Vascular endothelial growth factor‐loaded injectable hydrogel enhances plasticity in the injured spinal cord

Abstract

We hypothesized that VEGF-containing hydrogels that gelify in situ following injection into a traumatized spinal cord, could stimulate spinal cord regeneration.Injectable hydrogels composed of 0.5% 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 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.

Transplantation of testicular tissue in alginate hydrogel loaded with VEGF nanoparticles improves spermatogonial recovery

“…Sustained VEGF release from biodegradable and biocompatible hydrogels could be an efficient solution to reduce ischemic stress, especially during the first days following transplantation, and to better preserve testicular tissue potential. Encapsulation of VEGF in chitosan/dextran sulfate-nanoparticle (NP) [20], followed by their incorporation in an alginate hydrogel, ensured sustained VEGF release for over one month [21]. In addition, VEGF-NP-loaded hydrogels induced more pronounced angiogenesis than free VEGF-loaded hydrogels [22].…”

Biomaterials for Local, Controlled Drug Delivery to the Injured Spinal Cord

“…This exposes polymerization sites, enabling fibrin monomers to polymerize into hydrogel form (Li et al, 2015). Through reduction of thrombin concentration (to create a partially solidified hydrogel) or through inclusion of a co-polymer such as alginate (that can interrupt fibrinogen chain entanglement), fibrin hydrogels may be injected into the SCI site (Straley et al, 2010; Sharp et al, 2012; des Rieux et al, 2014). Fibrin is advantageous as it is degraded naturally.…”

Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury

“…Multiple studies have utilized engineered hydrogels to release neurotrophins and growth factors directly into the SCI lesion and demonstrated supplementary exogenous neurotrophins such as NT-3, VEGF, GDNF, NGF, and BDNF could facilitate locomotive recovery in SCI (96, 97). Compared with commonly used methods such as direct injection, systemic administration and intrathecal infusion, hydrogels are able to provide a sustained and tunable release of loaded growth factors (98, 99). Hydrogels are promising carriers for controlled drug release, yet investigation about their long-term safety and biocompatibility after implantation is needed for further clinical application.…”