title: Gelatin-based hydrogel for vascular endothelial growth factor release in peripheral nerve tissue engineering.
abstract: Hydrogels are promising materials in regenerative medicine applications, due to their hydrophilicity, biocompatibility and capacity to release drugs and growth factors in a controlled manner. In this study, biocompatible and biodegradable hydrogels based on blends of natural polymers were used in in vitro and ex vivo experiments as a tool for VEGF-controlled release to accelerate the nerve regeneration process. Among different candidates, the angiogenic factor VEGF was selected, since angiogenesis has been long recognized as an important and necessary step during tissue repair. Recent studies have pointed out that VEGF has a beneficial effect on motor neuron survival and Schwann cell vitality and proliferation. Moreover, VEGF administration can sustain and enhance the growth of regenerating peripheral nerve fibres. The hydrogel preparation process was optimized to allow functional incorporation of VEGF, while preventing its degradation and denaturation. VEGF release was quantified through ELISA assay, whereas released VEGF bioactivity was validated in human umbilical vein endothelial cells (HUVECs) and in a Schwann cell line (RT4-D6P2T) by assessing VEGFR-2 and downstream effectors Akt and Erk1/2 phosphorylation. Moreover, dorsal root ganglia explants cultured on VEGF-releasing hydrogels displayed increased neurite outgrowth, providing confirmation that released VEGF maintained its effect, as also confirmed in a tubulogenesis assay. In conclusion, a gelatin-based hydrogel system for bioactive VEGF delivery was developed and characterized for its applicability in neural tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Italy.|Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), University of Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Gnavi
authors.affiliation: Institute for Cancer Research and Treatment at Candiolo (IRCC), Torino, Italy.|Department of Oncology, University of Torino, Italy.
authors.forename: L
authors.initials: L
authors.lastname: di Blasio
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tonda-Turo
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Italy.|Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), University of Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mancardi
authors.affiliation: Institute for Cancer Research and Treatment at Candiolo (IRCC), Torino, Italy.|Department of Oncology, University of Torino, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Primo
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ciardelli
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gambarotta
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Italy.|Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), University of Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Geuna
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Perroteau
mesh_terms: D043925:Angiogenesis Inducing Agents; D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D005780:Gelatin / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D018919:Neovascularization, Physiologic; D009416:Nerve Regeneration / Q000502:physiology; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D020100:Hydrogels; D042461:Vascular Endothelial Growth Factor A; D005780:Gelatin
keywords: drug-releasing hydrogel; gelatin hydrogels; nerve regeneration; peripheral nerve; tissue engineering; vascular endothelial growth factor