2021.111425DOI Listing
June 2021

Stem cells based in vitro models: trends and prospects in biomaterials cytotoxicity studies.

Biomed Mater 2021 Mar 9;16(4):042003. Epub 2021 Mar 9.

Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad 38000 Punjab, Pakistan.

Advanced biomaterials are increasingly used for numerous medical applications from the delivery of cancer-targeted therapeutics to the treatment of cardiovascular diseases. The issues of foreign body reactions induced by biomaterials must be controlled for preventing treatment failure. Therefore, it is important to assess the biocompatibility and cytotoxicity of biomaterials on cell culture systems before proceeding to in vivo studies in animal models and subsequent clinical trials. Direct use of biomaterials on animals create technical challenges and ethical issues and therefore, the use of non-animal models such as stem cell cultures could be useful for determination of their safety. However, failure to recapitulate the complex in vivo microenvironment have largely restricted stem cell cultures for testing the cytotoxicity of biomaterials. Nevertheless, properties of stem cells such as their self-renewal and ability to differentiate into various cell lineages make them an ideal candidate for in vitro screening studies. Furthermore, the application of stem cells in biomaterials screening studies may overcome the challenges associated with the inability to develop a complex heterogeneous tissue using primary cells. Currently, embryonic stem cells, adult stem cells, and induced pluripotent stem cells are being used as in vitro preliminary biomaterials testing models with demonstrated advantages over mature primary cell or cell line based in vitro models. This review discusses the status and future directions of in vitro stem cell-based cultures and their derivatives such as spheroids and organoids for the screening of their safety before their application to animal models and human in translational research.
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http://dx.doi.org/10.1088/1748-605X/abe6d8DOI Listing
March 2021

Enhancement of mechanical and corrosion resistance properties of electrodeposited Ni-P-TiC composite coatings.

Sci Rep 2021 Mar 5;11(1):5327. Epub 2021 Mar 5.

Department of Mechanical and Mechatronics Engineering, College of Engineering, Dhofar University, Salalah, Oman.

In the present study, the effect of concentration of titanium carbide (TiC) particles on the structural, mechanical, and electrochemical properties of Ni-P composite coatings was investigated. Various amounts of TiC particles (0, 0.5, 1.0, 1.5, and 2.0 g L) were co-electrodeposited in the Ni-P matrix under optimized conditions and then characterized by employing various techniques. The structural analysis of prepared coatings indicates uniform, compact, and nodular structured coatings without any noticeable defects. Vickers microhardness and nanoindentation results demonstrate the increase in the hardness with an increasing amount of TiC particles attaining its terminal value (593HV) at the concentration of 1.5 g L. Further increase in the concentration of TiC particles results in a decrease in hardness, which can be ascribed to their accumulation in the Ni-P matrix. The electrochemical results indicate the improvement in corrosion protection efficiency of coatings with an increasing amount of TiC particles reaching to ~ 92% at 2.0 g L, which can be ascribed to a reduction in the active area of the Ni-P matrix by the presence of inactive ceramic particles. The favorable structural, mechanical, and corrosion protection characteristics of Ni-P-TiC composite coatings suggest their potential applications in many industrial applications.
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http://dx.doi.org/10.1038/s41598-021-84716-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970875PMC
March 2021

Stem cells basedmodels: Trends and prospects in biomaterials cytotoxicity studies.

Biomed Mater 2021 Feb 16. Epub 2021 Feb 16.

Department of Mechanical and Industrial Engineering, Qatar University, Qatar University, Doha, Ad Dawhah, 2713, QATAR.

