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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
Author(s) -
Mills S.J.,
Farrar M.D.,
Ashcroft G.S.,
Griffiths C.E.M.,
Hardman M.J.,
Rhodes L.E.
Publication year - 2014
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.12843
Subject(s) - medicine , matrix metalloproteinase , wound healing , transforming growth factor , photodynamic therapy , biopsy , inflammation , elastin , skin biopsy , extracellular matrix , immunohistochemistry , pathology , surgery , chemistry , biochemistry , organic chemistry
Summary 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 ( MMP s) 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.