title: Experimental ASD closure using autologous cell-seeded interventional closure devices.
abstract: OBJECTIVE
  Atrial septal defect (ASD) occluders are permanent implants in paediatric cardiology which serve as mechanical shields until complete overgrowth and incorporation of the occluding device by autologous tissue has occurred. Thereafter, the foreign body material making up the device is dispensable and bears potential long-term adverse effects. Rapid, firm and complete incorporation into the atrial septal wall should be a prerequisite for biodegradable devices. In this study, the feasibility of using autologous cell-seeded devices was investigated by (a) testing the influence of a collagen coating on cellular stress resistance in vitro and (b) comparing the short-term effects between cell-seeded, collagen-coated and acellular ASD occluders in vivo.
  
  
  METHODS
  Native and collagen-coated Dacon fabrics and Starflex-devices were pre-seeded with autologous fibroblasts (skin biopsy) and evaluated using various mechanical stress tests. In a sheep model interventionally created ASDs were closed using either autologous pre-seeded or conventional (acellular) Starflex-devices.
  
  
  RESULTS
  ASD closure devices were successfully pre-seeded with autologous cells. The incubation period needed, the cellular density achieved and the mechanical stability of the cytolayer after mechanical stressing (implantation) were improved by applying a collagen matrix on the fabric. Compared to the thin layer of ingrown tissue seen on conventional occluders after 30 days in vivo, a thicker layer of organising, newly formed granulation tissue on pre-seeded collagen-coated devices embedded not only the Dacron fabric, but also completely covered the spring arms of the device underneath a layer of neo-endothelium.
  
  
  CONCLUSIONS
  Autologous cell pre-seeding of interventional closure devices is feasible since the cells survive the mechanical stress encountered during implantation. Rapid, firm and complete ingrowth of occluder devices into a thicker layer of young fibrous granulation tissue can be achieved, but an increased thrombogenicity currently limits the in vivo application.
authors.affiliation: Department of Paediatric Cardiology and Paediatric Intensive Care Medicine, Hannover Medical School, Carl Neuberg Strasse 1, D-30627 Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jux
authors.forename: Harald
authors.initials: H
authors.lastname: Bertram
authors.forename: Peter
authors.initials: P
authors.lastname: Wohlsein
authors.forename: Michael
authors.initials: M
authors.lastname: Brügmann
authors.forename: Petra
authors.initials: P
authors.lastname: Wüboldt
authors.forename: Christoph
authors.initials: C
authors.lastname: Fink
authors.forename: Thomas
authors.initials: T
authors.lastname: Paul
authors.forename: Gerd
authors.initials: G
authors.lastname: Hausdorf
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002404:Catheterization; D002455:Cell Division; D002470:Cell Survival; D003094:Collagen; D005347:Fibroblasts; D006344:Heart Septal Defects, Atrial / Q000628:therapy*; D015603:Keratinocytes; D023421:Models, Animal; D012756:Sheep; D013314:Stress, Mechanical
chemical_list: D003094:Collagen