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


OBJECTIVE
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.
Faculty of Life Sciences, University of Manchester, Manchester, U.K; Dermatology Centre, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Manchester, U.K.
S J
SJ
Mills
M D
MD
Farrar
G S
GS
Ashcroft
C E M
CE
Griffiths
M J
MJ
Hardman
L E
LE
Rhodes
D000279:Administration, Cutaneous; D000368:Aged; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001132:Arm; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D062326:Re-Epithelialization / Q000187:drug effects; D012867:Skin / Q000293:injuries*; D053782:Transforming Growth Factor beta3 / Q000096:biosynthesis*; D014945:Wound Healing / Q000187:drug effects
D017319:Photosensitizing Agents; D053782:Transforming Growth Factor beta3; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1