Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Nischwitz, S.
Local alterations in scars OR Contributing factors to hypertrophic scar formation – implementation of a novel Duroc pig model
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp. 137
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Kamolz Lars-Peter
- Spendel Stephan
- Altmetrics:
- Abstract:
- Background: Hypertrophic scarring still poses a major challenge, especially after burns. Most treatment modalities lack evidence, not least because the pathophysiology is incompletely understood. A persistent inflammatory response throughout the healing process appears to be the triggering factor in pathologic scarring. To properly understand pathophysiology in heterogeneous phenomena like scars, models are required. Many scar models exist, but the Duroc pig has emerged as one with similar hypertrophic scars to humans. This project's objectives were to investigate the mechanisms of scar formation following prolonged inflammation, observe differences in various scar etiologies, and to introduce a method for creating standardized hypertrophic scars by induction of prolonged inflammation. Methods: Four distinct wound types were inflicted on the backs of six Duroc pigs: excisional full-thickness and burn wounds, and versions of both of these that had an additional inflammation boost induced by resiquimod for six days. Throughout the subsequent five months, clinical evaluation by scores and imaging, tissue oxygenation as measured by hyperspectral imaging, histologic assessment, and gene expression analyses were carried out at several different time points. Results: All four wound types resulted in distinct scars. Burn wounds, and both types of induced wounds resulted in significantly higher scar scores. The induction by resiquimod mimicked the inflammatory response after burns in both induced wound types and subsided slightly earlier in excisional wounds than in burn wounds. Relative hypoxia was seen in all three wound types as compared to full-thickness wounds in hyperspectral imaging. Gene expression analysis confirmed these hypoxic conditions but revealed only low alterations concerning remodeling parameters. Hypoxia in early wound stages correlated with the final scar score; this correlation was also shown for inflammation during wound healing, but lower. Resiquimod-induced full-thickness wounds showed the highest number of inflammatory cells and the histologic hallmarks of hypertrophic scars, similar to both types of burn wounds. Conclusion: Various wound etiologies on the Duroc pig were used to find local alterations in scars. We successfully created a new model for hypertrophic scarring. Increased inflammation and hypoxia caused by burns and resiquimod resulted in more severe scars. Future studies are needed to further investigate the exact pathophysiology of pathologic scarring and to advance the model for preclinical testing.