Xu Zi-Xing, Zhang Li-Qun, Wang Chang-Sheng, Chen Rong-Sheng, Li Gui-Shuang, Guo Yu, Xu Wei-Hong
Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005. China.
Curr Neurovasc Res. 2017;14(3):274-289. doi: 10.2174/1567202614666170718093508.
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.
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<sub>165</sub>. The poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulating VEGF<sub>165</sub> 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<sub>165</sub> 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.
VEGF<sub>165</sub> was entrapped with high efficiency (90.8±3.1) %. In vitro VEGF<sub>165</sub> 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.
The results indicate that progress of vascular reconstruction is accelerated in the V-ASCS implanted SCI rats.
促进血管生成提供了一种治疗脊髓损伤（SCI）的可能方法。血管内皮生长因子（VEGF）是一种促血管生成物质，参与内皮细胞（EC）的增殖、迁移和存活。最近发现，向脊髓损伤中心外源性施用VEGF是促进血管芽生的一种潜在方法。
建立大鼠脊髓半切模型，通过植入持续递送VEGF165的脱细胞脊髓支架（ASCS）研究血管生成。基于乳液和溶剂蒸发法制备包裹VEGF165的聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒（NPs），并通过京尼平（GP）交联技术与ASCS偶联。所得支架标记为V-ASCS。通过紫外吸收测量确定VEGF165的包封率（EE）和释放动力学。通过高分辨率微型计算机断层扫描（micro-CT）观察血管生成和血管重塑，并通过血管形态计量参数进行定量分析。进一步研究脊髓组织学和Basso、Beattie和Bresnahan（BBB）运动评分量表。
VEGF165的包封率很高，为（90.8±3.1）%。体外VEGF165释放动力学研究表明，在前24小时内，初始突释量分别为1.966μg mg NPs-1和1.045μg mg V-ASCS-1。在持续释放阶段，每天约有0.040μg mg NPs-1和0.022μg mg V-ASCS-1持续释放，直至720小时。在大鼠脊髓半切模型中，在损伤部位植入V-ASCS可促进脊髓损伤后的血管生成和血管重塑。组织学上可以证实有更好的结果。然而，在动物模型中功能改善有限。
结果表明，植入V-ASCS的脊髓损伤大鼠的血管重建进程加快。
