title: Cultured Human Epidermis Combined With Meshed Skin Autografts Accelerates Epithelialization and Granulation Tissue Formation in a Rat Model.
abstract: BACKGROUND
  As the take rate of cultured epidermal autografts in burn wound treatment is variable, widely expanded meshed auto skin grafts are often used in combination with cultured epidermal autograft to increase the take rate and achieve definitive wound coverage. However, a long time (3-4 weeks) required to prepare a cultured epidermis sheet is a disadvantage. Allogeneic cultured epidermis can be prepared in advance and cryopreserved to be used in combination with auto meshed skin grafts for treating third-degree burns. Nevertheless, the human cultured epidermis (hCE) has not been proved to accelerate wound healing after meshed skin grafting. Here, we investigated the effect of hCE on wound healing in a rat model of meshed skin grafting.
  
  
  METHODS
  Human cultured epidermis was prepared from human neonatal foreskin and assessed by the release of growth factors into the culture medium using enzyme-linked immunosorbent assay. Skin wounds were inflicted on male F344 rats and treated by the application of widely meshed (6:1 ratio) autogenous skin grafts with or without hCE (n = 8 rats per group). Wound area, neoepithelium length, granulation tissue formation, and neovascularization were evaluated on day 7 postgrafting.
  
  
  RESULTS
  Human cultured epidermis secreted IL-1α, Basic fibroblast growth factor, platelet-derived growth factor-AA, TGF-α, TGF-β1, and vascular endothelial growth factor in vitro. In rats, hCE accelerated wound closure (P = 0.003), neoepithelium growth (P = 0.019), and granulation tissue formation (P = 0.043), and increased the number of capillaries (P = 0.0003) and gross neovascularization area (P = 0.008) compared with the control group.
  
  
  CONCLUSIONS
  The application of hCE with meshed grafts promoted wound closure, possibly via secretion of growth factors critical for cell proliferation and migration, suggesting that hCE can enhance the healing effect of widely expanded skin autografts.
authors.affiliation: From the *Department of Plastic and Reconstructive Surgery, Kyoto University Graduate School of Medicine, Syogoin Sakyo-ku, Kyoto; †Department of Plastic and Reconstructive Surgery, Kansai Medical University, Hirakata, Osaka; and ‡Japan Tissue Engineering, Co., Ltd., Miyakitadori, Gamagori, Aichi, Japan.
authors.forename: Michiharu
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Morimoto
authors.forename: Masukazu
authors.initials: M
authors.lastname: Inoie
authors.forename: Miki
authors.initials: M
authors.lastname: Takahagi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ogino
authors.forename: Chizuru
authors.initials: C
authors.lastname: Jinno
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D064592:Autografts; D002056:Burns / Q000601:surgery*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000078404:Epidermal Cells; D006097:Granulation Tissue / Q000166:cytology*; D006801:Humans; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D062326:Re-Epithelialization / Q000502:physiology*; D016038:Skin Transplantation / Q000379:methods*; D014945:Wound Healing / Q000502:physiology