Topical photodynamic therapy following excisional wounding of human skin increases production of transforming growth factor-β3 and matrix metalloproteinases 1 and 9, with associated improvement in dermal matrix organization

Br J Dermatol. 2014 Jul;171(1):55-62. doi: 10.1111/bjd.12843. Epub 2014 Jun 24.

Abstract

Background: Animal studies report photodynamic therapy (PDT) to improve healing of excisional wounds; the mechanism is uncertain and equivalent human studies are lacking.

Objectives: To explore the impact of methyl aminolaevulinate (MAL)-PDT on clinical and microscopic parameters of human cutaneous excisional wound healing, examining potential modulation through production of transforming growth factor (TGF)-β isoforms.

Methods: In 27 healthy older men (60-77 years), a 4-mm punch biopsy wound was created in skin of the upper inner arm and treated with MAL-PDT three times over 5 days. An identical control wound to the contralateral arm was untreated and both wounds left to heal by secondary intention. Wounds were re-excised during the inflammatory phase (7 days, n = 10), matrix remodelling (3 weeks, n = 8) and cosmetic outcome/dermal structure (9 months, n = 9). Production of TGF-β1, TGF-β3 and matrix metalloproteinases (MMPs) was assessed by immunohistochemistry alongside microscopic measurement of wound size/area and clinical assessment of wound appearance.

Results: MAL-PDT delayed re-epithelialization at 7 days, associated with increased inflammation. However, 3 weeks postwounding, treated wounds were smaller with higher production of MMP-1 (P = 0·01), MMP-9 (P = 0·04) and TGF-β3 (P = 0·03). TGF-β1 was lower than control at 7 days and higher at 3 weeks (both P = 0·03). At 9 months, MAL-PDT-treated wounds showed greater, more ordered deposition of collagen I, collagen III and elastin (all P < 0·05).

Conclusions: MAL-PDT increases MMP-1, MMP-9 and TGF-β3 production during matrix remodelling, ultimately producing scars with improved dermal matrix architecture.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Aged
  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / analogs & derivatives*
  • Arm
  • Healthy Volunteers
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Photochemotherapy / methods
  • Photosensitizing Agents / administration & dosage*
  • Re-Epithelialization / drug effects
  • Skin / injuries*
  • Transforming Growth Factor beta3 / biosynthesis*
  • Wound Healing / drug effects

Substances

  • Photosensitizing Agents
  • Transforming Growth Factor beta3
  • methyl 5-aminolevulinate
  • Aminolevulinic Acid
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1