The Impact of Prolonged Inflammation on Wound Healing
The treatment of chronic wounds still challenges modern medicine because of these wounds’ heterogenic pathophysiology. Processes such as inflammation, ischemia and bacterial infection play major roles in the progression of a chronic wound. In recent years, preclinical wound models have been used to...
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MDPI AG
2022-04-01
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Online Access: | https://www.mdpi.com/2227-9059/10/4/856 |
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author | Judith C. J. Holzer-Geissler Simon Schwingenschuh Martin Zacharias Johanna Einsiedler Sonja Kainz Peter Reisenegger Christian Holecek Elisabeth Hofmann Barbara Wolff-Winiski Hermann Fahrngruber Thomas Birngruber Lars-Peter Kamolz Petra Kotzbeck |
author_facet | Judith C. J. Holzer-Geissler Simon Schwingenschuh Martin Zacharias Johanna Einsiedler Sonja Kainz Peter Reisenegger Christian Holecek Elisabeth Hofmann Barbara Wolff-Winiski Hermann Fahrngruber Thomas Birngruber Lars-Peter Kamolz Petra Kotzbeck |
author_sort | Judith C. J. Holzer-Geissler |
collection | DOAJ |
description | The treatment of chronic wounds still challenges modern medicine because of these wounds’ heterogenic pathophysiology. Processes such as inflammation, ischemia and bacterial infection play major roles in the progression of a chronic wound. In recent years, preclinical wound models have been used to understand the underlying processes of chronic wound formation. However, the wound models used to investigate chronic wounds often lack translatability from preclinical models to patients, and often do not take exaggerated inflammation into consideration. Therefore, we aimed to investigate prolonged inflammation in a porcine wound model by using resiquimod, a TLR7 and TLR8 agonist. Pigs received full thickness excisional wounds, where resiquimod was applied daily for 6 days, and untreated wounds served as controls. Dressing change, visual documentation and wound scoring were performed daily. Biopsies were collected for histological as well as gene expression analysis. Resiquimod application on full thickness wounds induced a visible inflammation of wounds, resulting in delayed wound healing compared to non-treated control wounds. Gene expression analysis revealed high levels of IL6, MMP1 and CD68 expression after resiquimod application, and histological analysis showed increased immune cell infiltration. By using resiquimod, we were able to show that prolonged inflammation delayed wound healing, which is often observed in chronic wounds in patients. The model we used shows the importance of inflammation in wound healing and gives an insight into the progression of chronic wounds. |
first_indexed | 2024-03-09T11:06:43Z |
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issn | 2227-9059 |
language | English |
last_indexed | 2024-03-09T11:06:43Z |
publishDate | 2022-04-01 |
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series | Biomedicines |
spelling | doaj.art-0adb736ea2344004badd2ae3ce9c9c282023-12-01T00:54:24ZengMDPI AGBiomedicines2227-90592022-04-0110485610.3390/biomedicines10040856The Impact of Prolonged Inflammation on Wound HealingJudith C. J. Holzer-Geissler0Simon Schwingenschuh1Martin Zacharias2Johanna Einsiedler3Sonja Kainz4Peter Reisenegger5Christian Holecek6Elisabeth Hofmann7Barbara Wolff-Winiski8Hermann Fahrngruber9Thomas Birngruber10Lars-Peter Kamolz11Petra Kotzbeck12Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaHEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, AustriaDiagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, AustriaCOREMED-Cooperative Centre for Regenerative Medicine, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, AustriaHEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, AustriaHEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, AustriaHEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, AustriaResearch Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaAKRIBES Biomedical GmbH, 1030 Vienna, AustriaAKRIBES Biomedical GmbH, 1030 Vienna, AustriaHEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, AustriaResearch Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaResearch Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaThe treatment of chronic wounds still challenges modern medicine because of these wounds’ heterogenic pathophysiology. Processes such as inflammation, ischemia and bacterial infection play major roles in the progression of a chronic wound. In recent years, preclinical wound models have been used to understand the underlying processes of chronic wound formation. However, the wound models used to investigate chronic wounds often lack translatability from preclinical models to patients, and often do not take exaggerated inflammation into consideration. Therefore, we aimed to investigate prolonged inflammation in a porcine wound model by using resiquimod, a TLR7 and TLR8 agonist. Pigs received full thickness excisional wounds, where resiquimod was applied daily for 6 days, and untreated wounds served as controls. Dressing change, visual documentation and wound scoring were performed daily. Biopsies were collected for histological as well as gene expression analysis. Resiquimod application on full thickness wounds induced a visible inflammation of wounds, resulting in delayed wound healing compared to non-treated control wounds. Gene expression analysis revealed high levels of IL6, MMP1 and CD68 expression after resiquimod application, and histological analysis showed increased immune cell infiltration. By using resiquimod, we were able to show that prolonged inflammation delayed wound healing, which is often observed in chronic wounds in patients. The model we used shows the importance of inflammation in wound healing and gives an insight into the progression of chronic wounds.https://www.mdpi.com/2227-9059/10/4/856prolonged inflammationwound healinginflammationresiquimod R848wound model |
spellingShingle | Judith C. J. Holzer-Geissler Simon Schwingenschuh Martin Zacharias Johanna Einsiedler Sonja Kainz Peter Reisenegger Christian Holecek Elisabeth Hofmann Barbara Wolff-Winiski Hermann Fahrngruber Thomas Birngruber Lars-Peter Kamolz Petra Kotzbeck The Impact of Prolonged Inflammation on Wound Healing Biomedicines prolonged inflammation wound healing inflammation resiquimod R848 wound model |
title | The Impact of Prolonged Inflammation on Wound Healing |
title_full | The Impact of Prolonged Inflammation on Wound Healing |
title_fullStr | The Impact of Prolonged Inflammation on Wound Healing |
title_full_unstemmed | The Impact of Prolonged Inflammation on Wound Healing |
title_short | The Impact of Prolonged Inflammation on Wound Healing |
title_sort | impact of prolonged inflammation on wound healing |
topic | prolonged inflammation wound healing inflammation resiquimod R848 wound model |
url | https://www.mdpi.com/2227-9059/10/4/856 |
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