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The effect of dextrin-rhEGF on the healing of full-thickness, excisional wounds in the (db/db) diabetic mouse

Hardwicke, Joseph, Hart, Jeff, Bell, Andrea, Duncan, Ruth, Thomas, David William and Moseley, Ryan 2011. The effect of dextrin-rhEGF on the healing of full-thickness, excisional wounds in the (db/db) diabetic mouse. Journal of Controlled Release 152 (3) , pp. 411-417. 10.1016/j.jconrel.2011.03.016

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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 alpha-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 mu g/mL), rhEGF (10 mu g/mL) or dextrin-rhEGF (1 or 10 mu g/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 alpha-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. (C) 2011 Elsevier B.V. All rights reserved.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Chemistry
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Dextrin-rhEGF conjugate ; Wound repair ; PUMPT,Polymer therapeutics ; Nanomedicine ; (db/db) diabetic mouse ; epidermal-growth-factor ; venous leg ulcers ; polymer therapeutics ; foot ; ulcers ; in-vivo ; acceleration ; formulation ; repair ; mice ; pdgf
Publisher: Elsevier
ISSN: 0168-3659
Last Modified: 04 Apr 2019 23:24
URI: http://orca.cf.ac.uk/id/eprint/15882

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