The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars—A New Model in the Duroc Pig
Hypertrophic scars continue to be a major burden, especially after burns. Persistent inflammation during wound healing appears to be the precipitating aspect in pathologic scarring. The lack of a standardized model hinders research from fully elucidating pathophysiology and therapy, as most therapeu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/316 |
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| author | Sebastian P. Nischwitz Julia Fink Marlies Schellnegger Hanna Luze Vladimir Bubalo Carolin Tetyczka Eva Roblegg Christian Holecek Martin Zacharias Lars-Peter Kamolz Petra Kotzbeck |
| author_facet | Sebastian P. Nischwitz Julia Fink Marlies Schellnegger Hanna Luze Vladimir Bubalo Carolin Tetyczka Eva Roblegg Christian Holecek Martin Zacharias Lars-Peter Kamolz Petra Kotzbeck |
| author_sort | Sebastian P. Nischwitz |
| collection | DOAJ |
| description | Hypertrophic scars continue to be a major burden, especially after burns. Persistent inflammation during wound healing appears to be the precipitating aspect in pathologic scarring. The lack of a standardized model hinders research from fully elucidating pathophysiology and therapy, as most therapeutic approaches have sparse evidence. The goal of this project was to investigate the mechanisms of scar formation after prolonged wound inflammation and to introduce a method for generating standardized hypertrophic scars by inducing prolonged inflammation. Four wound types were created in Duroc pigs: full-thickness wounds, burn wounds, and both of them with induced hyperinflammation by resiquimod. Clinical assessment (Vancouver Scar Scale), tissue oxygenation by hyperspectral imaging, histologic assessment, and gene expression analysis were performed at various time points during the following five months. Native burn wounds as well as resiquimod-induced full-thickness and burn wounds resulted in more hypertrophic scars than full-thickness wounds. The scar scale showed significantly higher scores in burn- and resiquimod-induced wounds compared with full-thickness wounds as of day 77. These three wound types also showed relative hypoxia compared with uninduced full-thickness wounds in hyperspectral imaging and increased expression of <i>HIF1a</i> levels. The highest number of inflammatory cells was detected in resiquimod-induced full-thickness wounds with histologic features of hypertrophic scars in burn and resiquimod-induced wounds. Gene expression analysis revealed increased inflammation with only moderately altered fibrosis markers. We successfully created hypertrophic scars in the Duroc pig by using different wound etiologies. Inflammation caused by burns or resiquimod induction led to scars similar to human hypertrophic scars. This model may allow for the further investigation of the exact mechanisms of pathological scars, the role of hypoxia and inflammation, and the testing of therapeutic approaches. |
| first_indexed | 2024-03-11T10:00:03Z |
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| id | doaj.art-a099d681901b4f719d23c6f6b16ad978 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T10:00:03Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a099d681901b4f719d23c6f6b16ad9782023-11-16T15:31:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124131610.3390/ijms24010316The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars—A New Model in the Duroc PigSebastian P. Nischwitz0Julia Fink1Marlies Schellnegger2Hanna Luze3Vladimir Bubalo4Carolin Tetyczka5Eva Roblegg6Christian Holecek7Martin Zacharias8Lars-Peter Kamolz9Petra Kotzbeck10Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaCOREMED—Cooperative Centre for Regenerative Medicine, JOANNEUM RESEARCH Forschungsgesellschaft mbH, 8010 Graz, AustriaDivision of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaDivision of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaBiomedical Research Unit, Medical University of Graz, 8036 Graz, AustriaDepartment of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, AustriaDepartment of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, AustriaHEALTH—Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, 8010 Graz, AustriaDiagnostic and Research Institute of Pathology, Medical University of Graz, 8036 Graz, AustriaDivision of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaDivision of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaHypertrophic scars continue to be a major burden, especially after burns. Persistent inflammation during wound healing appears to be the precipitating aspect in pathologic scarring. The lack of a standardized model hinders research from fully elucidating pathophysiology and therapy, as most therapeutic approaches have sparse evidence. The goal of this project was to investigate the mechanisms of scar formation after prolonged wound inflammation and to introduce a method for generating standardized hypertrophic scars by inducing prolonged inflammation. Four wound types were created in Duroc pigs: full-thickness wounds, burn wounds, and both of them with induced hyperinflammation by resiquimod. Clinical assessment (Vancouver Scar Scale), tissue oxygenation by hyperspectral imaging, histologic assessment, and gene expression analysis were performed at various time points during the following five months. Native burn wounds as well as resiquimod-induced full-thickness and burn wounds resulted in more hypertrophic scars than full-thickness wounds. The scar scale showed significantly higher scores in burn- and resiquimod-induced wounds compared with full-thickness wounds as of day 77. These three wound types also showed relative hypoxia compared with uninduced full-thickness wounds in hyperspectral imaging and increased expression of <i>HIF1a</i> levels. The highest number of inflammatory cells was detected in resiquimod-induced full-thickness wounds with histologic features of hypertrophic scars in burn and resiquimod-induced wounds. Gene expression analysis revealed increased inflammation with only moderately altered fibrosis markers. We successfully created hypertrophic scars in the Duroc pig by using different wound etiologies. Inflammation caused by burns or resiquimod induction led to scars similar to human hypertrophic scars. This model may allow for the further investigation of the exact mechanisms of pathological scars, the role of hypoxia and inflammation, and the testing of therapeutic approaches.https://www.mdpi.com/1422-0067/24/1/316hypertrophic scarfibrosisanimal modelinflammationhypoxiaDuroc pig |
| spellingShingle | Sebastian P. Nischwitz Julia Fink Marlies Schellnegger Hanna Luze Vladimir Bubalo Carolin Tetyczka Eva Roblegg Christian Holecek Martin Zacharias Lars-Peter Kamolz Petra Kotzbeck The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars—A New Model in the Duroc Pig International Journal of Molecular Sciences hypertrophic scar fibrosis animal model inflammation hypoxia Duroc pig |
| title | The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars—A New Model in the Duroc Pig |
| title_full | The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars—A New Model in the Duroc Pig |
| title_fullStr | The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars—A New Model in the Duroc Pig |
| title_full_unstemmed | The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars—A New Model in the Duroc Pig |
| title_short | The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars—A New Model in the Duroc Pig |
| title_sort | role of local inflammation and hypoxia in the formation of hypertrophic scars a new model in the duroc pig |
| topic | hypertrophic scar fibrosis animal model inflammation hypoxia Duroc pig |
| url | https://www.mdpi.com/1422-0067/24/1/316 |
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