des Rieux Anne, De Berdt Pauline, Ansorena Eduardo, Ucakar Bernard, Damien Jacobs, Schakman Olivier, Audouard Emilie, Bouzin Caroline, Auhl Dietmar, Simón-Yarza Teresa, Feron Olivier, Blanco-Prieto Maria J, Carmeliet Peter, Bailly Christian, Clotman Fréderic, Préat Véronique
Pharmaceutics and Drug delivery Unit, Louvain Drug Research Institute, Université catholique de Louvain, 1200, Brussels, Belgium.
J Biomed Mater Res A. 2014 Jul;102(7):2345-55. doi: 10.1002/jbm.a.34915. Epub 2013 Aug 30.
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.
我们推测，注射到创伤脊髓后原位凝胶化的含血管内皮生长因子（VEGF）水凝胶能够刺激脊髓再生。使用了由0.5%普诺那UPMVG MVG海藻酸盐组成、添加或不添加纤维蛋白原的可注射水凝胶。向海藻酸盐中添加纤维蛋白原对体外细胞增殖没有影响，但在体外支持神经突生长。当在大鼠脊髓半切模型中注射时，添加纤维蛋白原的海藻酸盐耐受性良好。掺入水凝胶中的VEGF的释放受VEGF制剂[封装在微球、纳米颗粒或溶液（游离）中]的影响。游离VEGF和负载VEGF的纳米颗粒的组合与海藻酸盐：纤维蛋白原混合并注射到脊髓损伤部位。注射后四周，与单独的水凝胶相比，血管生成和神经突生长增加。基于可注射海藻酸盐：纤维蛋白原的水凝胶局部递送VEGF在损伤脊髓中诱导了一些可塑性，涉及纤维向损伤部位生长。
