title: Tissue-Engineered Skin Substitute Enhances Wound Healing after Radiation Therapy.
abstract: OBJECTIVE
  When given in conjunction with surgery for treating cancer, radiation therapy may result in impaired wound healing, which, in turn, could cause skin ulcers. In this study, bilayer and monolayer autologous skin substitutes were used to treat an irradiated wound.
  
  
  METHODS
  A single dose of 30 Gy of linear electron beam radiation was applied to the hind limb of nude mice before creating the skin lesion (area of 78.6 mm). Monolayer tissue-engineered skin substitutes (MTESSs) were prepared by entrapping cultured keratinocytes in fibrin matrix, and bilayer tissue-engineered skin substitutes (BTESSs) were prepared by entrapping keratinocytes and fibroblasts in separate layers. Bilayer tissue-engineered skin substitute and MTESS were implanted to the wound area. Gross appearance and wound area were analyzed to evaluate wound healing efficiency. Skin regeneration and morphological appearance were observed via histological and electron microscopy. Protein expressions of transforming growth factor β1 (TGF-β1), platelet-derived growth factor BB (PDGF-BB), and vascular endothelial growth factor (VEGF) in skin regeneration were evaluated by immunohistochemistry (IHC).
  
  
  RESULTS
  Macroscopic observation revealed that at day 13, treatments with BTESS completely healed the irradiated wound, whereas wound sizes of 1.1 ± 0.05 and 6.8 ± 0.14 mm were measured in the MTESS-treated and untreated control groups, respectively. Hematoxylin-eosin (H&E) analysis showed formation of compact and organized epidermal and dermal layers in the BTESS-treated group, as compared with MTESS-treated and untreated control groups. Ultrastructural analysis indicates maturation of skin in BTESS-treated wound evidenced by formation of intermediate filament bundles in the dermal layer and low intercellular space in the epidermal layer. Expressions of TGF-β1, PDGF-BB, and VEGF were also higher in BTESS-treated wounds, compared with MTESS-treated wounds.
  
  
  CONCLUSIONS
  These results indicate that BTESS is the preferred treatment for irradiated wound ulcers.
authors: Mohd Fauzi bin Mh Busra, BSc, is a PhD candidate at the Tissue Engineering Centre of the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) in Kuala Lumpur, Malaysia. Shiplu Roy Chowdhury, PhD, is a Research Fellow at the Tissue Engineering Centre of the UKMMC. Fuad bin Ismail, MD, is the Head of the Department of Radiotherapy and Oncology at the UKMMC. Aminuddin bin Saim, MD, is an Ear, Nose, and Throat Specialist at the Ear, Nose, and Throat Consultant Clinic, at the Ampang Puteri Specialist Hospital in Selangor, Malaysia, as well as a Consultant at the Tissue Engineering Centre of the UKMMC. Ruszymah Bt Hj Idrus, MD, PhD, is a Professor in the Department of Physiology at UKMMC.
authors: Mohd Fauzi bin Mh
authors: MF
authors: Busra
authors: Shiplu Roy
authors: SR
authors: Chowdhury
authors: Fuad
authors: F
authors: bin Ismail
authors: Aminuddin
authors: A
authors: bin Saim
authors: Ruszymah Bt Hj
authors: RB
authors: Idrus
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D017690:Cell Transplantation / Q000379:methods; D051379:Mice; D011878:Radiotherapy / Q000009:adverse effects*; D016038:Skin Transplantation; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*; D014945:Wound Healing / Q000502:physiology* / Q000528:radiation effects