Advanced biomaterials have produced a significant impact on healthcare by improving the quality of life of people with disabilities. Biomaterials are immensely used in tissue engineering, wound healing applications, and delivery of cancer targeted therapeutics. Biocompatibility and cytotoxicity screening of biomaterials on cell culture systems is the first step before their in vivo testing in animal models and subsequent clinical trials. Direct use of biomaterials on animals may create technical challenges as well as ethical concerns. In order to avoid the ethical concerns of animal use, many non-animal models such as stem cell cultures are being developed and utilized for testing their safety. However, due to several limitations including the inability to recapitulate the complex in vivo microenvironment, the application of stem cell cultures is limited. However, properties of stem cells such as their self-renewal and ability to differentiate into various cell lineages like hepatocytes, cardiomyocytes, and neural cells make them an ideal candidates for in vitro screening studies. Furthermore, the application of stem cells may overcome the challenges associated with the inability to develop a complex heterogeneous tissue using primary cells. Currently, Embryonic Stem Cells (ESCs), Adult Stem Cells (ASCs), and Induced Pluripotent Stem Cells (iPSCs) are being used as in vitro preliminary biomaterials testing models with demonstrated advantages over mature primary cell or cell line based in vitro models. This review discusses the current status and future directions of in vitro stem cell-based cultures and their derivatives such as spheroids and organoids for the screening of their safety before their application to animal models and human in translational research.
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http://dx.doi.org/10.1088/1748-605X/abe6d8DOI Listing
February 2021

3D Bioprinted cancer models: Revolutionizing personalized cancer therapy.

Transl Oncol 2021 Apr 22;14(4):101015. Epub 2021 Jan 22.

Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, 2713 Doha, Qatar; Biomedical Research Center (BRC), Qatar University, PO Box 2713 Doha, Qatar. Electronic address:

After cardiovascular disease, cancer is the leading cause of death worldwide with devastating health and economic consequences, particularly in developing countries. Inter-patient variations in anti-cancer drug responses further limit the success of therapeutic interventions. Therefore, personalized medicines approach is key for this patient group involving molecular and genetic screening and appropriate stratification of patients to treatment regimen that they will respond to. However, the knowledge related to adequate risk stratification methods identifying patients who will respond to specific anti-cancer agents is still lacking in many cancer types. Recent advancements in three-dimensional (3D) bioprinting technology, have been extensively used to generate representative bioengineered tumor in vitro models, which recapitulate the human tumor tissues and microenvironment for high-throughput drug screening. Bioprinting process involves the precise deposition of multiple layers of different cell types in combination with biomaterials capable of generating 3D bioengineered tissues based on a computer-aided design. Bioprinted cancer models containing patient-derived cancer and stromal cells together with genetic material, extracellular matrix proteins and growth factors, represent a promising approach for personalized cancer therapy screening. Both natural and synthetic biopolymers have been utilized to support the proliferation of cells and biological material within the personalized tumor models/implants. These models can provide a physiologically pertinent cell-cell and cell-matrix interactions by mimicking the 3D heterogeneity of real tumors. Here, we reviewed the potential applications of 3D bioprinted tumor constructs as personalized in vitro models in anticancer drug screening and in the establishment of precision treatment regimens.
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http://dx.doi.org/10.1016/j.tranon.2021.101015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823217PMC
April 2021

Cerium Oxide Nanoparticle Incorporated Electrospun Poly(3-hydroxybutyrate--3-hydroxyvalerate) Membranes for Diabetic Wound Healing Applications.

ACS Biomater Sci Eng 2020 01 23;6(1):58-70. Epub 2019 Jul 23.

Biomedical Research Centre, Qatar University, Doha-2713, Qatar.

Insufficient cell proliferation, cell migration, and angiogenesis are among the major causes for nonhealing of chronic diabetic wounds. Incorporation of cerium oxide nanoparticles (nCeO) in wound dressings can be a promising approach to promote angiogenesis and healing of diabetic wounds. In this paper, we report the development of a novel nCeO containing electrospun poly(3-hydroxybutyrate--3-hydroxyvalerate) (PHBV) membrane for diabetic wound healing applications. cell adhesion studies, chicken embryo angiogenesis assay, and diabetic wound healing studies were performed to assess the cell proliferation, angiogenesis, and wound healing potential of the developed membranes. The experimental results showed that nCeO containing PHBV membranes can promote cell proliferation and cell adhesion when used as wound dressings. For less than 1% w/w of nCeO content, human mammary epithelial cells (HMEC) were adhered parallel to the individual fibers of PHBV. For higher than 1% w/w of nCeO content, cells started to flatten and spread over the fibers. angiogenic assay showed the ability of nCeO incorporated PHBV membranes to enhance blood vessel formation. wound healing study in diabetic rats confirmed the wound healing potential of nCeO incorporated PHBV membranes. The study suggests that nCeO incorporated PHBV membranes have strong potential to be used as wound dressings to enhance cell proliferation and vascularization and promote the healing of diabetic wounds.
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http://dx.doi.org/10.1021/acsbiomaterials.8b01352DOI Listing
January 2020

