title: Tissue integration of collagen-based matrices: an experimental study in mice.
abstract: OBJECTIVE
  To test whether or not tissue integration, biodegradation, and new blood vessel formation in two collagen-based matrices depend on the level of chemical cross-linking.
  
  
  METHODS
  Two collagen matrices with high (CM1) and low (CM2) levels of chemical cross-linking were randomly implanted in two pouches in 14 athymic nude mice. Three and 6 weeks later, the animals were euthanized. Histologic and histomorphometric measurements were performed on paraffin-embedded sections.
  
  
  RESULTS
  Both collagen matrices integrated well into the surrounding soft tissues. The level of cross-linking and duration of implantation had an effect on the formation of new blood vessels. More blood vessels (n = in absolute numbers) were found in outer compartments compared to the central compartments of the matrices, reaching 5.6 (CM2) vs. 4.3 (CM1) at 3 weeks, and 5.3 (CM2) vs. 7.3 (CM1) at 6 weeks. Similarly, connective tissue formation increased for both matrices between 3 and 6 weeks, whereas the amount of remaining collagen network gradually decreased over time being more pronounced for CM1 (-50%) compared to CM2 (-15%).
  
  
  CONCLUSIONS
  The degree of cross-linking was negatively correlated for all outcome measures resulting in improved tissue integration, superior matrix stability and enhanced angiogenic patterns for the less cross-linked collagen matrix (CM2) in this experimental study in mice.
authors.affiliation: Clinic of Fixed and Removable Prosthodontics and Dental Material Science, Center of Dental Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Thoma
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Villar
authors.forename: David L
authors.initials: DL
authors.lastname: Cochran
authors.forename: Christoph H F
authors.initials: CH
authors.lastname: Hämmerle
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Jung
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D005260:Female; D008567:Membranes, Artificial; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D008567:Membranes, Artificial; D003094:Collagen