title: Early kinetics of integration of collagen-glycosaminoglycan regenerative scaffolds in a diabetic mouse model.
abstract: BACKGROUND
  Collagen-glycosaminoglycan scaffolds, originally designed to treat severe burns, are now commonly used in patients with complex wounds associated with diabetes mellitus. In this study, the authors investigated how the thickness of the scaffold would affect cellular integration with the diabetic host and whether this can be accelerated using subatmospheric pressure wound therapy devices.
  
  
  METHODS
  Collagen-glycosaminoglycan scaffolds, 500 to 2000-μm thick, were applied to dorsal wounds in genetically diabetic mice. In addition, 1000-μm collagen-glycosaminoglycan scaffolds with and without silicone were treated with a subatmospheric pressure device (-125 mmHg). On days 5 and 10, cellular and vascular integration of tissues was studied by histology, immunohistochemistry, corrosion casting, and qRT-polymerase chain reaction.
  
  
  RESULTS
  Cells and vessels from the wound surface populated the scaffold to form layers with varying cellular density. Areas of high cell density and proliferation were noted at the bottom of the scaffold. Increasing the thickness of the scaffold did not affect the extent of cellular ingrowth, so that thicker scaffolds had a thicker residual acellular layer on the surface. The thickness of cellular ingrowth was stable between days 5 and 10, whereas vessels seen in the scaffolds on day 10 were not yet present on day 5. Subatmospheric pressure devices applied to silicone-covered collagen-glycosaminoglycan scaffolds minimized the granulation tissue formation beneath the scaffold, which enhanced vessel ingrowth.
  
  
  CONCLUSIONS
  The early kinetics of cellular integration into collagen-glycosaminoglycan scaffolds is independent of scaffold thickness in a diabetic wound model. Scaffold adherence to the wound and integration can be improved using a subatmospheric pressure device.
authors.affiliation: Boston, Mass.; Magdeburg and Mainz, Germany; Padova, Italy; and Vienna, Austria From the Tissue Engineering and Wound Healing Laboratory, Division of Plastic Surgery, Brigham & Women's Hospital and Harvard Medical School; the Department of Plastic, Aesthetic, and Hand Surgery, University of Magdeburg; the Institute of Plastic Reconstructive and Aesthetic Surgery, University of Padova; the Clinical Institute of Pathology, University of Vienna; and the Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg University of Mainz.
authors.forename: Yvonne I
authors.initials: YI
authors.lastname: Heit
authors.forename: Luca
authors.initials: L
authors.lastname: Lancerotto
authors.forename: Raul
authors.initials: R
authors.lastname: Cortes
authors.forename: Ildiko
authors.initials: I
authors.lastname: Mesteri
authors.forename: Maximilian
authors.initials: M
authors.lastname: Ackermann
authors.forename: Rachel
authors.initials: R
authors.lastname: Hollander
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Douaiher
authors.forename: Moritz A
authors.initials: MA
authors.lastname: Konerding
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
mesh_terms: D000818:Animals; D003094:Collagen / Q000502:physiology*; D048909:Diabetes Complications; D006025:Glycosaminoglycans / Q000502:physiology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012038:Regeneration / Q000502:physiology; D012867:Skin; D054457:Tissue Scaffolds; D014947:Wounds and Injuries / Q000503:physiopathology / Q000601:surgery*
chemical_list: D006025:Glycosaminoglycans; D003094:Collagen