title: Suitability of the rat subdermal model for tissue engineering of heart valves.
abstract: BACKGROUND
  Tissue engineering (TE) is a promising approach to overcome problems associated with biological heart valve prosthesis. Currently several animal models are used to advance this method. The rat subdermal model is uncomplicated and widely used, but its suitability for TE has not yet been shown.
  
  
  METHODS
  Using the rat subdermal model we implanted two decellularized porcine aortic wall specimens (of which one was endothelialized) and one native porcine aortic wall specimen in 30 Lewis rats, respectively. Endothelial cells (EC) were harvested from the rat jugular veins. After explantation Hematoxylin/Eosin-staining, CD-68-positive cell staining, fibroblast-staining and Von-Willebrand factor staining were performed.
  
  
  RESULTS
  All animals survived without complications. Endothelialization was confirmed to be effective by Giemsa staining. Histological evaluation of specimens in Hematoxylin/Eosin staining showed significant decrease (p<0.05) of inflammatory reaction (confirmed by CD-68-positive cell staining) after decellularization. All specimens showed strongest inflammatory reactions at areas of destroyed extracellular matrix. Fibroblasts could be detected in all specimens, with strongest infiltration in decellularized specimens (p<0.05). Surrounding endothelialized specimens had no monolayer of endothelial cells, but a higher density of blood vessels occurred (p<0.05).
  
  
  CONCLUSIONS
  The subdermal model provides excellent contact of host tissue with implanted specimens leading to rapid cellular infiltration; therefore, we could ascertain reduced inflammatory response to decellularized tissue. Due to the subdermal position, an absence of blood stream and mechanical stress occurs, which influences cellular repopulation; therefore, endothelialization did not lead to an EC monolayer, but rather to increased vascularization. Thus, the model appears ideal for investigating basic biological compatibility, but further questions must be researched using other models.
authors.affiliation: Department of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Christ
authors.affiliation: Department of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Dohmen
authors.affiliation: Department of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Holinski
authors.affiliation: Department of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schönau
authors.affiliation: Department of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Heinze
authors.affiliation: Department of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Konertz
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D001808:Blood Vessels / Q000166:cytology; D020405:Dermis / Q000502:physiology*; D042783:Endothelial Cells; D005347:Fibroblasts / Q000166:cytology; D006351:Heart Valves / Q000502:physiology*; D023421:Models, Animal; D009000:Monocytes / Q000166:cytology; D011917:Rats, Inbred Lew; D013194:Staining and Labeling; D034421:Sus scrofa; D023822:Tissue Engineering / Q000379:methods*