Angiogenic and inflammatory response to biodegradable scaffolds in dorsal skinfold chambers of mice

Angiogenic and inflammatory response to biodegradable scaffolds in dorsal skinfold chambers of mice
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DOI:
10.1016/j.biomaterials.2006.05.033
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发表时间:
2006-10-01
期刊:
影响因子:
14
通讯作者:
Menger, Michael D.
Menger, Michael D.
中科院分区:
工程技术1区
文献类型:
--
作者:
Ruecker, Martin;Laschke, Matthias W.;Menger, Michael D.

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对于组织工程,支架应具有生物相容性并促进新血管形成。由于对这些特定性质知之甚少,我们在此研究了植入常用支架材料后的体内宿主血管生成和炎症反应。将聚L-丙交酯-乙交酯共聚物(PLGA)和胶原-壳聚糖-羟基磷灰石多孔水凝胶支架植入balb/c小鼠背部皮褶腔。其他动物接受皮质骨作为同基因生物植入物,而没有植入物的动物的腔室作为对照。使用活体荧光显微镜在14天内分析血管生成和新血管形成以及白细胞-内皮细胞相互作用和微血管通透性。与对照相比,PLGA支架显示白细胞募集略有增加。这与微血管通透性的升高有关,这与在同基因骨组织中观察到的情况相当。值得注意的是,PLGA诱导了显著的血管生成反应,揭示了新形成的毛细血管的密度几乎与骨植入物中观察到的相似。组织学显示巨噬细胞浸润,可能表明生物材料吸收。相比之下,水凝胶支架诱导严重的炎症,如通过白细胞-内皮细胞相互作用的类似15倍增加和微血管通透性的显著升高所指示的。这与诱导周围组织内的凋亡细胞死亡和完全缺乏新形成的微血管向内生长有关。组织学证实PLGA和等基因骨充分植入宿主组织,但水凝胶未植入。PLGA支架显示出比水凝胶支架更好的生物相容性,并促进血管向内生长,保证在宿主组织内充分植入。(c)2006爱思唯尔有限公司保留所有权利。
For tissue engineering, scaffolds should be biocompatible and promote neovascularization. Because little is known on those specific properties, we herein studied in vivo the host angiogenic and inflammatory response after implantation of commonly used scaffold materials. Porous Poly(L-lactide-co-glycolide) (PLGA) and collagen-chitosan-hydroxyapatite hydrogel scaffolds were implanted into dorsal skinfold chambers of balb/c mice. Additional animals received cortical bone as an isogeneic, biological implant, while chambers of animals without implants served as controls. Angiogenesis and neovascularization as well as leukocyte-endothelial cell interaction and microvascular permeability were analyzed over 14 day using intravital fluorescence microscopy. PLGA scaffolds showed a slight increase in leukocyte recruitment compared to controls. This was associated with an elevation of microvascular permeability, which was comparable to that observed in isogeneic bone tissue. Of interest, PLGA induced a marked angiogenic response, revealing a density of newly formed capillaries almost similar to that observed in bone implants. Histology showed infiltration of macrophages, probably indicating resorption of the biomaterial. In contrast, hydrogel scaffolds induced a severe inflammation, as indicated by an similar to 15-fold increase of leukocyte-endothelial cell interaction and a marked elevation of microvascular permeability. This was associated by induction of apoptotic cell death within the surrounding tissue and a complete lack of ingrowth of newly formed microvessels. Histology confirmed adequate engraftment of PLGA and isogeneic bone but not hydrogel within the host tissue. PLGA scaffolds show a better biocompatibility than hydrogel scaffolds and promote vascular ingrowth, guaranteeing adequate engraftment within the host tissue. (c) 2006 Elsevier Ltd. All rights reserved.