Antimetastatic Activity of Lactoferrin-Coated Mesoporous Maghemite Nanoparticles in Breast Cancer Enabled by Combination Therapy.

ACS Biomater Sci Eng 2020 06 13;6(6):3574-3584. Epub 2020 May 13.

Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran 1234567, Iran.

Despite successes in breast cancer treatment, the incidence of metastasis, drug resistance, and toxicity limit the efficacy of current therapeutic modalities. Herein, by designing lactoferrin-doxorubicin-mesoporous maghemite nanoparticles (Lf-Doxo-MMNPs), we not only provided targeted drug delivery (TDD), but also enabled chemotherapy/magnetic field/photothermal (chemo/MF/PTT) combination therapy to mitigate breast cancer proliferation and metastasis. After synthesizing Lf-Doxo-MMNPs by hydrothermal method and characterizing their features, we examined their effect on the body weight, tumor growth inhibition (TGI), tumor size, Doxo and iron biodistribution, histopathology of metastatic lung tissue, heart tissue, and breast tumor, cell death mechanisms, and metastatic gene expression. The results showed that Lf-Doxo-MMNPs, in addition to enhancing anticancer effects , resulted in a significant increase in body weight, TGI, and targeted drug delivery (TDD). In addition to the significant impacts of Lf-Doxo-MMNPs on the reduction of cancer cell proliferation, their application in chemo/MF/PTT combination therapy has a remarkable effect on the antimetastatic activities against breast tumors. Indeed, chemo/MF/PTT combination therapy exhibited the most reduction in metastatic activity of breast cancer based on controlling C-X-C motif chemokine ligand 12 (CXCL12) and chemokine receptor 7 (CXCR7) mRNA expression. In conclusion, the promising results of Doxo accumulation, reduced cancer cell proliferation, and inhibition of metastatic mRNA expression indicated that MMNPs provide a potential platform for combined therapeutic approaches.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00086DOI Listing
June 2020

Arabinoxylan/graphene-oxide/nHAp-NPs/PVA bionano composite scaffolds for fractured bone healing.

J Tissue Eng Regen Med 2021 04 9;15(4):322-335. Epub 2021 Mar 9.

Sustainable Energy Technologies Center, College of Engineering, King Saud University, Riyadh, Saudi Arabia.

The importance of bone scaffolds has increased many folds in the last few years; however, during bone implantation, bacterial infections compromise the implantation and tissue regeneration. This work is focused on this issue while not compromising on the properties of a scaffold for bone regeneration. Biocomposite scaffolds (BS) were fabricated via the freeze-drying technique. The samples were characterized for structural changes, surface morphology, porosity, and mechanical properties through spectroscopic (Fourier transform-infrared [FT-IR]), microscopic (scanning electron microscope [SEM]), X-ray (powder X-ray diffraction and energy-dispersive X-ray), and other analytical (Brunauer-Emmett-Teller, universal testing machine Instron) techniques. Antibacterial, cellular, and hemocompatibility assays were performed using standard protocols. FT-IR confirmed the interactions of all the components. SEM illustrated porous and interconnected porous morphology. The percentage porosity was in the range of 49.75%-67.28%, and the pore size was 215.65-470.87 µm. The pore size was perfect for cellular penetration. Thus, cells showed significant proliferation onto these scaffolds. X-ray studies confirmed the presence of nanohydroxyapatite and graphene oxide (GO). The cell viability was 85%-98% (BS1-BS3), which shows no significant toxicity of the biocomposite. Furthermore, the biocomposites exhibited better antibacterial activity, no effect on the blood clotting (normal in vitro blood clotting), and less than 5% hemolysis. The ultimate compression strength for the biocomposites increased from 4.05 to 7.94 with an increase in the GO content. These exciting results revealed that this material has the potential for possible application in bone tissue engineering.
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http://dx.doi.org/10.1002/term.3168DOI Listing
April 2021

