Soluble chitosan derivative treats wound infections and promotes wound healing in a novel MRSA-infected porcine partial-thickness burn wound model
Burns are physically debilitating and potentially fatal injuries. The most common etiology of burn wound infections in the US is methicillin-resistant Staphylococcus aureus (MRSA), which is particularly recalcitrant when biofilms form. The current standard of care, silver sulfadiazine (SSD) is effec...
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creator | Egro, Francesco Repko, Alex Narayanaswamy, Vidya Ejaz, Asim Kim, Deokyeol Schusterman, M. Asher Loughran, Allister Ayyash, Ali Towsend, Stacy M Baker, Shenda Ziembicki, Jenny Marra, Kacey Rubin, Peter |
description | Burns are physically debilitating and potentially fatal injuries. The most common etiology of burn wound infections in the US is methicillin-resistant Staphylococcus aureus (MRSA), which is particularly recalcitrant when biofilms form. The current standard of care, silver sulfadiazine (SSD) is effective in reducing bacterial load, but less effective in improving burn wound healing. New treatments that can manage infection while simultaneously improving healing would provide a benefit in the treatment of burns. Porcine models are frequently used as a model for human wound healing but can be expensive due to the need to separate wounds to avoid cross contamination. The porcine model developed in this study offers the capability to study multiple partial thickness burn wound (PTBW) sites on a single animal with minimal crosstalk to study wound healing, infection, and inflammation. The current study evaluates a wound rinse and a wound gel formulated with a non-toxic, polycationic chitosan derivative that is hypothesized to manage infection while also promoting healing, providing a potential alternate to SSD. Studies in vitro and in this PTBW porcine model compare treatment with the chitosan derivative formulations to SSD. The wound rinse and wound gel are observed to disrupt mature MRSA biofilms in vitro and reduce the MRSA load in vivo when compared to that of the standard of care. In vivo data further show increased re-epithelialization and faster healing in burns treated with wound rinse/gel as compared to SSD. Taken together, the data demonstrate the potential of the wound rinse/gel to significantly enhance healing, promote re-epithelialization, and reduce bacterial burden in infected PTBW using an economical porcine model. |
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Asher ; Loughran, Allister ; Ayyash, Ali ; Towsend, Stacy M ; Baker, Shenda ; Ziembicki, Jenny ; Marra, Kacey ; Rubin, Peter</creator><creatorcontrib>Egro, Francesco ; Repko, Alex ; Narayanaswamy, Vidya ; Ejaz, Asim ; Kim, Deokyeol ; Schusterman, M. Asher ; Loughran, Allister ; Ayyash, Ali ; Towsend, Stacy M ; Baker, Shenda ; Ziembicki, Jenny ; Marra, Kacey ; Rubin, Peter</creatorcontrib><description>Burns are physically debilitating and potentially fatal injuries. The most common etiology of burn wound infections in the US is methicillin-resistant Staphylococcus aureus (MRSA), which is particularly recalcitrant when biofilms form. The current standard of care, silver sulfadiazine (SSD) is effective in reducing bacterial load, but less effective in improving burn wound healing. New treatments that can manage infection while simultaneously improving healing would provide a benefit in the treatment of burns. Porcine models are frequently used as a model for human wound healing but can be expensive due to the need to separate wounds to avoid cross contamination. The porcine model developed in this study offers the capability to study multiple partial thickness burn wound (PTBW) sites on a single animal with minimal crosstalk to study wound healing, infection, and inflammation. The current study evaluates a wound rinse and a wound gel formulated with a non-toxic, polycationic chitosan derivative that is hypothesized to manage infection while also promoting healing, providing a potential alternate to SSD. Studies in vitro and in this PTBW porcine model compare treatment with the chitosan derivative formulations to SSD. The wound rinse and wound gel are observed to disrupt mature MRSA biofilms in vitro and reduce the MRSA load in vivo when compared to that of the standard of care. In vivo data further show increased re-epithelialization and faster healing in burns treated with wound rinse/gel as compared to SSD. Taken together, the data demonstrate the potential of the wound rinse/gel to significantly enhance healing, promote re-epithelialization, and reduce bacterial burden in infected PTBW using an economical porcine model.