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Single‐stage application of a novel decellularized dermis for treatment‐resistant lower limb ulcers: Positive outcomes assessed by SIA scopy, laser perfusion, and 3 D imaging, with sequential timed histological analysis
Author(s) -
Greaves Nicholas S.,
Benatar Brian,
Baguneid Mohamed,
Bayat Ardeshir
Publication year - 2013
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12113
Subject(s) - medicine , wound healing , cd31 , perfusion , dermis , surgery , debridement (dental) , fibrosis , immunohistochemistry , decellularization , pathology , urology , biomedical engineering , tissue engineering
We present results of an original clinical study investigating efficacy of a decellularized dermal skin substitute ( DCD ) as part of a one‐stage therapeutic strategy for recalcitrant leg ulcers. Twenty patients with treatment‐resistant ulcers underwent hydrosurgical debridement, after which DCD was applied and covered with negative pressure dressings for 1 week. Participants were reviewed on seven occasions over 6 months. 3 D photography, full‐field laser perfusion imaging, spectrophotometric intracutaneous analysis, and sequential biopsies were used to monitor healing. Mean ulcer duration and surface area prior to DCD placement were 4.76 years (range 0.25–40 years) and 13.11 cm 2 (range 1.06–40.75 cm 2 ), respectively. Seventy percent of ulcers were venous. Surface area decreased in all patients after treatment (range 23–100%). Mean reduction was 87% after 6 months, and 60% of patients healed completely. Wound bed hemoglobin flux increased significantly 6 weeks after treatment ( p = 0.005). Histological and immunohistochemical analysis confirmed progressive DCD integration with colonization by host fibroblasts, lymphocytes, and neutrophils, resulting in fibroplasia, reepithelialisation, and angiogenesis, with correlating raised CD 31, collagen I , and collagen III levels. Subgroup analysis showed differing cellular behavior depending on wound duration, with delayed angiogenesis, reduced collagen deposition, and smaller reductions in surface area in ulcers present for over 1 year. The stain intensities of immunohistochemical markers including fibronectin, collagen, and CD 31 differed depending on depth from the wound surface and presence of intact epithelium. DCD safely produced significant improvement in treatment‐resistant leg ulcers. With no requirement for hospital admission, anesthetic, or autogenic skin grafting, this treatment could be administered in hospital and community settings.