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Manchester, United Kingdom

Henderson J.,Norwich University | Ferguson M.W.J.,Renovo Ltd | Terenghi G.,University of Manchester
Journal of Plastic, Reconstructive and Aesthetic Surgery | Year: 2012

Background: Wounds deprived of innervation fail to heal normally, and hypertrophic scars may be abnormally innervated. Manipulation of wounds alters the subsequent degree of scarring, and isoforms of transforming growth factor beta (TGFβ) are well established in this role, whilst TGFβ3 is undergoing clinical trials as an antiscarring agent for clinical use. It is unclear if treated wounds show changes in their innervation patterns as they mature into scars. Methods: Mice underwent 1cm 2 full thickness skin excisions which were treated with TGFβ1 or TGFβ3. Wounds were harvested between 5 and 84 days (n = 6 at each time point). Sections underwent histological scar assessment and immunohistochemical staining for protein gene product 9.5 (PGP9.5), a pan-neuronal marker, and the sensory neuropeptides calcitonin gene related peptide (CGRP) and substance P (SP). Results: There was no difference in the reinnervation pattern between the peripheral and central parts of the wounds. Wounds treated with TGFβ3 healed with dermal collagen organised more like normal skin, whereas TGFβ1 treated wounds had abnormally orientated collagen within the scar compared to control treated wounds. Nerve fibre growth into the wounds followed a similar pattern in control and treated wounds, with only one significant difference during the healing process- at 42 days, the density of nerve fibres immunostained with PGP9.5 within the scar was greater than in control wounds. By 84 days, the density of PGP9.5, CGRP and SP immunopositive fibres were similar in control wounds and those treated with TGFβ isoforms. Conclusions: Changes in reinnervation patterns of wounds treated with TGFβ isoforms were only slightly different from those of control wounds, and by 84 days, the patterns were similar. © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Henderson J.,Norwich University | Henderson J.,University of Manchester | Terenghi G.,University of Manchester | Ferguson M.W.J.,Renovo Ltd
Journal of Anatomy | Year: 2011

Fetal wounds can heal without scarring. There is evidence that the sensory nervous system plays a role in mediating inflammation and healing, and that the reinnervation pattern of adult wounds differs from that of unwounded skin. Ectoderm is required for development of the cutaneous nerve plexus in early gestation. It was hypothesised that scarless fetal wounds might completely regenerate their neural and vascular architecture. Wounds were made on mouse fetuses at embryonic day16.5 of a 19.5-day gestation, which healed without visible scars. Immunohistochemical analysis of wound sites was performed to assess reinnervation, using antibodies to the pan neuronal marker PGP9.5 as well as to the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). Staining for the endothelial marker von Willebrand factor (VWF) allowed comparison of reinnervation and revascularisation. Wounds were harvested at timepoints from day1 after wounding to postnatal day6. Quantification of wound reinnervation and revascularisation was performed for timepoints up to 6days post-wounding. Hypervascularisation of the wounds occurred within 24h, and blood vessel density within the wounds remained significantly elevated until postnatal day2 (4days post- wounding), after which VWF immunoreactivity was similar between wound and control groups. Wound nerve density returned to a level similar to that of unwounded skin within 48h of wounding, and PGP9.5 immunoreactive nerve fibre density remained similar to control skin thereafter. CGRP and SP immunoreactivity followed a similar pattern to that of PGP9.5, although wound levels did not return to those of control skin until postnatal day1. Scarless fetal wounds appeared to regenerate their nerve and blood vessel microanatomy perfectly after a period of hypervascularisation. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

Henderson J.,Addenbrookes Hospital | Ferguson M.W.J.,Renovo Ltd | Terenghi G.,University of Manchester
Wound Repair and Regeneration | Year: 2011

Denervated wounds fail to heal normally, and hypertrophic scars are abnormally innervated. Wounds can be manipulated with cytokines to reduce subsequent scarring. Wounds treated with the antiscarring cytokine interleukin 10 (IL10) were investigated to assess if the treatment alterered patterns of reinnervation and revascularization as the wounds matured into scars. Thirty CD1 mice underwent intradermal injection of 100 μL phosphate-buffered saline (PBS) containing 125 ng IL10 or placebo at the margins of 1 cm2 full thickness dorsal skin excisions at the time of wounding and at 24 hours after wounding. Wounds were not dressed. Six IL10-treated and six control were harvested days 7, 14, 21, 42 and 84 postoperatively. Sections underwent histological scar assessment along with immunohistochemical staining for protein gene product 9.5 (PGP9.5), a pan-neuronal marker, and the sensory neuropeptides calcitonin gene related peptide (CGRP) and substance P (SP). The endothelial marker von Willebrand factor (VWF) was used to allow co-localization and quantification of blood vessels. Quantitative analysis was performed on the periphery and center of wounds. Wounds treated with IL10 healed with dermal collagen organized into a pattern more closely resembling normal skin than control wounds. IL10 changed the pattern of CGRP reinnervation during the healing process, but at 84 days, the density levels of all nerve fiber types were similar to controls. Wounds treated with IL10 were more vascular than untreated wounds during healing, but by 84 days, VWF density was that of unwounded skin. © 2011 by the Wound Healing Society.

Renovo Corporation | Date: 2013-01-15


RENOVO Ltd | Date: 2011-10-07

The present invention relates to the use of a peptide, or derivative thereof of general formula X1-X2-X3-ThT-X4-LyS-X5-ATg-X6 for promoting accelerated wound healing with reduced scarring. X1 is Ala or Gly; X2 is Tyr or Phe; X3, X4 and X5 are independently selected from the group comprising Met, He, Leu and Val; and X6 is selected from the group comprising Asp, Gln and Glu.

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