title: Vascular endothelial growth factor and fibroblast growth factor-2 incorporation in starch-based bone tissue-engineered constructs promote the in vivo expression of neovascularization mediators.
abstract: The ideal bone tissue-engineered (TE) construct remains to be found, although daily discoveries significantly contribute to improvements in the field and certainly have valuable long-term outcomes. In this work, different TE elements, aiming at bone TE applications, were assembled and its effect on the expression of several vascularization/angiogenesis mediators analyzed. Starch/polycaprolactone (SPCL) scaffolds, obtained by two different methodologies, were combined with fibrin sealant (Baxter(®)), human adipose-derived stem cells (hASCs), and growth factors (vascular endothelial growth factor [VEGF] or fibroblast growth factor-2 [FGF-2]), and implanted in vascular endothelial growth factor receptor-2 (VEGFR2)-luc transgenic mice. The expression of VEGFR2 along the implantation of the designed constructs was followed using a luminescence device (Xenogen(®)) and after 2 weeks, the explants were retrieved to perform histological analysis and reverse transcriptase-polymerase chain reaction for vascularization (VEGF and VEGFR1) and inflammatory (tumor necrosis factor-alpha, interleukin-4, and interferon-gamma) markers. It was showed that SPCL scaffolds obtained by wet spinning and by fiber bonding constitute an adequate support for hASCs. The assembled TE constructs composed by fibrin sealant, hASCs, VEGF, and FGF-2 induce only a mild inflammatory reaction after 2 weeks of implantation. Additionally, the release of VEGF and FGF-2 from the constructs enhanced the expression of VEGFR2 and other important mediators in neovascularization (VEGF and VEGFR1). These results indicate the potential of VEGF or FGF-2 within a bone TE construct composed by wet-spun SPCL, fibrin sealant, and hASCs in promoting the vascularization of newly formed tissue.
authors.affiliation: 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Taipas, Guimarães, Portugal.
authors.forename: Tírcia C
authors.initials: TC
authors.lastname: Santos
authors.forename: Tatjana J
authors.initials: TJ
authors.lastname: Morton
authors.forename: Martina
authors.initials: M
authors.lastname: Moritz
authors.forename: Sabine
authors.initials: S
authors.lastname: Pfeifer
authors.forename: Kathrin
authors.initials: K
authors.lastname: Reise
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Marques
authors.forename: António G
authors.initials: AG
authors.lastname: Castro
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
mesh_terms: D000328:Adult; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D058948:Cell Tracking; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D055806:Microvessels / Q000187:drug effects; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011091:Polyesters / Q000494:pharmacology; D013213:Starch / Q000494:pharmacology*; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D011091:Polyesters; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C016240:polycaprolactone; D013213:Starch; D040301:Vascular Endothelial Growth Factor Receptor-2