Title:Acellular Spinal Cord Scaffold Implantation Promotes Vascular Remodeling with Sustained Delivery of VEGF in a Rat Spinal Cord Hemisection Model
Volume: 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*
Affiliation:
- Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005,China
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.
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 VEGF
165.
The poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulating VEGF
165 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. VEGF
165
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: VEGF
165 was entrapped with high efficiency (90.8±3.1) %. In vitro VEGF
165 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
