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810 Synthetic Platelet-Mimetics with Gentamicin: Outcomes in Deep Partial-Thickness Burns

INTRODUCTION: Infection and prolonged inflammation in deep partial-thickness burns can lead to inadequate healing. In addition to their role in hemostasis, activated platelets also contain granules with anti-inflammatory properties which may impact wound healing. However, portability and storage of...

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Autores principales: Valdera, Franklin, Nuutila, Kristo, Cooper, Laura E, Varon, David E, Cooley, Jennifer, Chapa, Javier, Chan, Rodney K, Carlsson, Anders H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946203/
http://dx.doi.org/10.1093/jbcr/irac012.358
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author Valdera, Franklin
Nuutila, Kristo
Cooper, Laura E
Varon, David E
Cooley, Jennifer
Chapa, Javier
Chan, Rodney K
Carlsson, Anders H
author_facet Valdera, Franklin
Nuutila, Kristo
Cooper, Laura E
Varon, David E
Cooley, Jennifer
Chapa, Javier
Chan, Rodney K
Carlsson, Anders H
author_sort Valdera, Franklin
collection PubMed
description INTRODUCTION: Infection and prolonged inflammation in deep partial-thickness burns can lead to inadequate healing. In addition to their role in hemostasis, activated platelets also contain granules with anti-inflammatory properties which may impact wound healing. However, portability and storage of platelets remain a challenge. Synthetic platelet-mimetics (SPM) avoid these difficulties, but like natural platelets, SPM have vesicles that can transport bioactive agents, such as antibiotics. We sought to evaluate wound healing outcomes in deep partial-thickness burns treated topically with SPM. METHODS: A total of 30 circular, deep partial-thickness burns were created on the dorsum of 2 porcine models. Each wound measured 5cm in diameter and was standardized using a thermocoupled burn device. Sets of six wounds were randomized into five groups: SPM, gentamicin alone, SPM with gentamicin, a vehicle control (saline), or dry gauze (the standard of care, SOC). Additionally, two separate 5cm diameter circular areas were demarcated to serve as normal skin controls. Wounds were assessed at post-burn days 3, 7, 14, 21, 28, 60 and 90 with a variety of non-invasive imaging and punch biopsies. Treatments were re-applied at each assessment. The primary outcome was the amount of wound re-epithelialization, measured histologically, at post-burn day 28. Secondary outcomes consisted of the percentage of wound contraction, amount of superficial blood flow, and mean bacterial load. RESULTS: The amount of wound re-epithelialization in wounds treated with SPM was 96% whereas those treated with the SOC measured only slightly less at 92% (p = 0.56). The percentage of wound contraction was 39% in the SPM with gentamicin group, while in the SOC group contraction was higher at 45% (p = 0.20). Moreover, superficial blood flow in the SPM group was measured to be 168% of normal skin controls, while wounds in the SPM with gentamicin group were slightly lower at 160%, and in wounds treated with the SOC blood flow was 110% of normal skin controls (p = 0.27). The mean bacterial load in each group was measured at post-burn day 3 and notably consisted of bacterial load being the lowest in wounds treated with gentamicin alone at 17/100, meanwhile in wounds treated with the SOC or those in the SPM with gentamicin group, mean bacterial loads were significantly higher at 43/100 and 47/100, respectively (p = 0.02). CONCLUSIONS: SPM applied to deep partial-thickness burns did not significantly improve measured outcomes over the SOC. Although numerical improvements were shown in all measured outcomes, no significant differences were noted. The theoretical and observed potential for SPM to improve wound healing deserves additional evaluation in larger preclinical studies.
