Wound exudates are considered liquid biopsies of wounds and contain the pathogenic drivers of chronicity. The effects of different types of exudates on healthy primary human dermal fibroblasts (HDF) were investigated, demonstrating growth- and matrix-inhibitory as well as pro-inflammatory effects of chronic wound exudates. To identify potential drugs which could reverse these adverse effects, chemical compounds and growth factors were screened in a proliferation assay. Exudates from healing or chronic venous-, arterial-, mixed-, pressure- and diabetic ulcers, as well as surgical wounds were harvested by negative pressure therapy or using nylon-flocked swabs. HDF from healthy donors were incubated with sterile-filtered exudates diluted in medium in the presence or absence of test proteins or compounds for 72 hours for 2D cultures and 4 – 8 days for 3D cultures. Proliferation and extracellular matrix formation were measured by protein staining. Il-1beta was determined in supernatants, and collagen 1 and -3 mRNAs were measured by RT-PCR. Our studies showed a causal link between wound chronicity and detrimental effects of wound exudates on HDF, both in 2D- and 3D-culture. In over 400 exudates investigated, the positive predictive value of fibroblast growth inhibition for non-healing wound exudates was >85%. Effective concentrations for inhibition (EC50) ranged from 0.3% to 4% of exudate in cell culture medium. The progression of a non-healing to a healing wound in a patient was reflected by our ex vivo assays. Growth factors like PDGF rescued HDF from the inhibitory effects of chronic exudates in < 20% of patient samples, similar to clinical experience. Screening of a library of >2000 compounds in use or in development for other indications revealed compounds with so far unknown wound healing potential. We have developed an assay platform for personalized therapy of chronic wound patients. Based on this platform, we identified compounds with so far unknown potential for the treatment of chronic wounds. Selected compounds will be carried forward to clinical investigations.

ESDR602 - Development of an assay platform for personalized treatment of chronic wounds

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.