Photochemical Tissue Passivation (PTP) Prevents Contracture of Full Thickness Wounds
Rachel L. Goldstein, DO, Gem Runyan, BS, MS, Michael C. McCormack, MBA, Robert W. Redmond, PhD, Mark A. Randolph, MAS, William G. Austen, Jr., MD.
Massachusetts General Hospital, Boston, MA, USA.
PURPOSE: Large surface area wounds, resulting from burns, trauma, or iatrogenic injury, often result in significant scarring and wound contracture. Despite treatment with any of the currently available gold-standard therapies, contracture can still develop as a sequelae of the process of normal wound healing, specifically, myofibroblast activity. Photochemical Tissue Passivation (PTP) is a process that induces collagen cross-linking after a tissue is painted with photosensitizing dye and then exposed to visible light. PTP has also been shown to limit myofibroblast activity in healing surgical wounds. PTP is easy to perform and can be complete in minutes, and has been established as a safe treatment modality in animal and human studies. We hypothesize that PTP treatment to wounds can significantly decrease the morbidities associated with wound contracture by reinforcing the wound bed with collagen cross-linking and limiting the fibrotic response during wound healing.
METHODS: Full-thickness, excisional 1cm x 1cm wounds were created on the dorsum of C57BL/6 mice. Wounds were either left alone to heal as a control group, or were treated with PTP on the day the wounds were created. Wounds beds on animals in the treatment group received PTP treatment at a fluence of 60J/cm2. Wound areas were measured with serial photography for three weeks, at which time animals were euthanized and wound skin was harvested for histological processing with H&E and Masson's Trichrome staining. Histology was then reviewed by an expert dermatopathologist.
RESULTS: PTP visually prevented wound contracture throughout the study. Wound size on serial photography was calculated as a percentage of the original wound area. Sizes of PTP-treated wounds were almost three times greater than controls after one week (68.6±15% vs 25±9%, p=0.004) and almost seven times greater after two weeks (38.8±22% vs 5.6±6%, p=0.05). At the end of the three-week study, while control wounds had visually completely closed, PTP-treated wounds were not yet closed and were over 10 times larger than control wounds (19.3±20% vs 1.8±2%, p=0.17). On histologic review, PTP treatment promoted increased ingrowth and development of dermal cells, increased vascularity, and development of skin appendages compared to control wounds.
CONCLUSION: PTP prevents wound contracture in full-thickness, excisional wounds, and may accelerate the process of wound healing and development. These findings suggest future utility of PTP treatment not only for excisional wounds, but also for wounds with a high incidence of contracture and associated morbidity, including burns and skin-grafts.
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