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      Nanomedicine and advanced technologies for burns: Preventing infection and facilitating wound healing

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          Abstract

          According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally employed to inhibit burn infections followed by a burn wound therapy, because systemic antibiotics have problems in reaching the infected site, coupled with increasing microbial drug resistance. Nanotechnology has provided a range of molecular designed nanostructures (NS) that can be used in both therapeutic and diagnostic applications in burns. These NSs can be divided into organic and non-organic (such as polymeric nanoparticles (NPs) and silver NPs, respectively), and many have been designed to display multifunctional activity. The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing. These include biological based approaches (e.g. immune-based antimicrobial molecules, therapeutic microorganisms, antimicrobial agents, etc.), antimicrobial photo- and ultrasound-therapy, as well as nanotechnology-based wound healing approaches as a revolutionizing area. Thus, we focus on organic and non-organic NSs designed to deliver growth factors to burned skin, and scaffolds, dressings, etc. for exogenous stem cells to aid skin regeneration. Eventually, recent breakthroughs and technologies with substantial potentials in tissue regeneration and skin wound therapy (that are as the basis of burn wound therapies) are briefly taken into consideration including 3D-printing, cell-imprinted substrates, nano-architectured surfaces, and novel gene-editing tools such as CRISPR-Cas.

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          Antimicrobial Peptides

          The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs), a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes) and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics).
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            Skin immune sentinels in health and disease.

            Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.
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              Pathophysiology of acute wound healing.

              Wound healing is a complex process that can be divided into at least 3 continuous and overlapping processes: an inflammatory reaction, a proliferative process leading to tissue restoration, and, eventually, tissue remodeling. Wound healing processes are strictly regulated by multiple growth factors and cytokines released at the wound site. Although the desirable final result of coordinated healing would be the formation of tissue with a similar structure and comparable functions as with intact skin, regeneration is uncommon (with notable exceptions such as early fetal healing); healing however results in a structurally and functionally satisfactory but not identical outcome. Alterations that disrupt controlled healing processes would extend tissue damage and repair. The pathobiologic states may lead to chronic or nonhealing wounds or excessive fibrosis.
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                Author and article information

                Journal
                8710523
                21484
                Adv Drug Deliv Rev
                Adv. Drug Deliv. Rev.
                Advanced drug delivery reviews
                0169-409X
                1872-8294
                3 November 2017
                04 August 2017
                01 January 2018
                01 January 2019
                : 123
                : 33-64
                Affiliations
                [a ]Department of Advanced Medical Sciences & Technologies, School of Medicine, Jahrom University of Medical Sciences (JUMS), Jahrom, Iran
                [b ]Research Center for Noncommunicable Diseases, School of Medicine, Jahrom University of Medical Sciences (JUMS), Jahrom, Iran
                [c ]Research Center for Pharmaceutical Nanotechnology (RCPN), Tabriz University of Medical Science (TUOMS), Tabriz, Iran
                [d ]Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
                [e ]Bio-Nano-Interfaces: Convergence of Sciences (BNICS), Universal Scientific Education and Research Network (USERN), Tehran, Iran
                [f ]Bioenvironmental Research Center, Sharif University of Technology, Tehran, Iran
                [g ]Civil & Environmental Engineering Department, Shahid Beheshti University, Tehran, Iran
                [h ]Department of Polymer Engineering, Sahand University of Technology, PO Box 51335-1996, Tabriz, Iran
                [i ]Nanomedicine Research Association (NRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
                [j ]Department of Biology, Science and Research Branch, Islamic Azad university, Tehran, Iran
                [k ]Department of Medical Oncology, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215
                [l ]Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
                [m ]Research Center for Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran
                [n ]Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA
                [o ]Department of Dermatology, Harvard Medical School, Boston, USA
                [p ]Harvard-MIT Division of Health Sciences and Technology, Cambridge, USA
                Author notes
                [¶]

                These two authors contributed equally to this work

                Article
                NIHMS898183
                10.1016/j.addr.2017.08.001
                5742034
                28782570
                17a5c8b2-0fa8-404f-ac81-d04615c60902

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

                History
                Categories
                Article

                burn wound infection,wound healing,topical treatment,nanomedicine,nanoparticles,stem cells,stimulus-responsive drug delivery,growth factors,gene therapy,crispr,3d printing,cell-imprinting

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