title: Skin substitute-assisted repair shows reduced dermal fibrosis in acute human wounds validated simultaneously by histology and optical coherence tomography.
abstract: Skin substitutes are heterogeneous biomaterials designed to accelerate wound healing through provision of replacement extracellular matrix. Despite growing evidence for their use in chronic wounds, the role of skin substitutes in acute wound management and their influence on fibrogenesis remains unclear. Skin substitute characteristics including biocompatibility, porosity, and elasticity strongly influence cellular behavior during wound healing. Thus, we hypothesize that structural and biomechanical variation between biomaterials may induce differential scar formation after cutaneous injury. The following human prospective cohort study was designed to investigate this premise. Four 5-mm full thickness punch biopsies were harvested from 50 volunteers. In all cases, site 1 healed by secondary intention, site 2 was treated with collagen-GAG scaffold (CG), and decellularised dermis (DCD) was applied to site 3 while tissue extracted from site 4 was replaced (autograft). Healing tissue was assessed weekly with optical coherence tomography (OCT), before being excised on days 7, 14, 21, or 28 depending on study group allocation for later histological and immunohistochemical evaluation. Extracted RNA was used in microarray analysis and polymerase chain reaction of highlighted genes. Autograft treatment resulted in minimal fibrosis confirmed immunohistochemically and with OCT through significantly lower collagen I levels (p = 0.047 and 0.03) and reduced mean grayscale values (p = 0.038 and 0.015), respectively. DCD developed intermediate scar formation with partial rete ridge reformation and reduced fasiculonodular fibrosis. It was uniquely associated with late up-regulation of matrix metalloproteinases 1 and 3, oncostatin M, and interleukin-10 (p = 0.007, 0.04, 0.019, 0.019). Regenerated dermis was significantly thicker in DCD and autografts 28 days post-injury compared with control and CG samples (p = 0.003 and < 0.0001). In conclusion, variable fibrotic outcomes were observed in skin substitute-treated wounds with reduced scarring in autograft and DCD samples compared with controls. OCT enabled concurrent assessment of wound morphology and quantification of dermal fibrosis.
authors.affiliation: Plastic and Reconstructive Surgery Research, Institute of Inflammation and Repair, The University of Manchester.|Department of Vascular Surgery, University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital, Manchester.|Bioengineering Group, School of Materials, University of Manchester, andThe Pennine Acute Hospitals NHS Trust, The Royal Oldham Hospital, Oldham, United Kingdom.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Greaves
authors.affiliation: Plastic and Reconstructive Surgery Research, Institute of Inflammation and Repair, The University of Manchester.
authors.forename: Syed A
authors.initials: SA
authors.lastname: Iqbal
authors.affiliation: Plastic and Reconstructive Surgery Research, Institute of Inflammation and Repair, The University of Manchester.
authors.forename: Tom
authors.initials: T
authors.lastname: Hodgkinson
authors.affiliation: Department of Medical Statistics, University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital.
authors.forename: Julie
authors.initials: J
authors.lastname: Morris
authors.affiliation: Department of Histopathology, The Pennine Acute Hospitals NHS Trust, The Royal Oldham Hospital, Oldham, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: Benatar
authors.affiliation: Bioengineering Group, School of Materials, University of Manchester, andThe Pennine Acute Hospitals NHS Trust, The Royal Oldham Hospital, Oldham, United Kingdom.
authors.forename: Teresa
authors.initials: T
authors.lastname: Alonso-Rasgado
authors.affiliation: Department of Vascular Surgery, University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital, Manchester.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Baguneid
authors.affiliation: Plastic and Reconstructive Surgery Research, Institute of Inflammation and Repair, The University of Manchester.|Bioengineering Group, School of Materials, University of Manchester, andThe Pennine Acute Hospitals NHS Trust, The Royal Oldham Hospital, Oldham, United Kingdom.
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Bayat
mesh_terms: D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D002921:Cicatrix / Q000517:prevention & control; D005260:Female; D005355:Fibrosis / Q000473:pathology / Q000628:therapy; D005500:Follow-Up Studies; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012867:Skin / Q000293:injuries* / Q000473:pathology; D016038:Skin Transplantation / Q000379:methods*; D017768:Skin, Artificial; D013997:Time Factors; D041623:Tomography, Optical Coherence / Q000379:methods*; D014182:Transplantation, Autologous; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology / Q000601:surgery*; D055815:Young Adult