VEGF165 and bFGF protein-based therapy in a slow release system to improve angiogenesis in a bioartificial dermal substitute in vitro and in vivo
VEGF165 and bFGF protein-based therapy in a slow release system to improve angiogenesis in a bioartificial dermal substitute in vitro and in vivo
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DOI：
10.1007/s00423-007-0194-1
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发表时间：
2007-05-01
影响因子：
2.3
通讯作者：
Machens, H. G.
中科院分区：
文献类型：
--
作者：
Wilcke, I.;Lohmeyer, J. A.;Machens, H. G.
背景 血管生成可通过多种生长因子增强，例如血管内皮生长因子-165 (VEGF(165)) 和碱性成纤维细胞生长因子 (bFGF)。通过将生长因子掺入纤维蛋白基质中可以延迟释放此类生长因子。在这项研究中，我们提出了一种在纤维蛋白密封剂中缓慢释放VEGF(165)和bFGF的系统。材料和方法体外：制备直径15mm的Integra(TM)基质片。 Integra (TM) 基质分为四组（A=对照；B=纤维蛋白密封剂；C=纤维蛋白密封剂+生长因子；D=生长因子）。体内：将生物人工真皮模板移植到 nu-nu 小鼠背部的全皮缺损处。四个不同的组在第2周和第4周时分别包含六个基质。 体外结果：在C组和D组中，VEGF(165)和bFGF的持续释放是显着的。将生长因子掺入纤维蛋白密封剂中会引起生长因子释放延长（p < 0.05）。体内：与 A 组和 B 组相比，C 组和 D 组的血管数量显着增加 (p < 0.001)。结论 通过将 VEGF(165) 和 bFGF 与纤维蛋白密封剂相结合，产生了缓慢蛋白释放的模型。该模型导致生长因子在体内的生物利用度延长以达到功能目的。纤维蛋白和胶原蛋白可以在体内释放生长因子，并在生物人造真皮模板中诱导显着且更快的新生血管形成。
Background Angiogenesis can be enhanced by several growth factors, like vascular endothelial growth factor-165 (VEGF(165)) and basic fibroblast growth factor (bFGF). Delayed release of such growth factors could be provided by incorporation of growth factors in fibrin matrices. In this study, we present a slow release system for VEGF(165) and bFGF in fibrin sealant.Materials and methods In vitro: Pieces of Integra (TM) matrix of 15 mm in diameter were prepared. Integra (TM) matrices were divided into four groups (A=control; B=fibrin sealant; C=fibrin sealant+growth factors; D=growth factors). In vivo: The bioartificial dermal templates were transplanted into a full-skin defect of the back of nu-nu mice. Four different groups included each six matrices at 2 and 4 weeks.Results In vitro: In groups C and D, continuous release of VEGF(165) and bFGF was eminent. The incorporation of growth factors into fibrin sealant evoked a prolonged growth factor release (p < 0.05). In vivo: A significantly higher amount of vessels was quantified in groups C and D compared to groups A and B (p < 0.001).Conclusions A model of slow protein release by combining VEGF(165) and bFGF with fibrin sealant was produced. This model resulted in a prolonged bioavailability of growth factors in vivo for functional purposes. Fibrin and collagen can release growth factors in vivo and induce significant and faster neovascularisation in bioartificial dermal templates.