New targets identified for acute and chronic wound healing

Researchers have identified vital molecular targets using full-thickness human skin punches, potentially reshaping the approach to treating acute and chronic wounds. These discoveries could pave the way for innovative topical therapies to improve the healing of acute and chronic wounds.

Globally, acute and chronic wounds affect nearly one billion people [1]. Chronic wounds severely impact the quality-of-life of those affected, and they pose a substantial economic burden on healthcare systems. “The treatment of chronic wounds is a huge unmet need. This is affecting 1 to 2% of the population,” said Dr Marta Bertolini (QIMA Monasterium GmbH, Germany) [2].

To explore possible innovative wound treatments, Dr Bertolini and colleagues conducted a study using healthy full-thickness human skin according to the punch-in-a-punch wound healing ex vivo wound model. These samples were cultured under either physiological or pathological conditions, including hyperglycaemia, oxidative stress, and hypoxia, to mimic acute and chronic wounds, respectively. Using advanced comparative transcriptomic profiling with bulk RNA sequencing, the team monitored gene expression changes over 5 days.

The results showed several critical differences in gene activity between acute and chronic wounds. Key wound repair-associated genes including KRT6A-C, PTX3, KRT1, KRT10, and COL1A1, and pathways such as Wnt signalling and actin cytoskeleton organisation were differentially regulated between acute and chronic wounds. Moreover, overall gene expression was downregulated in chronic wounds compared with acute wounds, which suggests that essential genes required for effective wound healing are inadequately transcribed in these conditions.

Further, fibroblast growth factor 7 (FGF7), a key promoter of epithelial cell proliferation and tissue repair, was significantly downregulated in chronic wounds by day 5. Conversely, the tissue-degrading enzyme matrix metalloproteinase-10 (MMP10) was elevated throughout the study period in chronic wounds. Topical administration of an MMP10-neutralising antibody (alpha-MMP10) in this wound model improved healing in acute wounds. When this antibody was applied together with FGF7, epithelisation in both acute and chronic wounds was enhanced significantly.

“While we must be cautious when discussing synergistic effects, our preliminary data reveals that combinatorial therapy may be a valid option for the treatment of chronic wounds,” explained Dr Bertolini. “We believe that administering excessive FGF7 promotes epidermal keratinocyte proliferation and mobilisation, which are crucial for wound healing. At the same time, neutralising MMP10 removes a barrier to keratinocyte movement, potentially accelerating re-epithelisation,” she concluded.

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   1. Raziyeva K, et al. Biomolecules 2021;11:700.
   2. Bertolini M. Using comparative transcriptomic profiling ex vivo to identify novel, potential targets for acute and chronic wound healing. FC04.09, EADV Congress 2024, 25–28 September, Amsterdam, the Netherlands.

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Posted on 6 November 20246 November 2024