Researchers presenting at EADV said they believed their findings are a ‘significant step forward in understanding the complex biology of wound healing’.
New research presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024 has identified new targets for wound healing.
The key molecular targets could significantly enhance the healing of both acute and chronic wounds, according to Dr Marta Bertolini, lead author of the study and managing director of QIMA Monasterium, GmbH, Münster, Germany.
“While we must be cautious when discussing synergistic effects, our preliminary data reveal that combinatorial therapy may be a valid option for treating chronic wounds,” she said.
“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.”
Globally, acute and chronic wounds affect nearly one billion people and have a substantial economic burden on healthcare systems.
The researchers’ study involved using healthy full-thickness human skin punches, creating central, partial wounds. These samples were then 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 researchers monitored gene expression changes over a five-day period.
The results revealed several critical differences in gene activity between acute and chronic wounds. Key wound repair-associated genes such as KRT6A-C, PTX3, KRT1, KRT10, COL1A1, along with pathways including Wnt signalling and actin cytoskeleton organisation, were differentially regulated between acute and chronic wounds.
Additionally, overall gene expression was downregulated in chronic wounds compared to acute wounds, suggesting that essential genes required for effective wound healing are inadequately transcribed in these conditions.
Notably, FGF7, a key promoter of epithelial cell proliferation and tissue repair was significantly downregulated in chronic wounds by day five.
In contrast, MMP10, a tissue-degrading enzyme, was elevated throughout the study period in chronic wounds. To counteract these imbalances, the researchers tested the effects of recombinant FGF7 protein and an MMP10-neutralising antibody (α-MMP10) on acute and chronic wounds in the ex vivo wound models.
Topical administration of α-MMP10 led to a significant increase in wound tongue length, indicating improved healing in acute wounds. In contrast, FGF7 did not show a significant effect on its own.
The combined application of FGF7 and α-MMP10, however, significantly enhanced re-epithelisation in both types of wounds.
The study also identified osteopontin (SPP1) as a gene significantly upregulated on days three and five in acute wounds compared to chronic wounds.
To leverage this finding, the researchers administered FOL005, an osteopontin-derived peptide, to experimentally induced wounds ex vivo.
They found treatment with FOL005 significantly enhanced skin re-epithelisation under both physiological and pathological conditions, highlighting its potential as an effective therapeutic option for acute and chronic wound management.
“We believe these findings mark a significant step forward in understanding the complex biology of wound healing,” said Dr Bertolini.
“Our transcriptomic data will soon be accessible, and we hope this will inspire other researchers and industry to identify additional promising targets that could offer much-needed relief to patients affected by these challenging and often debilitating wounds.”
The EADV congress was held in Amsterdam.
