title: Use of a fibrin-based system for enhancing angiogenesis and modulating inflammation in the treatment of hyperglycemic wounds.
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.
authors: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
authors: M
authors: M
authors: Kulkarni
authors: Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.
authors: A
authors: A
authors: O'Loughlin
authors: Department 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.
authors: R
authors: R
authors: Vazquez
authors: Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.
authors: K
authors: K
authors: Mashayekhi
authors: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
authors: P
authors: P
authors: Rooney
authors: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland; Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.
authors: U
authors: U
authors: Greiser
authors: Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors: E
authors: E
authors: O'Toole
authors: Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.
authors: T
authors: T
authors: O'Brien
authors: Department 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.
authors: Maria M
authors: MM
authors: Malagon
authors: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland. Electronic address: abhay.pandit@nuigalway.ie.
authors: A
authors: A
authors: Pandit
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005337:Fibrin / Q000737:chemistry*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011817:Rabbits; D014945:Wound Healing / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D005337:Fibrin; D052250:Nitric Oxide Synthase Type III; D020691:rab GTP-Binding Proteins
keywords: Angiogenesis; Diabetes; Gene therapy; Inflammation; Keratinocyte; Wound healing