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spelling pubmed-89462032022-03-28 810 Synthetic Platelet-Mimetics with Gentamicin: Outcomes in Deep Partial-Thickness Burns Valdera, Franklin Nuutila, Kristo Cooper, Laura E Varon, David E Cooley, Jennifer Chapa, Javier Chan, Rodney K Carlsson, Anders H J Burn Care Res Translational Sciences: Wounds & Scars 2 INTRODUCTION: Infection and prolonged inflammation in deep partial-thickness burns can lead to inadequate healing. In addition to their role in hemostasis, activated platelets also contain granules with anti-inflammatory properties which may impact wound healing. However, portability and storage of platelets remain a challenge. Synthetic platelet-mimetics (SPM) avoid these difficulties, but like natural platelets, SPM have vesicles that can transport bioactive agents, such as antibiotics. We sought to evaluate wound healing outcomes in deep partial-thickness burns treated topically with SPM. METHODS: A total of 30 circular, deep partial-thickness burns were created on the dorsum of 2 porcine models. Each wound measured 5cm in diameter and was standardized using a thermocoupled burn device. Sets of six wounds were randomized into five groups: SPM, gentamicin alone, SPM with gentamicin, a vehicle control (saline), or dry gauze (the standard of care, SOC). Additionally, two separate 5cm diameter circular areas were demarcated to serve as normal skin controls. Wounds were assessed at post-burn days 3, 7, 14, 21, 28, 60 and 90 with a variety of non-invasive imaging and punch biopsies. Treatments were re-applied at each assessment. The primary outcome was the amount of wound re-epithelialization, measured histologically, at post-burn day 28. Secondary outcomes consisted of the percentage of wound contraction, amount of superficial blood flow, and mean bacterial load. RESULTS: The amount of wound re-epithelialization in wounds treated with SPM was 96% whereas those treated with the SOC measured only slightly less at 92% (p = 0.56). The percentage of wound contraction was 39% in the SPM with gentamicin group, while in the SOC group contraction was higher at 45% (p = 0.20). Moreover, superficial blood flow in the SPM group was measured to be 168% of normal skin controls, while wounds in the SPM with gentamicin group were slightly lower at 160%, and in wounds treated with the SOC blood flow was 110% of normal skin controls (p = 0.27). The mean bacterial load in each group was measured at post-burn day 3 and notably consisted of bacterial load being the lowest in wounds treated with gentamicin alone at 17/100, meanwhile in wounds treated with the SOC or those in the SPM with gentamicin group, mean bacterial loads were significantly higher at 43/100 and 47/100, respectively (p = 0.02). CONCLUSIONS: SPM applied to deep partial-thickness burns did not significantly improve measured outcomes over the SOC. Although numerical improvements were shown in all measured outcomes, no significant differences were noted. The theoretical and observed potential for SPM to improve wound healing deserves additional evaluation in larger preclinical studies. Oxford University Press 2022-03-23 /pmc/articles/PMC8946203/ http://dx.doi.org/10.1093/jbcr/irac012.358 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Translational Sciences: Wounds & Scars 2
Valdera, Franklin
Nuutila, Kristo
Cooper, Laura E
Varon, David E
Cooley, Jennifer
Chapa, Javier
Chan, Rodney K
Carlsson, Anders H
810 Synthetic Platelet-Mimetics with Gentamicin: Outcomes in Deep Partial-Thickness Burns
title 810 Synthetic Platelet-Mimetics with Gentamicin: Outcomes in Deep Partial-Thickness Burns
title_full 810 Synthetic Platelet-Mimetics with Gentamicin: Outcomes in Deep Partial-Thickness Burns
title_fullStr 810 Synthetic Platelet-Mimetics with Gentamicin: Outcomes in Deep Partial-Thickness Burns
title_full_unstemmed 810 Synthetic Platelet-Mimetics with Gentamicin: Outcomes in Deep Partial-Thickness Burns
title_short 810 Synthetic Platelet-Mimetics with Gentamicin: Outcomes in Deep Partial-Thickness Burns
title_sort 810 synthetic platelet-mimetics with gentamicin: outcomes in deep partial-thickness burns
topic Translational Sciences: Wounds & Scars 2
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946203/
http://dx.doi.org/10.1093/jbcr/irac012.358
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