Gelatin-methacryloyl hydrogel based blood-brain barrier model for studying breast cancer-associated brain metastasis.

Pharm Dev Technol 2021 Apr 15;26(4):490-500. Epub 2021 Feb 15.

Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha, Qatar.

Breast cancer is one of the leading causes of brain metastasis. Metastasis to the brain occurs if cancer cells manage to traverse the 'blood-brain barrier' (BBB), which is a barrier with a very tight junction (TJ) of endothelial cells between blood circulation and brain tissue. It is highly important to develop novel BBB models to investigate breast cancer metastasis to the brain to facilitate the screening of chemotherapeutic agents against it. We herein report the development of gelatin methacryloyl (GelMA) modified transwell insert based BBB model composed of endothelial and astrocyte cell layers for testing the efficacy of anti-metastatic agents against breast cancer metastasis to the brain. We characterized the developed model for the morphology and in vitro breast cancer cell migration. Furthermore, we investigated the effect of cisplatin, a widely used chemotherapeutic agent, on the migration of metastatic breast cancer cells using the model. Our results showed that breast cancer cells migrate across the developed BBB model. Cisplatin treatment inhibited the migration of cancer cells across the model. Findings of this study suggest that our BBB model can be used as a suitable tool to investigate breast cancer-associated brain metastasis and to identify suitable therapeutic agents against this.
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http://dx.doi.org/10.1080/10837450.2021.1872624DOI Listing
April 2021

Hydrothermal method-based synthesized tin oxide nanoparticles: Albumin binding and antiproliferative activity against K562 cells.

Mater Sci Eng C Mater Biol Appl 2021 Feb 17;119:111649. Epub 2020 Oct 17.

College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China; Cancer Institute of Jinan University, Guangzhou, Guangdong 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), School of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China. Electronic address:

The interaction of nanoparticles with protein and cells may provide important information regarding their biomedical implementations. Herein, after synthesis of tin oxide (SnO) nanoparticles by hydrothermal method, their interaction with human serum albumin (HSA) was evaluated by multispectroscopic and molecular docking (MD) approaches. Furthermore, the selective antiproliferative impact of SnO nanoparticles against leukemia K562 cells was assessed by different cellular assays, whereas lymphocytes were used as control cells. TEM, DLS, zeta potential and XRD techniques showed that crystalline SnO nanoparticles have a size of less than 50 nm with a good colloidal stability. Fluorescence and CD spectroscopy analysis indicated that the HSA undergoes some slight conformational changes after interaction with SnO nanoparticles, whereas the secondary structure of HSA remains intact. Moreover, MD outcomes revealed that the charged residues of HSA preferentially bind to SnO nanoclusters in the binding pocket. Antiproliferative examinations displayed that SnO nanoparticles can selectively cause the mortality of K562 cells through induction of cell membrane leakage, activation of caspase-9, -8, -3, down regulation of Bcl-2 mRNA, the elevation of ROS level, S phase arrest, and apoptosis. In conclusion, this data may indicate that SnO nanoparticles can be used as promising particles to be integrated into therapeutic platforms.
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http://dx.doi.org/10.1016/j.msec.2020.111649DOI Listing
February 2021

Gold Nanoparticle-Based Platforms for Diagnosis and Treatment of Myocardial Infarction.

ACS Biomater Sci Eng 2020 12 17;6(12):6460-6477. Epub 2020 Nov 17.

Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

In recent years, an increasing rate of mortality due to myocardial infarction (MI) has led to the development of nanobased platforms, especially gold nanoparticles (AuNPs), as promising nanomaterials for diagnosis and treatment of MI. These promising NPs have been used to develop different nanobiosensors, mainly optical sensors for early detection of biomarkers as well as biomimetic/bioinspired platforms for cardiac tissue engineering (CTE). Therefore, in this Review, we presented an overview on the potential application of AuNPs as optical (surface plasmon resonance, colorimetric, fluorescence, and chemiluminescence) nanobiosensors for early diagnosis and prognosis of MI. On the other hand, we discussed the potential application of AuNPs either alone or with other NPs/polymers as promising three-dimensional (3D) scaffolds to regulate the microenvironment and mimic the morphological and electrical features of cardiac cells for potential application in CTE. Furthermore, we presented the challenges and ongoing efforts associated with the application of AuNPs in the diagnosis and treatment of MI. In conclusion, this Review may provide outstanding information regarding the development of AuNP-based technology as a promising platform for current MI treatment approaches.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00955DOI Listing
December 2020

Cerium Oxide Nanoparticle-Loaded Gelatin Methacryloyl Hydrogel Wound-Healing Patch with Free Radical Scavenging Activity.

ACS Biomater Sci Eng 2021 01 14;7(1):279-290. Epub 2020 Dec 14.

Pushpagiri Research Centre, Pushpagiri Institute of Medical Science & Research, Tiruvalla 689101, Kerala, India.

Nonhealing wounds in diabetic patients are a critical challenge, which often cause amputation and mortality. High levels of oxidative stress and aberrations in antioxidant defense mechanisms increase the adverse manifestations of diabetes mellitus. In this study, we developed a biodegradable gelatin methacryloyl (GelMA) hydrogel patch incorporated with cerium oxide nanoparticles (CONPs) for promoting diabetic wound healing. The patches were thoroughly characterized for the morphology, physicomechanical properties, free radical scavenging activity, cell proliferation, and diabetic wound healing activity. Highly porous and biodegradable patches showed excellent exudate uptake capacity as evident from the many-fold weight gain (400-700 times) when placed in aqueous medium. Results of free radical scavenging assays clearly indicated that the patches loaded with 1-4% w/w CONPs could effectively inactivate experimentally generated free radicals. Obtained results of cell culture studies clearly indicated that CONP-incorporated patches could favor the proliferation of skin-associated cells such as keratinocytes and fibroblasts. Results of the wound healing study showed that 1% w/w CONP-loaded patches could effectively improve the healing of wounds in diabetic rats. Overall results indicate that CONP-loaded GelMA hydrogels are highly promising materials for developing clinically relevant patches for treating diabetic wounds.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01138DOI Listing
January 2021

Ferritin Nanocage Conjugated Hybrid Hydrogel for Tissue Engineering and Drug Delivery Applications.

ACS Biomater Sci Eng 2020 01 5;6(1):277-287. Epub 2019 Nov 5.

Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, United States.

Hydrogels have recently been attractive in various drug delivery and tissue engineering applications because of their structural similarities to the natural extracellular matrix. Despite enormous advances in the application of hydrogels, poor mechanical properties and lack of control for the release of drugs and biomolecules act as major barriers for widespread clinical applications. To overcome these challenges, we developed both physically and covalently conjugated nanocage-laden hydrogels between the surface of the nanocage and a gelatin methacryloyl (GelMA) hydrogel matrix. Ferritin and its empty-core equivalent apoferritin were used as nanocages that could be easily incorporated into a GelMA hydrogel via physical bonding. To fabricate covalently conjugated nanocage-laden GelMA hydrogels, ferritin and apoferritin were chemically modified to present the methacryloyl groups, ferritin methacryloyl (FerMA) and apoferritin methacryloyl (ApoMA), respectively. The covalently conjugated FerMA- and ApoMA-GelMA hydrogels offered a better ability to tune mechanical properties compared with those prepared by direct dispersion of ferritin and apoferritin into GelMA hydrogels with physical bonding, without affecting their porosity or cell growth. Furthermore, the ability of the nanocage to release small chemical compounds was confirmed by performing a cumulative release test on fluorescein isothiocyanate (FITC) encapsulated apoferritin and ApoMA incorporated GelMA hydrogels by pH stimulus. Thus, the nanocage incorporated hydrogels have emerged as excellent materials for drug delivery and tissue engineering applications.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725239PMC
January 2020

Rapid diagnostics of coronavirus disease 2019 in early stages using nanobiosensors: Challenges and opportunities.

