Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation
Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation
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DOI：
10.1016/j.biomaterials.2015.08.049
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发表时间：
2015-12-01
期刊：
影响因子：
14
通讯作者：
Brey, Eric M.
中科院分区：
文献类型：
--
作者：
Akar, Banu;Jiang, Bin;Brey, Eric M.
可溶性因子的衍生物在包括血管组装在内的许多生物过程中起重要作用。可以在体外详细地研究因子，但是能够在体内研究空间分布的可溶性因子和多细胞过程的方法是有限的。在这里，我们报告了一种在三维（3D）生物材料系统中产生持续体内生长因子梯度的方法。使用颗粒沥滤法制备了载纤维素的多孔聚（乙二醇）（PEG）支架。将血小板衍生生长因子BB（PDGF-BB）包封在聚（乳酸-共-乙醇酸）（PLGA）微球中，将其置于组织材料界面的远端。PLGA提供PDGF-BB的持续释放，并且其通过多孔结构的扩散导致梯度形成。使用近红外荧光成像在体内确认支架内的细胞，并且梯度存在超过3周。PDGF-BB的扩散进行了建模，并在体内成像结果进行了验证。组织侵入的深度和响应于生物材料形成的血管的密度随着梯度的大小而增加。该生物材料系统允许产生持续的生长因子梯度，用于研究体内组织对梯度的反应。爱思唯尔有限公司出版
Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro, but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here, we report on a method for the generation of persistent in vivo gradients of growth factors in a three-dimensional (3D) biomaterial system. Fibrin loaded porous poly (ethylene glycol) (PEG) scaffolds were generated using a particulate leaching method. Platelet derived growth factor BB (PDGF-BB) was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres which were placed distal to the tissue material interface. PLGA provides sustained release of PDGF-BB and its diffusion through the porous structure results in gradient formation. Gradients within the scaffold were confirmed in vivo using near-infrared fluorescence imaging and gradients were present for more than 3 weeks. The diffusion of PDGF-BB was modeled and verified with in vivo imaging findings. The depth of tissue invasion and density of blood vessels formed in response to the biomaterial increased with magnitude of the gradient. This biomaterial system allows for generation of sustained growth factor gradients for the study of tissue response to gradients in vivo. Published by Elsevier Ltd.