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0274455</identifier><identifier>PMID: 36240206</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Animal models ; Antibiotics ; Bacteria ; Bacterial infections ; Biocompatibility ; Biofilms ; Biology and Life Sciences ; Burns ; Burns and scalds ; Care and treatment ; Chitin ; Chitosan ; Contamination ; Debridement ; Drug resistance ; Economic models ; Etiology ; Evaluation ; Experiments ; Gene expression ; Gram-positive bacteria ; Health aspects ; Hydrogels ; Infection control ; Infections ; Inflammation ; Laboratory animals ; Medical technology ; Medicine and health sciences ; Methicillin ; Methods ; Modelling ; Patient outcomes ; Physical Sciences ; Research and Analysis Methods ; Staphylococcus aureus ; Staphylococcus infections ; Sulfadiazine ; Thickness ; Wound healing ; Wounds and injuries</subject><ispartof>PloS one, 2022-10, Vol.17 (10), p.e0274455-e0274455</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Egro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Egro et al 2022 Egro et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c669t-e8bd734a47893277b0b0df60d854f7ed08bc9071eccdf7ce277cc947eb490c1d3</citedby><cites>FETCH-LOGICAL-c669t-e8bd734a47893277b0b0df60d854f7ed08bc9071eccdf7ce277cc947eb490c1d3</cites><orcidid>0000-0003-1148-6205 ; 0000-0002-8194-3371</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9565743/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9565743/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids></links><search><creatorcontrib>Egro, Francesco</creatorcontrib><creatorcontrib>Repko, Alex</creatorcontrib><creatorcontrib>Narayanaswamy, Vidya</creatorcontrib><creatorcontrib>Ejaz, Asim</creatorcontrib><creatorcontrib>Kim, Deokyeol</creatorcontrib><creatorcontrib>Schusterman, M. Asher</creatorcontrib><creatorcontrib>Loughran, Allister</creatorcontrib><creatorcontrib>Ayyash, Ali</creatorcontrib><creatorcontrib>Towsend, Stacy M</creatorcontrib><creatorcontrib>Baker, Shenda</creatorcontrib><creatorcontrib>Ziembicki, Jenny</creatorcontrib><creatorcontrib>Marra, Kacey</creatorcontrib><creatorcontrib>Rubin, Peter</creatorcontrib><title>Soluble chitosan derivative treats wound infections and promotes wound healing in a novel MRSA-infected porcine partial-thickness burn wound model</title><title>PloS one</title><description>Burns are physically debilitating and potentially fatal injuries. The most common etiology of burn wound infections in the US is methicillin-resistant Staphylococcus aureus (MRSA), which is particularly recalcitrant when biofilms form. The current standard of care, silver sulfadiazine (SSD) is effective in reducing bacterial load, but less effective in improving burn wound healing. New treatments that can manage infection while simultaneously improving healing would provide a benefit in the treatment of burns. Porcine models are frequently used as a model for human wound healing but can be expensive due to the need to separate wounds to avoid cross contamination. The porcine model developed in this study offers the capability to study multiple partial thickness burn wound (PTBW) sites on a single animal with minimal crosstalk to study wound healing, infection, and inflammation. The current study evaluates a wound rinse and a wound gel formulated with a non-toxic, polycationic chitosan derivative that is hypothesized to manage infection while also promoting healing, providing a potential alternate to SSD. Studies in vitro and in this PTBW porcine model compare treatment with the chitosan derivative formulations to SSD. The wound rinse and wound gel are observed to disrupt mature MRSA biofilms in vitro and reduce the MRSA load in vivo when compared to that of the standard of care. In vivo data further show increased re-epithelialization and faster healing in burns treated with wound rinse/gel as compared to SSD. Taken together, the data demonstrate the potential of the wound rinse/gel to significantly enhance healing, promote re-epithelialization, and reduce bacterial burden in infected PTBW using an economical porcine model.