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: Joseph T Hardwicke, Jeff Hart, Andrea Bell, Ruth Duncan, David W Thomas, Ryan Moseley
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 152 Issue 3 Pg. 411-7 (Jun 30 2011) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 21435363 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Dextrins
• Drug Carriers
• Recombinant Proteins
• Epidermal Growth Factor
• alpha-Amylases

Topics

• Animals
• Dextrins (chemistry)
• Diabetes Complications (drug therapy, pathology)
• Drug Carriers (chemistry)
• Epidermal Growth Factor (administration & dosage, blood, chemistry, pharmacology, therapeutic use)
• Granulation Tissue (anatomy & histology, blood supply, drug effects, growth & development)
• Humans
• Male
• Mice
• Mice, Mutant Strains
• Neovascularization, Physiologic (drug effects)
• Recombinant Proteins (administration & dosage, blood, chemistry, pharmacology, therapeutic use)
• Skin (drug effects, pathology)
• Wound Healing (drug effects)
• alpha-Amylases (blood)