Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL hydrogel in rats.

Bo Chen,Qian Zhang,Xian Zhang,Lingling Zhang,Rui Zhang,En Xie,Yi Wang,Jianyu He,Cuicui Liu,Dingjun Hao,Linhong Huang,Hao Yang

doi:10.1038/srep09017

Bo Chen, Qian Zhang + Show 10 more

Open Access

https://doi.org/10.1038/srep09017

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Abstract

There is no effective strategy for the treatment of spinal cord injury (SCI). An appropriate combination of hydrogel materials and neurotrophic factor therapy is currently thought to be a promising approach. In this study, we performed experiments to evaluate the synergic effect of implanting hydroxyl ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL) hydrogel incorporated with basic fibroblast growth factor (bFGF) into the site of surgically induced SCI. Prior to implantation, the combined hydrogel was surrounded by an acellular vascular matrix. Sprague–Dawley rats underwent complete spinal cord transection at the T-9 level, followed by implantation of bFGF/HEMA-MOETACL 5 days after transection surgery. Our results showed that the bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating tissue eight weeks after implantation. Furthermore, this newly designed implant promoted both nerve tissue regeneration and functional recovery following SCI. These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for intrathecal, localized and sustained delivery of bFGF to the injured spinal cord and provide evidence for the possibility that this approach may have clinical applications in the treatment of SCI.

Highlights

There is no effective strategy for the treatment of spinal cord injury (SCI)
We performed experiments to evaluate the synergic effect of implanting hydroxyl ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL) hydrogel incorporated with basic fibroblast growth factor into the site of surgically induced SCI
Blood flow in the spinal cord is acutely impacted after SCI when vasoconstriction occurs due to factors that are released after immediate cell death as well as through the process of angiogenesis. basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factors (FGFs) which regulate a variety of biological functions including neuroprotection, vasodilation, stimulating angiogenesis and suppressing cell apoptosis11–13. bFGF is abundantly expressed in the nervous system, where it has vital roles, and was previously shown to support the survival and growth of neurons and neural stem cells in vitro[14]

Summary

Introduction

There is no effective strategy for the treatment of spinal cord injury (SCI). An appropriate combination of hydrogel materials and neurotrophic factor therapy is currently thought to be a promising approach. Our results showed that the bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating tissue eight weeks after implantation This newly designed implant promoted both nerve tissue regeneration and functional recovery following SCI. These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for intrathecal, localized and sustained delivery of bFGF to the injured spinal cord and provide evidence for the possibility that this approach may have clinical applications in the treatment of SCI. The unimmunogenic GAG can absorb growth factors and cytokines, promoting the adhesion and migration of cells; elastic and collagen fibers can provide mechanical support for the ingrowth of tissue inside the hydrogel This bFGF/HEMA-MOETACL transplant was implanted into the lesion 5 days after transection surgery. Our results indicate that the bFGF/HEMA-MOETACL transplant is a promising scaffold for nerve tissue regeneration and functional recovery of essentially paralyzed hindlimbs in SCI

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