Host immune competence and local ischemia affects the functionality of engineered vasculature
Host immune competence and local ischemia affects the functionality of engineered vasculature
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DOI：
10.1080/10739680601131101
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发表时间：
2007-02-01
期刊：
影响因子：
2.4
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
--
作者：
Chen, Ruth R.;Snow, Jonathan K.;Mooney, David J.
目的：血管内皮生长因子（VEGF）的局部和持续递送是克服推注递送的有限功效的有前途的方法。作者研究了宿主免疫能力和局部缺血对用这种方法形成的新血管网络功能的影响。方法：血管结构和灌注导致多孔85：15聚乙烯前植入在免疫活性C57 BL/6和免疫缺陷：SCID小鼠的皮下组织和缺血后肢中测量释放VEGF（165）的（丙交酯-共-乙交酯）支架。持续的VEGF递送导致两个植入部位和两种动物模型中支架内血管密度增加相似至100%。然而，与对照相比，植入皮下组织中的支架内的所得灌注适度增加（18-35%），而当将VEGF释放支架放置在C57 BL/6或SCID小鼠的缺血后肢中时，灌注比对照增加52-110%。在SCID小鼠中，VEGF递送改善了整个缺血肢体中的灌注（到第6周为正常值的55 +/-18%;比对照增加138%）。虽然C57 BL/6小鼠表现出自发恢复前缺血，VEGF交付加速恢复相比，control.Conclusions：局部和持续的VEGF交付可以创建功能性血管：放大恢复组织缺血。然而，局部和区域灌注的增加高度依赖于植入部位和动物模型。
Objective: Localized and sustained delivery of vascular endothelial growth factor (VEGF) is a promising approach to overcome the limited efficacy of bolus delivery. The authors examined the effects of host immune competence and local ischemia on the functionality of new vessel networks formed with this approach.Methods: Vessel structure and perfusion resulting front implantation of porous 85:15 poly(lactide-co-glycolide) scaffolds releasing VEGF(165) were measured in both subcutaneous tissue and ischemic hindlimbs of immune competent C57BL/6 and immune deficient: SCID mice.Results: Sustained VEGF delivery resulted in a similar similar to 100% increase in vessel density within Scaffolds in both implant sites; and both animal models. However, the resulting perfusion within scaffolds implanted in subcutaneous tissue increased modestly versus control (18-35%), while perfusion increased 52-110% above control when VEGF-releasing scaffolds were placed in ischemic hindlimbs of C57BL/6 or SCID mice. VEGF delivery unproved perfusion in the entire ischemic limb (55 +/- 18% of die normal value by week 6; 138% increase over control) in SCID mice. Although C57BL/6 mice demonstrated spontaneous recovery front ischemia, VEGF delivery accelerated recovery as compared to control.Conclusions: Localized and sustained VEGF delivery can create functional vasculature that: amplifies recovers of tissue ischemia. However; increases in local and regional perfusion were highly dependent on the implantation site and the animal model.