Talanta 2021 Feb 28;223(Pt 1):121704. Epub 2020 Sep 28.

Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Electronic address:

The rapid outbreak of coronavirus disease 2019 (COVID-19) around the world is a tragic and shocking event that demonstrates the unpreparedness of humans to develop quick diagnostic platforms for novel infectious diseases. In fact, statistical reports of diagnostic tools show that their accuracy, specificity and sensitivity in the detection of COVID hampered by some challenges that can be eliminated by using nanoparticles (NPs). In this study, we aimed to present an overview on the most important ways to diagnose different kinds of viruses followed by the introduction of nanobiosensors. Afterward, some methods of COVID-19 detection such as imaging, laboratory and kit-based diagnostic tests are surveyed. Furthermore, nucleic acids/protein- and immunoglobulin (Ig)-based nanobiosensors for the COVID-19 detection infection are reviewed. Finally, current challenges and future perspective for the development of diagnostic or monitoring technologies in the control of COVID-19 are discussed to persuade the scientists in advancing their technologies beyond imagination. In conclusion, it can be deduced that as rapid COVID-19 detection infection can play a vital role in disease control and treatment, this review may be of great help for controlling the COVID-19 outbreak by providing some necessary information for the development of portable, accurate, selectable and simple nanobiosensors.
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http://dx.doi.org/10.1016/j.talanta.2020.121704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521920PMC
February 2021

Growth factor loaded in situ photocrosslinkable poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/gelatin methacryloyl hybrid patch for diabetic wound healing.

Mater Sci Eng C Mater Biol Appl 2021 Jan 18;118:111519. Epub 2020 Sep 18.

Biomedical Research Center, Qatar University, Doha 2713, Qatar; College of Medicine, QU Health, Qatar University, Doha 2713, Qatar.

Management of chronic diabetic ulcers remains as a major challenge in healthcare which requires extensive multidisciplinary approaches to ensure wound protection, management of excess wound exudates and promoting healing. Developing wound healing patches that can act as a protective barrier and support healing is highly needed to manage chronic diabetic ulcers. In order to boost the wound healing potential of patch material, bioactive agents such as growth factors can be used. Porous membranes made of nanofibers generated using electrospinning have potential for application as wound coverage matrices. However, electrospun membranes produced from several biodegradable polymers are hydrophobic and cannot manage the excess exudates produced by chronic wounds. Gelatin-methacryloyl (GelMA) hydrogels absorb excess exudates and provide an optimal biological environment for the healing wound. Epidermal growth factor (EGF) promotes cell migration, angiogenesis and overall wound healing. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) membranes provide microbial, thermal and mechanical barrier properties to the wound healing patch. Herein, we developed a biodegradable polymeric patch based on the combination of mechanically stable electrospun PHBV, GelMA hydrogel and EGF for promoting diabetic wound healing. In vitro and in vivo studies were carried out to evaluate the effect of developed patches on cell proliferation, cell migration, angiogenesis and wound healing. Our results showed that EGF loaded patches can promote the migration and proliferation of multiple types of cells (keratinocytes, fibroblasts and endothelial cells) and enhance angiogenesis. In situ development of the patch and subsequent in vivo wound healing study in diabetic rats showed that EGF loaded patches provide rapid healing compared to control wounds. Interestingly, 100 ng EGF per cm of the patches was enough to provide favourable cellular response, angiogenesis and rapid diabetic wound healing. Overall results indicate that EGF loaded PHBV-GelMA hybrid patch could be a promising approach to promote diabetic wound healing.
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http://dx.doi.org/10.1016/j.msec.2020.111519DOI Listing
January 2021

Recent advances in 3D bioprinting of musculoskeletal tissues.