</description><subject>Animal models</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Bacterial infections</subject><subject>Biocompatibility</subject><subject>Biofilms</subject><subject>Biology and Life Sciences</subject><subject>Burns</subject><subject>Burns and scalds</subject><subject>Care and treatment</subject><subject>Chitin</subject><subject>Chitosan</subject><subject>Contamination</subject><subject>Debridement</subject><subject>Drug resistance</subject><subject>Economic models</subject><subject>Etiology</subject><subject>Evaluation</subject><subject>Experiments</subject><subject>Gene expression</subject><subject>Gram-positive bacteria</subject><subject>Health aspects</subject><subject>Hydrogels</subject><subject>Infection control</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Laboratory animals</subject><subject>Medical technology</subject><subject>Medicine and health sciences</subject><subject>Methicillin</subject><subject>Methods</subject><subject>Modelling</subject><subject>Patient outcomes</subject><subject>Physical Sciences</subject><subject>Research and Analysis Methods</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus infections</subject><subject>Sulfadiazine</subject><subject>Thickness</subject><subject>Wound healing</subject><subject>Wounds and injuries</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk8-O0zAQxiMEYpfCGyARCQnBIcVJ7Di5IFUr_lRatNIWuFqOPWldXLtrOwVegyfGabNog_aAfIhj_-azZ_xNkjzP0Twvaf52a3tnuJ7vrYE5KijGhDxIzvOmLLKqQOXDO_Oz5In3W4RIWVfV4-SsrAqMClSdJ79XVvethlRsVLCem1SCUwce1AHS4IAHn_6wvZGpMh2IoKzxKY-_e2d3NsDt7ga4VmYdqZSnxh5Ap5-vV4vsFAWRt04oA-meu6C4zsJGie8GvE_bmMeosrMS9NPkUce1h2fjd5Z8_fD-y8Wn7PLq4_JicZmJqmpCBnUraYk5pnVMk9IWtUh2FZI1wR0FiepWNIjmIITsqICICNFgCi1ukMhlOUtenHT32no2ltOzgha4rhocizdLlidCWr5le6d23P1ilit2XLBuzYZshAaWI0q7okVFWZVY1g2XkmCCCKG8wC0uo9a78bS-3YEUYILjeiI63TFqw9b2wBpSEXoUeD0KOHvTgw9sp7wArbkB2x_vTYr4qGS498t_0PuzG6k1jwnEh7LxXDGIsgUtokHqBuFIze-h4pCwUyJ6r1NxfRLwZhIQmQA_w5r33rPl6vr_2atvU_bVHXbwW9j4aN6jJacgPoHCWe8ddH-LnCM2tM5tNdjQOmxsnfIPdMEMVw</recordid><startdate>20221014</startdate><enddate>20221014</enddate><creator>Egro, Francesco</creator><creator>Repko, Alex</creator><creator>Narayanaswamy, Vidya</creator><creator>Ejaz, Asim</creator><creator>Kim, Deokyeol</creator><creator>Schusterman, M. 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The current standard of care, silver sulfadiazine (SSD) is effective in reducing bacterial load, but less effective in improving burn wound healing. New treatments that can manage infection while simultaneously improving healing would provide a benefit in the treatment of burns. Porcine models are frequently used as a model for human wound healing but can be expensive due to the need to separate wounds to avoid cross contamination. The porcine model developed in this study offers the capability to study multiple partial thickness burn wound (PTBW) sites on a single animal with minimal crosstalk to study wound healing, infection, and inflammation. The current study evaluates a wound rinse and a wound gel formulated with a non-toxic, polycationic chitosan derivative that is hypothesized to manage infection while also promoting healing, providing a potential alternate to SSD. Studies in vitro and in this PTBW porcine model compare treatment with the chitosan derivative formulations to SSD. The wound rinse and wound gel are observed to disrupt mature MRSA biofilms in vitro and reduce the MRSA load in vivo when compared to that of the standard of care. In vivo data further show increased re-epithelialization and faster healing in burns treated with wound rinse/gel as compared to SSD. Taken together, the data demonstrate the potential of the wound rinse/gel to significantly enhance healing, promote re-epithelialization, and reduce bacterial burden in infected PTBW using an economical porcine model.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>36240206</pmid><doi>10.1371/journal.pone.0274455</doi><tpages>e0274455</tpages><orcidid>https://orcid.org/0000-0003-1148-6205</orcidid><orcidid>https://orcid.org/0000-0002-8194-3371</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animal models Antibiotics Bacteria Bacterial infections Biocompatibility Biofilms Biology and Life Sciences Burns Burns and scalds Care and treatment Chitin Chitosan Contamination Debridement Drug resistance Economic models Etiology Evaluation Experiments Gene expression Gram-positive bacteria Health aspects Hydrogels Infection control Infections Inflammation Laboratory animals Medical technology Medicine and health sciences Methicillin Methods Modelling Patient outcomes Physical Sciences Research and Analysis Methods Staphylococcus aureus Staphylococcus infections Sulfadiazine Thickness Wound healing Wounds and injuries |
title | Soluble chitosan derivative treats wound infections and promotes wound healing in a novel MRSA-infected porcine partial-thickness burn wound model |
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