title: Integration of scaffolds into full-thickness skin wounds: the connexin response.
abstract: Scaffolds have been reported to promote healing of hard-to-heal wounds such as burns and chronic ulcers. However, there has been little investigation into the cell biology of wound edge tissues in response to the scaffolds. Here, we assess the impact of collagen scaffolds on mouse full-thickness wound re-epithelialisation during the first 5 days of healing. We find that scaffolds impede wound re-epithelialisation, inducing a bulbous thickening of the wound edge epidermis as opposed to the thin tongue of migratory keratinocytes seen in normal wound healing. Scaffolds also increase the inflammatory response and the numbers of neutrophils in and around the wound. These effects were also produced by scaffolds made of alginate in the form of fibers and microspheres, but not as an alginate hydrogel. In addition, we find the gap junction protein connexin 43, which normally down-regulates at the wound edge during re-epithelialisation, to be up-regulated in the bulbous epidermal wound edge. Incorporation of connexin 43 antisense oligodeoxynucleotides into the scaffold can be performed to reduce inflammation whilst promoting scaffold biocompatibility.
authors: Department of Cell and Developmental Biology, University College London, Gower Street, WC1E 6BT, UK.
authors: Daniel J
authors: DJ
authors: Gilmartin
authors: Maia M
authors: MM
authors: Alexaline
authors: Chris
authors: C
authors: Thrasivoulou
authors: Anthony R J
authors: AR
authors: Phillips
authors: Suwan N
authors: SN
authors: Jayasinghe
authors: David L
authors: DL
authors: Becker
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008863:Microspheres; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry; D012867:Skin / Q000293:injuries / Q000473:pathology*; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000464:Alginates; D018031:Connexin 43; D006603:Hexuronic Acids; D020319:Oligodeoxyribonucleotides, Antisense; D011108:Polymers; D020723:Glucuronic Acid; D003094:Collagen
keywords: bioactivation; connexin 43; gap junctions; scaffolds; wound healing