Three-dimensional human tissue models that incorporate diabetic foot ulcer-derived fibroblasts mimic in vivo features of chronic wounds

Anna G. Maione, Yevgeny Brudno, Olivera Stojadinovic, Lara K. Park, Avi Smith, Ana Tellechea, Ermelindo C. Leal, Cathal J. Kearney, Aristidis Veves, Marjana Tomic-Canic, David J. Mooney, Jonathan A. Garlick

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Diabetic foot ulcers (DFU) are a major, debilitating complication of diabetes mellitus. Unfortunately, many DFUs are refractory to existing treatments and frequently lead to amputation. The development of more effective therapies has been hampered by the lack of predictive in vitro methods to investigate the mechanisms underlying impaired healing. To address this need for realistic wound-healing models, we established patient-derived fibroblasts from DFUs and site-matched controls and used them to construct three-dimensional (3D) models of chronic wound healing. Incorporation of DFU-derived fibroblasts into these models accurately recapitulated the following key aspects of chronic ulcers: reduced stimulation of angiogenesis, increased keratinocyte proliferation, decreased re-epithelialization, and impaired extracellular matrix deposition. In addition to reflecting clinical attributes of DFUs, the wound-healing potential of DFU fibroblasts demonstrated in this suite of models correlated with in vivo wound closure in mice. Thus, the reported panel of 3D DFU models provides a more biologically relevant platform for elucidating the cell-cell and cell-matrix-related mechanisms responsible for chronic wound pathogenesis and may improve translation of in vitro findings into efficacious clinical applications.

Original languageEnglish (US)
Pages (from-to)499-508
Number of pages10
JournalTissue Engineering - Part C: Methods
Volume21
Issue number5
DOIs
StatePublished - May 1 2015

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Three-dimensional human tissue models that incorporate diabetic foot ulcer-derived fibroblasts mimic in vivo features of chronic wounds'. Together they form a unique fingerprint.

  • Cite this

    Maione, A. G., Brudno, Y., Stojadinovic, O., Park, L. K., Smith, A., Tellechea, A., Leal, E. C., Kearney, C. J., Veves, A., Tomic-Canic, M., Mooney, D. J., & Garlick, J. A. (2015). Three-dimensional human tissue models that incorporate diabetic foot ulcer-derived fibroblasts mimic in vivo features of chronic wounds. Tissue Engineering - Part C: Methods, 21(5), 499-508. https://doi.org/10.1089/ten.tec.2014.0414