The influence of a PHI-5-loaded silicone membrane, on cutaneous wound healing in vivo

Abstract

This study investigated whether a novel ionogenic substance, containing amongst others zinc and rubidium (PHI-5; Dermagenics Inc, Memphis, TN, USA), could improve the healing of full-thickness skin wounds. Uniform wounds were created on the right flank of guinea pigs. Micro-grooved silicone rubber membranes, containing 0 (controls), 1.25, 5.00, or 10.00 microg PHI-5, were sutured onto this wound. Standardized digital wound photographs were made after 1, 3, and 6 weeks. Also, wound biopsies were taken after 3 and 6 weeks for histological and histomorphometrical evaluation. For all study groups, 6 animals were used. Analysis of the 1-week digital photographs showed that the surface area of the wounds decreased significantly, with an increasing PHI-5 concentration. No other differences were found in the wound photographs. Also, no differences were measured in histomorphometry at 3 and 6 weeks. Concluding, in our study model a single application of PHI-5 did have a significant positive influence on initial wound healing.

Fig. 1

Surgical procedure. (A) The surgical area was drawn onto the skin using a pre-fabricated steel mold. (B) Anaesthetized guinea pig with drawing on right flank. (C) Circular wound, 2 cm Ø, after application of the silicone membrane. (D) Application of bandage

Fig. 2

Morphometrical analysis of a wound at day 7 (A) Wound, with calibration ruler. (B) Wound Surface Area (WSA). (C) Reference Surface Area (RSA)

Fig. 3

Histomorphometrical measurements on a histological section, 3 weeks after surgery. A = length of neo-epithelium B = wound opening, C = width of granulation tissue ED = epidermis, HF = hair follicle, CT = connective tissue, GT = granulation tissue, PC = panniculus carnosus, PA = panniculus adiposus

Fig. 4

Histomorphometrical measurements on a histological section, 6 weeks after surgery. Length of superficial granulation tissue is measured at three levels (A, B, C), as well as the narrowest distance between hair follicles (D)

Fig. 5

Wound appearance. (A) Day 7, all wounds are still open. (B, C) Day 21, wounds are either (B) nearly or (C) fully closed. (D) Day 42, all wounds are closed, producing a linear craniocaudal scar

Fig. 6

Mean Wound Surface Area (WSA). Note that on day 7, with an increasing concentration of PHI-5, the wound surface was significantly smaller. Bars indicate SD

Fig. 7

Mean Reference Surface Area (RSA). In all groups, the RSA significantly expands over the days. Note also the trend of a smaller RSA with an increasing concentration of PHI-5 on day 7. These differences resemble those of the WSA, although here are not significant. Bars indicate SD

Fig. 8

Histological section, HE staining, 3 weeks after surgery. (A) A large epithelial defect is still present. (B) Higher magnification, note that the basal cell layer is deficient over the woundbed area

Fig. 9

Histological section, HE staining, 3 weeks after surgery. (A) The whole surgical wound area is covered by a new layer of epithelium (B) Higher magnification, note that the new epithelial layer contains an intact layer of basal cells

Fig. 10

Histological sections, HE staining, 6 weeks after surgery. (A) and (B) All sections are fully covered with epithelium, but contain varying amounts of granulation tissue