Vascular endothelial growth factor and fibroblast growth factor 2 delivery from spinal cord bridges to enhance angiogenesis following injury

Abstract

The host response to spinal cord injury can lead to an ischemic environment that can induce cell death and limits cell transplantation approaches to promote spinal cord regeneration. Spinal cord bridges that provide a localized and sustained release of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) were investigated for their ability to promote angiogenesis and nerve growth within the injury. Bridges were fabricated by fusion of poly(lactide-co-glycolide) microspheres using a gas foaming/particulate leaching technique, and proteins were incorporated by encapsulation into the microspheres and/or mixing with the microspheres before foaming. Compared to the mixing method, encapsulation reduced the losses during leaching and had a slower protein release, while VEGF was released more rapidly than FGF-2. In vivo implantation of bridges loaded with VEGF enhanced the levels of VEGF within the injury at 1 week, and bridges releasing VEGF and FGF-2 increased the infiltration of endothelial cells and the formation of blood vessel at 6 weeks postimplantation. Additionally, substantial neurofilament staining was observed within the bridge; however, no significant difference was observed between bridges with or without protein. Bridges releasing angiogenic factors may provide an approach to overcome an ischemic environment that limits regeneration and cell transplantation-based approaches.