The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars-A New Model in the Duroc Pig.

Autor: Nischwitz SP; Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, Austria.; COREMED-Cooperative Centre for Regenerative Medicine, JOANNEUM RESEARCH Forschungsgesellschaft mbH, 8010 Graz, Austria., Fink J; COREMED-Cooperative Centre for Regenerative Medicine, JOANNEUM RESEARCH Forschungsgesellschaft mbH, 8010 Graz, Austria., Schellnegger M; Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, Austria.; COREMED-Cooperative Centre for Regenerative Medicine, JOANNEUM RESEARCH Forschungsgesellschaft mbH, 8010 Graz, Austria., Luze H; Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, Austria.; COREMED-Cooperative Centre for Regenerative Medicine, JOANNEUM RESEARCH Forschungsgesellschaft mbH, 8010 Graz, Austria., Bubalo V; Biomedical Research Unit, Medical University of Graz, 8036 Graz, Austria., Tetyczka C; Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria., Roblegg E; Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria., Holecek C; HEALTH-Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, 8010 Graz, Austria., Zacharias M; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8036 Graz, Austria., Kamolz LP; Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, Austria.; COREMED-Cooperative Centre for Regenerative Medicine, JOANNEUM RESEARCH Forschungsgesellschaft mbH, 8010 Graz, Austria., Kotzbeck P; Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, Austria.; COREMED-Cooperative Centre for Regenerative Medicine, JOANNEUM RESEARCH Forschungsgesellschaft mbH, 8010 Graz, Austria.; Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, Austria.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Dec 24; Vol. 24 (1). Date of Electronic Publication: 2022 Dec 24.
DOI: 10.3390/ijms24010316
Abstrakt: 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 HIF1a 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.
Databáze: MEDLINE
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