Biofabrication 2020 Nov 9. Epub 2020 Nov 9.

University of California Los Angeles, Los Angeles, California, UNITED STATES.

The musculoskeletal system is essential for maintaining posture, protecting organs, facilitating locomotion, and regulating various cellular and metabolic functions. Injury to this system due to trauma or wear is common, and severe damage may require surgery to restore function and prevent further harm. Autografts are the current gold standard for the replacement of lost or damaged tissues. However, these grafts are constrained by limited supply and donor site morbidity. Allografts, xenografts, and alloplastic materials represent viable alternatives, but each of these methods also has its own problems and limitations. Technological advances in three-dimensional (3D) printing and its biomedical adaptation, 3D bioprinting, have the potential to provide viable, autologous tissue-like constructs that can be used to repair musculoskeletal defects. Though bioprinting is currently unable to develop mature, implantable tissues, it can pattern cells in 3D constructs with features facilitating maturation and vascularization. Further advances in the field may enable the manufacture of constructs that can mimic native tissues in complexity, spatial heterogeneity, and ultimately, clinical utility. This review studies the use of 3D bioprinting for engineering bone, cartilage, muscle, tendon, ligament, and their interface tissues. Additionally, the current limitations and challenges in the field are discussed and the prospects for future progress are highlighted.
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http://dx.doi.org/10.1088/1758-5090/abc8deDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312688PMC
November 2020

Polymeric-based microneedle arrays as potential platforms in the development of drugs delivery systems.

J Adv Res 2020 Nov 1;26:137-147. Epub 2020 Aug 1.

College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China.

Background: Microscopic patches as quite promising platforms in transdermal drug delivery suffer from conventional injections. In other hand, a wide range of pharmacokinetics, ranging from fast oral administration to sustained drug delivery, can be implemented with the help of microneedle arrays (MNAs).

Aim Of Review: Hence, in this paper, we overviewed different kinds of MNAs such as solid/coated, hollow, porous, hydrogel/swellable, and merged-tip geometry followed by introducing different types of material (silicon, glass, ceramics, dissolving and biodegradable polymers, and hydrogel) used for fabrication of MNAs. Afterwards, some conventional and brand-new simple and customizable MN mold fabrication techniques were surveyed. Polymeric MNAs have received a great deal of attention due to their potential biocompatibility and biodegradability in comparison to other materials. Therefore, we also covered different kinds of polymers such as hydrogel/swellable, dissolving and biodegradable analogues used for the development of MNAs as potential candidates in drug delivery systems (DDSs). Finally, we discussed different challenges and future perspectives in the aspect of MNAs-based drug delivery platforms.

Key Scientific Concepts Of Review: This review may provide guidelines for the rational design of polymeric MNAs-based DDSs for promising programmable drug release and enhanced therapeutic effect.
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http://dx.doi.org/10.1016/j.jare.2020.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584683PMC
November 2020

Rapid Antibody-Based COVID-19 Mass Surveillance: Relevance, Challenges, and Prospects in a Pandemic and Post-Pandemic World.

J Clin Med 2020 Oct 21;9(10). Epub 2020 Oct 21.

Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304, USA.

