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Biomaterials. 2014 Feb;35(6):2001-10. doi: 10.1016/j.biomaterials.2013.11.003. Epub 2013 Dec 10.

Use of a fibrin-based system for enhancing angiogenesis and modulating inflammation in the treatment of hyperglycemic wounds.

Author information

  • 1Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
  • 2Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.
  • 3Department of Cell Biology, Physiology, and Immunology, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, 14014-Cordoba, Spain.
  • 4Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland; Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.
  • 5Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • 6Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland. Electronic address: abhay.pandit@nuigalway.ie.

Abstract

The complex pathophysiology of chronic ulceration in diabetic patients is poorly understood; diabetes-related lower limb amputation is a major health issue, which has limited effective treatment regimes in the clinic. This study attempted to understand the complex pathology of hyperglycemic wound healing by showing profound changes in gene expression profiles in wounded human keratinocytes in hyperglycemic conditions compared to normal glucose conditions. In the hyper-secretory wound microenvironment of hyperglycemia, Rab18, a secretory control molecule, was found to be significantly downregulated. Using a biomaterial platform for dual therapy targeting the two distinct pathways, this study aimed to resolve the major dysregulated pathways in hyperglycemic wound healing. To complement Rab18, and promote angiogenesis eNOS was also targeted, and this novel Rab18-eNOS therapy via a dynamically controlled 'fibrin-in-fibrin' delivery system, demonstrated enhanced wound closure, by increasing functional angiogenesis and reducing inflammation, in an alloxan-induced hyperglycemic preclinical ear ulcer model of compromised wound healing.

Copyright © 2013 Elsevier Ltd. All rights reserved.

KEYWORDS:

Angiogenesis; Diabetes; Gene therapy; Inflammation; Keratinocyte; Wound healing

PMID:
24331702
[PubMed - in process]
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