Hydrogels are promising materials in regenerative medicine applications due to their hydrophilicity, biocompatibility and capability 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 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. Hydrogel preparation process was optimized to allow VEGF functional incorporation, 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 (HUVEC) 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 proving confirmation that released VEGF maintained its effect, as also confirmed in tubulogenesis assay. In conclusion, a gelatin based hydrogel system for bioactive VEGF delivery was developed and characterized for its applicability in neural tissue engineering.
Hydrogel mediated delivery of Vascular Endothelial Growth Factor for peripheral nerve regeneration.
DI BLASIO, LAURA;PRIMO, Luca;GAMBAROTTA, Giovanna;GEUNA, Stefano;PERROTEAU, Isabelle;GNAVI, SARA
2014-01-01
Abstract
Hydrogels are promising materials in regenerative medicine applications due to their hydrophilicity, biocompatibility and capability 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 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. Hydrogel preparation process was optimized to allow VEGF functional incorporation, 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 (HUVEC) 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 proving confirmation that released VEGF maintained its effect, as also confirmed in tubulogenesis assay. In conclusion, a gelatin based hydrogel system for bioactive VEGF delivery was developed and characterized for its applicability in neural tissue engineering.
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