2. Academic Validation
  3. Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics

Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics

  • J Invest Dermatol. 2025 Mar;145(3):631-644.e22. doi: 10.1016/j.jid.2024.05.029.
Petra Doerfler 1,  Nicole Schoefmann 2,  Gabriela Cabral 2,  Wolfgang Bauer 3,  Martin C Berli 4,  Barbara Binder 5,  Carina Borst 3,  Sander Botter 6,  Lars E French 7,  Tobias Goerge 8,  Juerg Hafner 9,  Daniela Hartmann 7,  Annette Høgh 10,  Wolfram Hoetzenecker 11,  Judith C J Holzer-Geissler 12,  Lars P Kamolz 12,  Katrin Kofler 13,  Thomas Luger 8,  Sebastian P Nischwitz 12,  Michael Popovits 14,  Klemens Rappersberger 15,  Gaetana Restivo 9,  Justin G Schlager 7,  Matthias Schmuth 16,  Georg Stingl 3,  Theresa Stockinger 15,  Anke Stroelin 13,  Anton Stuetz 2,  Julian Umlauft 17,  Wolfgang P Weninger 3,  Barbara Wolff-Winiski 18
Affiliations

Affiliations

  • 1 Akribes Biomedical GmbH, Vienna, Austria. Electronic address: [email protected].
  • 2 Akribes Biomedical GmbH, Vienna, Austria.
  • 3 Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • 4 Balgrist University Hospital, Zurich, Switzerland; Technical Orthopedics, Diabetic Foot Consultation, Wound Outpatient Clinic, Spital Limmattal, Schlieren, Switzerland.
  • 5 Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria.
  • 6 Swiss Center for Musculoskeletal Biobanking, Balgrist Campus AG, Zurich, Switzerland.
  • 7 Department of Dermatology and Allergology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
  • 8 Department of Dermatology, University of Münster, Muenster, Germany.
  • 9 Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
  • 10 Department of Vascular Surgery, Regionshospitalet Viborg, Viborg, Denmark.
  • 11 Department of Dermatology and Venerology, University of Linz, Linz, Austria.
  • 12 Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria.
  • 13 Department of Dermatology, Medical University of Tübingen, Tuebingen, Germany.
  • 14 Department of Surgery, Barmherzige Brueder Hospital Graz, Graz, Austria; Privatklinik Graz Ragnitz, Graz, Austria.
  • 15 Klinik Landstrasse, Vienna, Austria.
  • 16 Department of Dermatology, Venerology and Allergology, Medical University of Innsbruck, Innsbruck, Austria.
  • 17 Department of Dermatology, Venerology and Allergology, Medical University of Innsbruck, Innsbruck, Austria; Dermatology, Zellmed Medalp, Zell am Ziller, Austria.
  • 18 Akribes Biomedical GmbH, Vienna, Austria. Electronic address: [email protected].
PMID: 38960086 DOI: 10.1016/j.jid.2024.05.029
Abstract

Exudates of nonhealing wounds contain drivers of pathogenicity. We utilized >800 exudates from nonhealing and healing wounds of diverse etiologies, collected by 3 different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to (i) differentiate between healing and nonhealing wounds, (ii) follow the healing process of individual patients, and (iii) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically nonhealing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo nonhealing wound exudates revealed an induction of inflammatory cytokine and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of nonhealing wounds. Testing the wound therapeutics, PDGF and silver sulfadiazine, yielded responses in line with clinical experience and indicates the usefulness of the assay to search for and profile new therapeutics.

Keywords

Biomarker; Functional assay; Transcriptomics; Wound exudate; Wound healing.

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