Sustained release of multiple growth factors from injectable polymeric system as a novel therapeutic approach towards angiogenesis.
Sustained release of multiple growth factors from injectable polymeric system as a novel therapeutic approach towards angiogenesis.
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DOI：
10.1007/s11095-009-0014-0
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发表时间：
2010-02
影响因子：
3.7
通讯作者：
Rajagopalan, Sanjay
中科院分区：
文献类型：
--
作者：
Sun, Qinghua;Silva, Eduardo A.;Wang, Aixia;Fritton, James C.;Mooney, David J.;Schaffler, Mitchell B.;Grossman, Paul M.;Rajagopalan, Sanjay
目的是研究生物可降解的藻酸盐和聚乳酸-共-乙交酯（PLG）系统能够提供生长因子顺序将上级单一的生长因子输送促进新血管形成和改善灌注。三组apoE敲除小鼠接受单侧后肢缺血手术，并接受缺血肢体肌肉内注射藻酸盐（空白）、含VEGF 165的藻酸盐（VEGF）或含VEGF 165的藻酸盐与含PDGF-BB的PLG微球的组合（VEGF/PDGF）。通过形态学和免疫组化终点评估缺血后肢的血管分布，同时通过激光多普勒血流灌注指数评估血流变化。在多个时间点评估肌肉VEGF和PDGF含量。在VEGF/PDGF组中，局部组织VEGF和PDGF水平分别在第2周和第4周达到峰值，第6周可检测到PDGF水平。第6周时，VEGF/PDGF组的平均血管平均直径显著大于VEGF组或空白组，有证据表明形成良好的平滑肌衬里小动脉。使用可注射的、可生物降解的平台顺序递送VEGF和PDGF导致灌注的稳定和持续改善。这种缓释、控释、可注射的藻酸盐聚合物系统是一种有前途的多种生长因子递送的临床应用方法。
The aim was to investigate that a bio-degradable alginate and poly lactide-co-glycolide (PLG) system capable of delivering growth factors sequentially would be superior to single growth factor delivery in promoting neovascularization and improving perfusion. Three groups of apoE null mice underwent unilateral hindlimb ischemia surgery and received ischemic limb intramuscular injections of alginate (Blank), alginate containing VEGF165 (VEGF), or alginate containing VEGF165 combined with PLG microspheres containing PDGF-BB (VEGF/PDGF). Vascularity in the ischemic hindlimb was assessed by morphologic and immunohistochemical end-points, while changes in blood flow were assessed by Laser Doppler Perfusion Index. Muscle VEGF and PDGF content was assessed at multiple time points. In the VEGF/PDGF group, local tissue VEGF and PDGF levels peaked at week 2 and 4, respectively, with detectable PDGF levels at week 6. At week 6, mean vessel mean diameter was significantly greater in the VEGF/PDGF group compared to the VEGF or Blank groups with evidence of well-formed smooth muscle-lined arterioles. Sequential delivery of VEGF and PDGF using an injectable, biodegradable platform resulted in stable and sustained improvements in perfusion. This sustained, control-released, injectable alginate polymer system is a promising approach for multiple growth factor delivery in clinical application.
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影响因子：
37.8
作者：
Sun Q;Yue P;Deiuliis JA;Lumeng CN;Kampfrath T;Mikolaj MB;Cai Y;Ostrowski MC;Lu B;Parthasarathy S;Brook RD;Moffatt-Bruce SD;Chen LC;Rajagopalan S
通讯作者：
Rajagopalan S
影响因子：
64.8
作者：
Yancopoulos, GD;Davis, S;Holash, J
通讯作者：
Holash, J
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW
影响因子：
37.8
作者：
Couffinhal, T;Silver, M;Isner, JM
通讯作者：
Isner, JM
影响因子：
37.8
作者：
Henry, TD;Annex, BH;McCluskey, ER
通讯作者：
McCluskey, ER