Molecular Medicine

, Volume 13, Issue 1–2, pp 30–39 | Cite as

Molecular Markers in Patients with Chronic Wounds to Guide Surgical Debridement

  • Harold Brem
  • Olivera Stojadinovic
  • Robert F. Diegelmann
  • Hyacinth Entero
  • Brian Lee
  • Irena Pastar
  • Michael Golinko
  • Harvey Rosenberg
  • Marjana Tomic-Canic
Research Article


Chronic wounds, such as venous ulcers, are characterized by physiological impairments manifested by delays in healing, resulting in severe morbidity. Surgical debridement is routinely performed on chronic wounds because it stimulates healing. However, procedures are repeated many times on the same patient because, in contrast to tumor excision, there are no objective biological/molecular markers to guide the extent of debridement. To develop bioassays that can potentially guide surgical debridement, we assessed the pathogenesis of the patients’ wound tissue before and after wound debridement. We obtained biopsies from three patients at two locations, the nonhealing edge (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers (post debridement), and evaluated their histology, biological response to wounding (migration) and gene expression profile. We found that biopsies from the nonhealing edges exhibit distinct pathogenic morphology (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased procollagen synthesis). Fibroblasts deriving from this location exhibit impaired migration in comparison to the cells from adjacent nonulcerated biopsies, which exhibit normalization of morphology and normal migration capacity. The nonhealing edges have a specific, identifiable, and reproducible gene expression profile. The adjacent nonulcerated biopsies have their own distinctive reproducible gene expression profile, signifying that particular wound areas can be identified by gene expression profiling. We conclude that chronic ulcers contain distinct subpopulations of cells with different capacity to heal and that gene expression profiling can be utilized to identify them. In the future, molecular markers will be developed to identify the nonimpaired tissue, thereby making surgical debridement more accurate and more efficacious.



Special thanks to Dr H. Paul Ehrlich, Dr Stephen Dotty, and members of HSS histology core for their assistance in histology analyses. Our research is supported by the National Institutes of Health grants DK59424 (HB), LM008443 (HB), AR45974 (MT-C), NR08029 (MT-C), and the VCU A D Williams Foundation (RFD). We also acknowledge the use of The Musculoskeletal Repair and Regeneration Core Center of HSS (AR046121).


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Copyright information

© Feinstein Institute for Medical Research 2007

Authors and Affiliations

  • Harold Brem
    • 1
  • Olivera Stojadinovic
    • 2
  • Robert F. Diegelmann
    • 3
  • Hyacinth Entero
    • 1
    • 4
  • Brian Lee
    • 5
  • Irena Pastar
    • 2
  • Michael Golinko
    • 1
  • Harvey Rosenberg
    • 1
  • Marjana Tomic-Canic
    • 2
  1. 1.Department of Surgery, Wound Healing and Vascular Biology LaboratoryColumbia University College of Physicians and SurgeonsNew YorkUSA
  2. 2.Tissue Repair Lab, Tissue Engineering, Regeneration and Repair ProgramHospital for Special Surgery of the Weill Cornell College of MedicineNew YorkUSA
  3. 3.Department of BiochemistryVirginia Commonwealth UniversityRichmondUSA
  4. 4.Ross University School of MedicineRoseauCommonwealth of Dominica
  5. 5.GenentechSan FranciscoUSA

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