CHANGE OF COLLAGEN IN NORMAL SKIN AND HEALING OF SURGICAL WOUND AFTER INTRADERMAL INJECTION OF BOTULINUM TOXIN A IN PORCINE

Abstract

This study was designed to study the effect BTX-A in the normal skin and healing process of full thickness wound after BTX-A intradermal injection in the pig model. In the 1st experiment, both sides of the dorsal region of pig were randomly injected with BTX-A as the treatment group and normal saline as the control group. In the 2nd experiment, round full-thickness wounds were performed at the skin on both sides of the dorsal region of pig and injected with BTX-A around the wound as the treatment group or normal saline as the control group. From the 1St experiment, the skins of both control and BTX-A groups showed inflammation and hemorrhage at the injection site. Severity of the lesions was decreased gradually until 72 hours post injection. For the histological evaluation, there was no difference of the amount of increased inflammatory cells, mainly macrophages and lymphocytes between the BTX-A and control groups. However, 21 days at post injection, in the BTX-A group of the increased inflammatory cells was significantly more than the control group. The increased of blood vessel in the BTX-A group was significantly more than the control group at day 3 and tended to be great at days 7, 14 and 21. For the mason trichrome staining, there was no significant difference of the intensity of positive blue color and arrangement of collagen between the control and BTX-A groups. Immunohistochemically, the number of Ki67 positive nuclei of fibroblasts of the BTX-A group was significantly more than the control group and the BTX-A groups on the 3rd day post-injection day but in reverse on the 21st post-injection days. The color intensity of collagen type I of the BTX-A group was greater than the control group on the 7th post-injection days. In the 2nd experiment, wound of the BTX-A and control groups had no significant difference of wound size at all time points. For the histological evaluation, the BTX-A groups had significantly less infiltration of inflammatory cells than the control group on the 3th and 14th post-operative day. The increased number of blood vessels of the control group was more than the BTX-A group on the 3rd post-operative day. For the mason trichrome staining, the intensity of positive blue color of collagen in the BTX-A group was significantly greater than the control group on the 21st post-operative days. The BTX-A group had more order arrangement of the collagen than the control group on the 14th and 21st post-operative days. In conclusion, the intradermal injection of the BTX-A is not harmful to the skin in pig model. Injection of BTX-A is advantageous in the early stages after injection. It could reduce inflammation and increases blood vessels, fibroblast proliferation and collagen type I synthesis. Moreover BTX-A could promote wound healing process by reducing inflammatory cells, increasing vessel proliferation and collagen, and inducing order arrangement of the collagen in the wound and adjacent area.