title: Effects of VEGF loading on scaffold-confined vascularization.
abstract: Adequate vascularization of tissue-engineered constructs remains a major challenge in bone grafting. In view of this, we loaded ß-tricalcium-phosphate (ß-TCP) and porous poly(L-lactide-co-glycolide) (PLGA) scaffolds via collagen coating with vascular endothelial growth factor (VEGF) and studied whether the VEGF loading improves scaffold angiogenesis and vascularization. Dorsal skinfold chambers were implanted into 48 balb/c mice, which were assigned to 6 groups (n = 8 each). Uncoated (controls), collagen-coated, and additionally VEGF-loaded PLGA and ß-TCP scaffolds were inserted into the chambers. Angiogenesis, neovascularization, and leukocyte-endothelial cell interaction were analyzed repeatedly during a 14-day observation period using intravital fluorescence microscopy. Furthermore, VEGF release from PLGA und ß-TCP scaffolds was studied by ELISA. Micromorphology was studied from histological specimens. Unloaded ß-TCP scaffolds showed an accelerated and increased angiogenic response when compared with unloaded PLGA scaffolds. In vitro, PLGA released significantly higher amounts of VEGF compared with ß-TCP at the first two days resulting in a rapid drop of the released amount at the following days up to day 7 where the VEGF release was negligible. Nonetheless, in vivo VEGF loading increased neovascularization, especially in ß-TCP scaffolds. This increased vascularization was associated with a temporary leukocytic response with pronounced leukocyte-endothelial cell interaction at days 3 and 6. Histology revealed adequate host tissue response and engraftment of both ß-TCP and PLGA scaffolds. Our study demonstrates that ß-TCP scaffolds offer more suitable conditions for vascularization than PLGA scaffolds, in particular if they are loaded with VEGF.
authors: Department of Oral and Maxillofacial Surgery, Hannover Medical School, Hannover, Germany.
authors: Daniel
authors: D
authors: Lindhorst
authors: Frank
authors: F
authors: Tavassol
authors: Constantin
authors: C
authors: von See
authors: Paul
authors: P
authors: Schumann
authors: Matthias W
authors: MW
authors: Laschke
authors: Yves
authors: Y
authors: Harder
authors: Kai-Hendrik
authors: KH
authors: Bormann
authors: Harald
authors: H
authors: Essig
authors: Horst
authors: H
authors: Kokemüller
authors: Andreas
authors: A
authors: Kampmann
authors: André
authors: A
authors: Voss
authors: Rolf
authors: R
authors: Mülhaupt
authors: Michael D
authors: MD
authors: Menger
authors: Nils-Claudius
authors: NC
authors: Gellrich
authors: Martin
authors: M
authors: Rücker
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism; D006439:Hemodynamics; D020007:Implants, Experimental; D007249:Inflammation; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D042461:Vascular Endothelial Growth Factor A; C485817:beta-tricalcium phosphate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid