Evaluation of blood vessel ingrowth in fibrin gel subject to type and concentration of growth factors.
Evaluation of blood vessel ingrowth in fibrin gel subject to type and concentration of growth factors.
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DOI：
10.1111/j.1582-4934.2008.00410.x
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Kneser U
中科院分区：
文献类型：
--
作者：
Arkudas A;Tjiawi J;Saumweber A;Beier JP;Polykandriotis E;Bleiziffer O;Horch RE;Kneser U
我们的目的是在合适的皮下大鼠模型中定量评估固定在基于纤维蛋白的药物递送系统中的 VEGF 和 bFGF 的血管生成效应。在对合适的植入技术（6只大鼠）进行评估后，将四个含有纤维蛋白凝胶基质的聚四氟乙烯隔离室以倒置的方式植入到30只Lewis大鼠的背部皮下。该基质由 500 μl 纤维蛋白凝胶组成，具有两种不同的纤维蛋白原浓度（10 mg/ml 或 40 mg/ml 纤维蛋白原）和 2 I.U./ml 凝血酶，并含有五种不同浓度的 VEGF 和 bFGF（每种浓度为 0 至 250 ng/ml）。植入后3、7和14天，将基质移出并进行组织学和形态测量分析。第 1 周时，与浓度较低的生长因子相比，100 ng/ml 和 250 ng/ml VEGF 和 bFGF 组的纤维蛋白凝块体积明显更小。在第 1 周和第 2 周，与不含生长因子的对照相比，使用低浓度生长因子（25 ng/ml VEGF 和 bFGF）显着增加了纤维血管组织的数量、血管的平均分数以及基质-宿主界面的血管数量。在该模型中，较高的浓度既不与组织形成的进一步增加相关，也不与血管萌芽的增加相关。这项研究表明，在新开发的皮下颠倒隔离室模型中，纤维蛋白凝胶固定的血管诱导生长因子可有效刺激纤维血管组织的生成和血管的萌芽，最佳剂量在 25 至 100 ng/ml 之间。
Our aim was to quantitatively assess the angiogenetic effects of VEGF and bFGF immobilized in a fibrin-based drug delivery system in a suitable subcutaneous rat model. After evaluation of a suitable implantation technique (6 rats), four teflon isolation chambers containing fibrin gel matrices were implanted subcutaneously in an upside-down fashion on the back of 30 Lewis rats. The matrices consisted of 500 μl fibrin gel with two different fibrinogen concentrations (10 mg/ml or 40 mg/ml fibrinogen) and 2 I.U./ml thrombin and contained VEGF and bFGF in five different concentrations (0 to 250 ng/ml each). At 3, 7 and 14 days after implantation, matrices were explanted and subjected to histological and morphometrical analysis. At 1 week, the volume of the fibrin clots was significantly smaller in the 100 and 250 ng/ml VEGF and bFGF groups in comparison to lower concentrated growth factors. At 1 and 2 weeks, the use of growth factors in low concentrations (25 ng/ml VEGF and bFGF) significantly increased the amount of fibrovascular tissue, average fraction of blood vessels and number of blood vessels at the matrix–host interface in comparison to growth factor-free controls. Higher concentrations were neither associated with further increase of tissue formation nor with increased sprouting of blood vessels in this model. This study demonstrates that fibrin gel-immobilized angioinductive growth factors efficiently stimulate generation of fibrovascular tissue and sprouting of blood vessels in a newly developed subcutaneous upside-down isolation chamber model with an optimum between 25 and 100 ng/ml.
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影响因子：
5.3
作者：
Fiegel HC;Kaufmann PM;Bruns H;Kluth D;Horch RE;Vacanti JP;Kneser U
通讯作者：
Kneser U
影响因子：
2.4
作者：
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Gitnick, T
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作者：
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Francis, CW
影响因子：
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作者：
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通讯作者：
Turina, M
影响因子：
2.3
作者：
Wilcke, I.;Lohmeyer, J. A.;Machens, H. G.
通讯作者：
Machens, H. G.