Photodynamic modulation of wound healing with BPD-MA and CASP.

Abstract

Wound healing is an intricate process requiring the orchestration of cells, growth factors, cytokines, and the extracellular matrix. Cytokines, specifically TGF-beta, are believed to be instrumental in sustaining the fibrotic process, which leads to scarring. Photodynamic therapy (PDT) uses potent photosensitizers, which induce a wide range of effects on cells and the extracellular matrix. The influences of PDT on wound healing are not well known. Seven full-thickness incisional wounds were placed on each of 24 hairless Sprague Dawly rats, three wounds on one flank serving as dark controls and four on the contralateral side treated with PDT. Wounds were created two days before, one hour before, or one hour after red light exposure with an argon ion pumped dye laser. Twelve rats were injected with 0.25 mg/kg or 0.5 mg/kg of the PDT drug, BPD-MA, and the other 12 with 5 mg/kg or 10 mg/kg of the PDT drug, CASP, 3 and 24 hours prior to irradiation of light, respectively. At low doses of both photosensitizers, animals were irradiated with 1, 5, 10, and 20 J/cm2. At higher doses of BPD-MA and CASP animals were treated with 10, 20, 50, and 100 J/cm2 of light. Wounds were examined each day for 14 days and noted for edema, erythema, inflammation, necrosis, and quality of scarring. Wounds were also photographed at day 0, 2, 5, 8, and 14 post-irradiation. All animals were sacrificed 14 days after irradiation and the wounds were evaluated by light microscopy. Grossly, animals treated with 0.25 mg/kg BPD-MA showed no effect with PDT. Animals treated with 0.5 mg/kg BPD, and 5 and 10 mg/kg CASP showed responses that varied with both light and drug dose. Erythema, edema, inflammation, and necrosis attributed to PDT were all observed, but there was no apparent influence of PDT on either the rate or final appearance of wound healing. Histologically, there were no apparent differences between treated and untreated sites, regardless of the drug, dose of light, or time of irradiation. A single PDT treatment given before or after skin wounds does not apparently alter wound healing even when PDT caused brisk inflammatory reactions. PDT may have effects that were not detected. We conclude that PDT does not greatly influence incisional skin wound healing in the rat model.