Vascular endothelial growth factor-loaded injectable hydrogel enhances plasticity in the injured spinal cord.
We hypothesized that vascular endothelial growth factor (VEGF)-containing hydrogels that gelify in situ after injection into a traumatized spinal cord, could stimulate spinal cord regeneration. Injectable hydrogels composed of 0.5% Pronova UPMVG MVG alginate, supplemented or not with fibrinogen, were used. The addition of fibrinogen to alginate had no effect on cell proliferation in vitro but supported neurite growth ex vivo. When injected into a rat spinal cord in a hemisection model, alginate supplemented with fibrinogen was well tolerated. The release of VEGF that was incorporated into the hydrogel was influenced by the VEGF formulation [encapsulated in microspheres or in nanoparticles or in solution (free)]. A combination of free VEGF and VEGF-loaded nanoparticles was mixed with alginate:fibrinogen and injected into the lesion of the spinal cord. Four weeks post injection, angiogenesis and neurite growth were increased compared to hydrogel alone. The local delivery of VEGF by injectable alginate:fibrinogen-based hydrogel induced some plasticity in the injured spinal cord involving fiber growth into the lesion site.
Pharmaceutics and Drug delivery Unit, Louvain Drug Research Institute, Université catholique de Louvain, 1200, Brussels, Belgium.
Anne
A
des Rieux
Pauline
P
De Berdt
Eduardo
E
Ansorena
Bernard
B
Ucakar
Jacobs
J
Damien
Olivier
O
Schakman
Emilie
E
Audouard
Caroline
C
Bouzin
Dietmar
D
Auhl
Teresa
T
Simón-Yarza
Olivier
O
Feron
Maria J
MJ
Blanco-Prieto
Peter
P
Carmeliet
Christian
C
Bailly
Fréderic
F
Clotman
Véronique
V
Préat
D000818:Animals; D001672:Biocompatible Materials; D020100:Hydrogels; D051379:Mice; D041681:NIH 3T3 Cells; D009473:Neuronal Plasticity; D051381:Rats; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
D001672:Biocompatible Materials; D020100:Hydrogels; D042461:Vascular Endothelial Growth Factor A
VEGF delivery; alginate; injectable hydrogel; microparticles; nanoparticles; spinal cord