Gelatin‐based hydrogel for vascular endothelial growth factor release in peripheral nerve tissue engineering

• Published in: Journal of tissue engineering and regenerative medicine Vol. 11; no. 2; pp. 459 - 470
• Main Authors: Gnavi, S, Blasio, L, Tonda‐Turo, C, Mancardi, A, Primo, L, Ciardelli, G, Gambarotta, G, Geuna, S, Perroteau, I
• Format: Journal Article
• Language: English
• Published: England Hindawi Limited 01.02.2017
• Subjects: Angiogenesis Inducing Agents; Animals; Cell Proliferation; Cell Survival; drug‐releasing hydrogel; Female; Gelatin - chemistry; gelatin hydrogels; Human Umbilical Vein Endothelial Cells; Humans; Hydrogels - chemistry; Neovascularization, Physiologic; nerve regeneration; Nerve Regeneration - physiology; peripheral nerve; Peripheral Nerves - metabolism; Rats; Rats, Wistar; Regenerative medicine; Schwann Cells - drug effects; Tissue engineering; Tissue Engineering - methods; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; tissue engineering; nerve regeneration; peripheral nerve; gelatin hydrogels; vascular endothelial growth factor; drug-releasing hydrogel
• ISSN: 1932-6254; 1932-7005
• DOI: 10.1002/term.1936

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.