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

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 mu g mg NPs(-1) and 1.045 mu g mg V-ASCS(-1) respectively in the first 24 hours. In the phase of sustained release, approximately 0.040 mu g mg NPs(-1) and 0.022 mu g 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.