Effects of VEGF loading on scaffold-confined vascularization
Effects of VEGF loading on scaffold-confined vascularization
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DOI：
10.1002/jbm.a.32902
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发表时间：
2010-12-01
影响因子：
4.9
通讯作者：
Ruecker, Martin
中科院分区：
文献类型：
--
作者：
Lindhorst, Daniel;Tavassol, Frank;Ruecker, Martin
组织工程结构的充分血管化仍然是骨移植的主要挑战。有鉴于此，我们通过胶原涂层将血管内皮生长因子（VEGF）负载于β-磷酸三钙（β-TCP）和多孔聚（L-丙交酯-共-乙交酯）（PLGA）支架，并研究VEGF负载是否改善支架血管生成和血管化。将背侧皮褶腔植入48只balb/c小鼠，将其分为6组（每组n = 8）。将未包被的（对照）、胶原包被的以及另外加载VEGF的PLGA和β-TCP支架插入腔室中。在14天的观察期内，使用活体荧光显微镜反复分析血管生成、新血管形成和白细胞-内皮细胞相互作用。此外，通过ELISA研究了PLGA和β-TCP支架的VEGF释放。从组织学标本的微形态学进行了研究。与未加载的PLGA支架相比，未加载的β-TCP支架显示出加速和增加的血管生成反应。在体外，与β-TCP相比，PLGA在前两天释放显著更高量的VEGF，导致在随后的几天释放量快速下降，直至第7天，其中VEGF释放可忽略不计。尽管如此，体内VEGF负载增加了新血管形成，特别是在β-TCP支架中。这种增加的血管形成与第3天和第6天的暂时性白细胞反应以及明显的白细胞-内皮细胞相互作用相关。组织学显示β-TCP和PLGA支架均具有足够的宿主组织反应和植入。我们的研究表明，β-TCP支架比PLGA支架提供更合适的血管化条件，特别是如果它们装载有VEGF。(C)2010 Wiley Periodicals，Inc. J Biomed Mater Res Part A：95A：783-792，2010.
Adequate vascularization of tissue-engineered constructs remains a major challenge in bone grafting. In view of this, we loaded beta-tricalcium-phosphate (beta-TCP) and porous poly(L-lactide-co-glycolide) (PLGA) scaffolds via collagen coating with vascular endothelial growth factor (VEGF) and studied whether the VEGF loading improves scaffold angiogenesis and vascularization. Dorsal skinfold chambers were implanted into 48 balb/c mice, which were assigned to 6 groups (n = 8 each). Uncoated (controls), collagen-coated, and additionally VEGF-loaded PLGA and beta-TCP scaffolds were inserted into the chambers. Angiogenesis, neovascularization, and leukocyte-endothelial cell interaction were analyzed repeatedly during a 14-day observation period using intravital fluorescence microscopy. Furthermore, VEGF release from PLGA und beta-TCP scaffolds was studied by ELISA. Micromorphology was studied from histological specimens. Unloaded beta-TCP scaffolds showed an accelerated and increased angiogenic response when compared with unloaded PLGA scaffolds. In vitro, PLGA released significantly higher amounts of VEGF compared with beta-TCP at the first two days resulting in a rapid drop of the released amount at the following days up to day 7 where the VEGF release was negligible. Nonetheless, in vivo VEGF loading increased neovascularization, especially in beta-TCP scaffolds. This increased vascularization was associated with a temporary leukocytic response with pronounced leukocyte-endothelial cell interaction at days 3 and 6. Histology revealed adequate host tissue response and engraftment of both beta-TCP and PLGA scaffolds. Our study demonstrates that beta-TCP scaffolds offer more suitable conditions for vascularization than PLGA scaffolds, in particular if they are loaded with VEGF. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 95A: 783-792, 2010.