The reinnervation pattern of wounds and scars after treatment with transforming growth factor β isoforms.

Abstract

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. 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). 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. 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.