The aggressive outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as COVID-19 (coronavirus disease-2019) pandemic demands rapid and simplified testing tools for its effective management. Increased mass testing and surveillance are crucial for controlling the disease spread, obtaining better pandemic statistics, and developing realistic epidemiological models. Despite the advantages of nucleic acid- and antigen-based tests such as accuracy, specificity, and non-invasive approaches of sample collection, they can only detect active infections. Antibodies (immunoglobulins) are produced by the host immune system within a few days after infection and persist in the blood for at least several weeks after infection resolution. Antibody-based tests have provided a substitute and effective method of ultra-rapid detection for multiple contagious disease outbreaks in the past, including viral diseases such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Thus, although not highly suitable for early diagnosis, antibody-based methods can be utilized to detect past infections hidden in the population, including asymptomatic ones. In an active community spread scenario of a disease that can provide a bigger window for mass detections and a practical approach for continuous surveillance. These factors encouraged researchers to investigate means of improving antibody-based rapid tests and employ them as reliable, reproducible, sensitive, specific, and economic tools for COVID-19 mass testing and surveillance. The development and integration of such immunoglobulin-based tests can transform the pandemic diagnosis by moving the same out of the clinics and laboratories into community testing sites and homes. This review discusses the principle, technology, and strategies being used in antibody-based testing at present. It also underlines the immense prospect of immunoglobulin-based testing and the efficacy of repeated planned deployment in pandemic management and post-pandemic sustainable screenings globally.
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http://dx.doi.org/10.3390/jcm9103372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589650PMC
October 2020

Bone marrow mesenchymal stem cells preconditioned with nitric-oxide-releasing chitosan/PVA hydrogel accelerate diabetic wound healing in rabbits.

Biomed Mater 2021 03 1;16(3). Epub 2021 Mar 1.

Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar.

Impaired diabetic wounds are one of the major pathophysiological complications caused by persistent microbial infections, prolonged inflammation, and insufficient angiogenic responses. Here, we report the development of nitric-oxide (NO) -releasing S-nitroso-N-acetyl-penicillamine (SNAP) -loaded chitosan/polyvinyl-alcohol hydrogel and its efficacy in enhancing the wound-healing potential of bone marrow mesenchymal stem cells in diabetic wounds. NO-releasing hydrogels significantly increased the cell viability and cell proliferation of hydrogen-peroxide (HO) -pretreated bone marrow stem cells (BMSCs), demonstrating their cytoprotective activity, which was further confirmed by gene expression of many times as much B-cell lymphoma 2 (Bcl-2), stromal cell-derived factor-1alpha (SDF-1α), proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF). Furthermore, the SNAP-loaded hydrogel showed continuous cell-proliferating activity for six days, due to the slow release of NO from the hydrogel. Wound-healing studies of rabbits with induced diabetes showed that the application of SNAP-preconditioned BMSCs and NO-releasing hydrogels significantly sped up the healing process, compared to the control group. The wound-healing potential of BMSCs plus NO-releasing hydrogel was further validated by improved collagen deposition and epithelial layer formation, as confirmed by histopathological examination, as well as upregulation of VEGF and SDF-1α biomarkers, as evidenced by gene-expression analysis. These results demonstrated that the application of BMSCs with NO-releasing hydrogel can promote faster regeneration of damaged tissues. Therefore, BMSCs plus NO-releasing hydrogels can be very useful for the treatment of diabetic wounds.
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http://dx.doi.org/10.1088/1748-605X/abc28bDOI Listing
March 2021

Advances of exosome isolation techniques in lung cancer.

Mol Biol Rep 2020 Sep 12;47(9):7229-7251. Epub 2020 Aug 12.

Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box: 14115-154, Tehran, Iran.

Lung cancer (LC) is among the leading causes of death all over the world and it is often diagnosed at advanced or metastatic stages. Exosomes, derived from circulating vesicles that are released from the multivesicular body, can be utilized for diagnosis and also the prognosis of LC at early stages. Exosomal proteins, RNAs, and DNAs can help to better discern the prognostic and diagnostic features of LC. To our knowledge, there are various reviews on LC and the contribution of exosomes, but none of them are about the exome techniques and also their efficiency in LC. To fill this gap, in this review, we summarize the recent investigations regarding isolation and also the characterization of exosomes of LC cells. Furthermore, we discuss the noncoding RNAs as biomarkers and their applications in the diagnosis and prognosis of LC. Finally, we compare the efficacy of exosome isolation methods to better fi + 6 + guring out feasible techniques.
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http://dx.doi.org/10.1007/s11033-020-05715-wDOI Listing
September 2020
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