title: The effect of dextrin-rhEGF on the healing of full-thickness, excisional wounds in the (db/db) diabetic mouse.
abstract: Chronic wounds, such as ulceration of the lower limb, represent a significant clinical challenge in today's ageing society. With the aim of identifying improved therapeutics, we have previously described a bioresponsive, dextrin-recombinant human epidermal growth factor conjugate (dextrin-rhEGF), that (i) protects rhEGF against proteolytic degradation by human chronic wound fluid; and (ii) mediates rhEGF release by α-amylase, capable of stimulating increased proliferation/migration in normal dermal and chronic wound fibroblasts; and keratinocytes, in vitro. The aim of this study was to extend these findings, by investigating the effects of dextrin-rhEGF on wound healing in the (db/db) diabetic mouse, a widely used in vivo model of delayed wound healing. Standardised, full-thickness excisional wounds, created in the dorsal flank skin, were treated topically with succinoylated dextrin (50 μg/mL), rhEGF (10 μg/mL) or dextrin-rhEGF (1 or 10 μg/mL). Treatments were applied immediately after injury and subsequently on post-wounding, days 3 and 8. Wound healing was assessed macroscopically, in terms of initiation of neo-dermal tissue deposition and wound closure (including wound contraction and re-epithelialisation), over a 16 day period. Wound healing was assessed histologically, in terms of granulation tissue formation/maturity; cranio-caudal wound contraction and wound angiogenesis (CD31 immuno-staining), using tissues harvested at day 16. Blood samples were also analysed for α-amylase and rhEGF concentrations. In this established impaired wound healing model, the topically-applied dextrin-rhEGF significantly accelerated wound closure and neo-dermal tissue formation at the macroscopic level; and significantly increased granulation tissue deposition and angiogenesis at the histological level (p<0.05), relative to untreated, succinoylated dextrin and rhEGF alone controls. Overall, these findings support the further development of bioresponsive polymer conjugates, for tissue repair.
authors: Wound Biology Group, Cardiff Institute of Tissue Engineering and Repair (CITER), Tissue Engineering and Reparative Dentistry, School of Dentistry, Cardiff University, Heath Park, UK.
authors: Joseph T
authors: JT
authors: Hardwicke
authors: Jeff
authors: J
authors: Hart
authors: Andrea
authors: A
authors: Bell
authors: Ruth
authors: R
authors: Duncan
authors: David W
authors: DW
authors: Thomas
authors: Ryan
authors: R
authors: Moseley
mesh_terms: D000818:Animals; D003912:Dextrins / Q000737:chemistry*; D048909:Diabetes Complications / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006097:Granulation Tissue / Q000033:anatomy & histology / Q000098:blood supply / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*; D000516:alpha-Amylases / Q000097:blood
chemical_list: D003912:Dextrins; D004337:Drug Carriers; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D000516:alpha-Amylases