A composite fibrin-based scaffold for controlled delivery of bioactive pro-angiogenetic growth factors.
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.
Briganti
Enrica
E
Laboratory for Biomaterials & Graft Technology, G. Pasquinucci Hospital, Institute of Clinical Physiology, CNR, 54100Massa, Italy.
Spiller
Dario
D
Mirtelli
Chiara
C
Kull
Silvia
S
Counoupas
Claudio
C
Losi
Paola
P
Senesi
Sonia
S
Di Stefano
Rossella
R
Soldani
Giorgio
G
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
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