title: Repair of surgically created diaphragmatic defect in rat with use of a crosslinked porous collagen scaffold.
abstract: Large defects in congenital diaphragmatic hernia are closed by patch repair, which is associated with a high complication risk and reherniation rate. New treatment modalities are warranted. We evaluated the feasibility of using an acellular biodegradable collagen bioscaffold for a regenerative medicine approach to close a surgically created diaphragmatic defect in a rat model. Scaffold degradation, cellular ingrowth and regeneration of the diaphragm were studied. In 25 rats, a subcostal incision was made and one third of the right hemidiaphragm was resected. Crosslinked porous type I collagen scaffolds (Ø ~ 14 mm) were sutured into the lesion. Rats were sacrificed at 2, 4, 8, 12 or 24 weeks after scaffold implantation. Implants were evaluated macroscopically and (immuno)histologically. Survival after surgery was 88% with no evidence of reherniation. Histological examination showed that the collagen scaffold degraded slowly and new collagen, elastin and mesothelium were deposited. Blood vessels were observed primarily at the outer borders of the scaffold; their number gradually increased in time. Muscle fibres were found on the scaffold covering up to 10% of the defect. Macroscopically, adhesion of the scaffold to the liver was observed. Use of a collagen scaffold to close a surgically created diaphragmatic defect is feasible, with evidence of new tissue formation. The use of crosslinked collagen scaffolds allows targeted modification; e.g. addition of growth factors to further stimulate growth of muscle cells.
authors.affiliation: Department of Biochemistry 280, NCMLS, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. K.Brouwer@ncmls.ru.nl
authors.forename: Katrien M
authors.initials: KM
authors.lastname: Brouwer
authors.forename: Willeke F
authors.initials: WF
authors.lastname: Daamen
authors.forename: Daphne
authors.initials: D
authors.lastname: Reijnen
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Verstegen
authors.forename: Gerwen
authors.initials: G
authors.lastname: Lammers
authors.forename: Theo G
authors.initials: TG
authors.lastname: Hafmans
authors.forename: Ronnie G
authors.initials: RG
authors.lastname: Wismans
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: René M
authors.initials: RM
authors.lastname: Wijnen
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D003964:Diaphragm / Q000293:injuries* / Q000473:pathology; D006548:Hernia, Diaphragmatic / Q000473:pathology / Q000628:therapy; D065630:Hernias, Diaphragmatic, Congenital; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D054457:Tissue Scaffolds
chemical_list: D003094:Collagen