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Acellular Spinal Cord Scaffold Implantation Promotes Vascular Remodeling with Sustained Delivery of VEGF in a Rat Spinal Cord Hemisection Model

[ Vol. 14 , Issue. 3 ]

Author(s):

Zi-Xing Xu, Li-Qun Zhang, Chang-Sheng Wang, Rong-Sheng Chen, Gui-Shuang Li, Yu Guo and Wei-Hong Xu*   Pages 274 - 289 ( 16 )

Abstract:


Background: Promoting angiogenesis provides a possible therapeutic approach in treating spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a pro-angiogenic substance that is involved in endothelial cell (EC) proliferation, migration, and survival. Exogenous administration of VEGF to the lesion epicenter of the spinal cord has been recently revealed as a potential method for promoting the blood vessel sprouting.

Methods: Spinal cord hemisection in a rat model was established and angiogenesis was studied through implant of an acellular spinal cord scaffold (ASCS) with sustained delivery of VEGF165. The poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulating VEGF165 were fabricated on basis of an emulsion and solvent evaporation method and conjugated to ASCS by a Genipin (GP) crosslinking technology. The resultant scaffolds were marked as V-ASCS. VEGF165 entrapment efficiency (EE) and released kinetics were determined by an ultraviolet absorption measurement. Angiogenesis and vascular remodeling were observed via a high-resolution micro-CT and analyzed quantitatively by vascular morphometric parameters. Spinal cord histology and Basso, Beattie, and Bresnahan (BBB) locomotor rating scale were further studied.

Results: VEGF165 was entrapped with high efficiency (90.8±3.1) %. In vitro VEGF165 release kinetics study showed an initial burst of 1.966 μg mg NPs-1 and 1.045μg mg V-ASCS-1 respectively in the first 24 hours. In the phase of sustained release, approximately 0.040μg mg NPs-1 and 0.022μg mg V-ASCS-1 per day was on-going until 720h. In the rat spinal cord hemisection model, implant of V-ASCS at the injured site showed a promotion of angiogenesis and vascular remodeling following SCI. A better outcome can be confirmed histologically. However, functional improvement is limited in the animal model.

Conclusion: The results indicate that progress of vascular reconstruction is accelerated in the V-ASCS implanted SCI rats. Keywords: Spinal cord injury (SCI), acellular spinal cord

Keywords:

Spinal cord injury (SCI), acellular spinal cord scaffold (ASCS), vascular endothelial growth factor (VEGF), poly (lactic-co-glycolic acid) (PLGA) nano-particles, sustained delivery system, vascular remodeling.

Affiliation:

Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005



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