title: A composite fibrin-based scaffold for controlled delivery of bioactive pro-angiogenetic growth factors.
abstract: The aim of this study was to fabricate and characterize in vitro a novel composite scaffold that, combining good mechanical properties with a controlled and sustained release of bioactive pro-angiogenetic growth factors, should be useful for angiogenesis induction in organs/tissues in which is also necessary to give resistance and mechanical strength. Composite scaffolds, constituted by a synthetic biocompatible material, a poly(ether)urethane-polydimethylsiloxane blend, and a biological polymer, the fibrin, were manufactured by spray, phase-inversion technique. During the manufacturing process heparin and heparin-binding growth factors, such as VEGF(165) and bFGF, were incorporated into the fibrin layer. Microscopical examinations showed a homogeneous fibrin layer firmly adherent on top of the synthetic material. Tensile tests highlighted the high elasticity of the composite scaffold and its capability to maintain integrity up to high deformation. VEGF(165) and bFGF release were controlled by fibrinogen concentration, whereas it was not affected by heparin concentration, as revealed by ELISA assay. The biological activity of the released growth factors was maintained as demonstrated by HUVEC proliferation. Finally, scaffolds induced a low monocyte mRNA expression of inflammatory markers (IL-8, L-SEL, LFA-1 and iNOS). In conclusion, the new composite scaffolds, once implanted, providing a co-localization and temporal distribution of bioactive VEGF and bFGF in addition to good mechanical properties, may be useful to stimulate new vessels formation in ischemic tissues.
authors.affiliation: Laboratory for Biomaterials & Graft Technology, G. Pasquinucci Hospital, Institute of Clinical Physiology, CNR, 54100Massa, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Briganti
authors.forename: Dario
authors.initials: D
authors.lastname: Spiller
authors.forename: Chiara
authors.initials: C
authors.lastname: Mirtelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Kull
authors.forename: Claudio
authors.initials: C
authors.lastname: Counoupas
authors.forename: Paola
authors.initials: P
authors.lastname: Losi
authors.forename: Sonia
authors.initials: S
authors.lastname: Senesi
authors.forename: Rossella
authors.initials: R
authors.lastname: Di Stefano
authors.forename: Giorgio
authors.initials: G
authors.lastname: Soldani
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D055119:Elastic Modulus; D042783:Endothelial Cells / Q000187:drug effects; D005337:Fibrin / Q000737:chemistry*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008422:Materials Testing; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011140:Polyurethanes / Q000737:chemistry; D013499:Surface Properties; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D043925:Angiogenesis Inducing Agents; D003692:Delayed-Action Preparations; D004129:Dimethylpolysiloxanes; D011140:Polyurethanes; D042461:Vascular Endothelial Growth Factor A; C115016:polyetherurethane; D016222:Fibroblast Growth Factor 2; C013830:baysilon; D005337:Fibrin