Effects of VEGF loading on scaffold-confined vascularization.
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.
Lindhorst
Daniel
D
Department of Oral and Maxillofacial Surgery, Hannover Medical School, Hannover, Germany.
Tavassol
Frank
F
von See
Constantin
C
Schumann
Paul
P
Laschke
Matthias W
MW
Harder
Yves
Y
Bormann
Kai-Hendrik
KH
Essig
Harald
H
Kokemüller
Horst
H
Kampmann
Andreas
A
Voss
André
A
Mülhaupt
Rolf
R
Menger
Michael D
MD
Gellrich
Nils-Claudius
NC
Rücker
Martin
M
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*
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