title: Decelerated vascularization in tissue-engineered constructs in association with diabetes mellitus in vivo.
abstract: OBJECTIVE
  Rapid blood vessel ingrowth in transplanted tissue engineering constructs is the key factor for successful incorporation, but many potential patients who may use engineered tissues suffer from widespread diseases that limit the capacity of neovascularization (e.g. diabetes). Thus, in vivo vascularization analyses of tissue-engineered constructs in angiogenically affected organisms are required.
  
  
  METHODS
  We therefore investigated the in vivo incorporation of collagen-coated and cell-seeded poly-L-lactide-co-glycolide scaffolds in diabetic B6.BKS(D)-Lepr(db)/J mice using repetitive intravital fluorescence microscopy over a time period of two weeks. For this purpose, scaffolds were seeded with osteoblast-like or bone marrow mesenchymal stem cells and implanted into the dorsal skinfold chambers of diabetic and non-diabetic (C57BL/6) mice.
  
  
  RESULTS
  Apart from slightly increased inflammatory parameters, diabetic mice showed significantly reduced capillary densities compared with non-diabetic animals from day 6 onward. In line with previous studies, more densely meshed microvascular networks were demonstrated in cell-seeded than in collagen-coated scaffolds from day 6 onward within the single groups (diabetic and control).
  
  
  CONCLUSIONS
  A large number of patients who suffer from systemic diseases that affect angiogenesis would profit from tissue engineering. Therefore, the challenge for the clinical introduction of tissue-engineered constructs will be to overcome the decreased angiogenesis in diabetic organisms.
authors.affiliation: Division of Cranio-Maxillo-Facial and Oral Surgery, University Hospital Zurich, Zurich, Switzerland. Electronic address: paulzueri@gmail.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Schumann
authors.affiliation: Division of Cranio-Maxillo-Facial and Oral Surgery, University Hospital Zurich, Zurich, Switzerland. Electronic address: Daniel.Lindhorst@usz.ch.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindhorst
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hannover Medical School, Hannover, Germany. Electronic address: Kampmann.Andreas@mh-hannover.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kampmann
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hannover Medical School, Hannover, Germany. Electronic address: Gellrich.Nils-Claudius@mh-hannover.de.
authors.forename: Nils-Claudius
authors.initials: NC
authors.lastname: Gellrich
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine, Hannover, Germany. Electronic address: sonja@krone-wolf.de.
authors.forename: Sonja
authors.initials: S
authors.lastname: Krone-Wolf
authors.affiliation: Clinic for Small Animal Surgery and Reproduction, Ludwig-Maximilians-University, Munich, Germany. Electronic address: ameylin@lmu.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.affiliation: Center of CAD/CAM and digital technologies in dentistry, Danube Private University, Krems-Stein, Austria. Electronic address: Constantin.See@DP-Uni.ac.at.
authors.forename: Constantin
authors.initials: C
authors.lastname: von See
authors.affiliation: Division of Cranio-Maxillo-Facial and Oral Surgery, University Hospital Zurich, Zurich, Switzerland. Electronic address: Thomas.Gander@usz.ch.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gander
authors.affiliation: Division of Cranio-Maxillo-Facial and Oral Surgery, University Hospital Zurich, Zurich, Switzerland. Electronic address: Martin.Lanzer@usz.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Lanzer
authors.affiliation: Division of Cranio-Maxillo-Facial and Oral Surgery, University Hospital Zurich, Zurich, Switzerland. Electronic address: Martin.Ruecker@usz.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Rücker
authors.affiliation: Division of Cranio-Maxillo-Facial and Oral Surgery, University Hospital Zurich, Zurich, Switzerland. Electronic address: Harald.Essig@usz.ch.
authors.forename: Harald
authors.initials: H
authors.lastname: Essig
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D011897:Random Allocation; D012016:Reference Values; D018570:Risk Assessment; D016038:Skin Transplantation / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D014945:Wound Healing / Q000502:physiology
keywords: Angiogenesis; B6.BKS(D)-Lepr(db)/J mouse; Intravital fluorescence microscopy; PLGA scaffold; Tissue engineering