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用于组织工程应用的具有可控孔隙率的大孔互连葡聚糖支架。

Macroporous interconnected dextran scaffolds of controlled porosity for tissue-engineering applications.

作者信息

Lévesque Stéphane G, Lim Ryan M, Shoichet Molly S

机构信息

Department of Chemical Engineering and Applied Chemistry, Toronto, Ont., Canada M5S 3E5.

出版信息

Biomaterials. 2005 Dec;26(35):7436-46. doi: 10.1016/j.biomaterials.2005.05.054.

Abstract

Dextran hydrogels have been studied as drug delivery vehicles but not as scaffolds for tissue-engineering likely because previously synthesized dextran hydrogels had pores too small for cell penetration. Our goal was to create macroporous, interconnected dextran scaffolds. To this end, we took advantage of the liquid-liquid immiscibility of poly(ethylene glycol) and methacrylated dextran during radical crosslinking of the methacrylated moieties. By controlling the degree of methacrylate substitution on dextran, dextran molar mass and PEG concentration, macroporous hydrogels were created. The presence of PEG in solution had a significant effect on the final morphology of the dextran hydrogel leading to the formation of different types of structures, from microporous gel to macroporous gel-wall to a macroporous interconnected-beaded structure. A series of formulation diagrams were prepared which allowed us to determine which conditions led to the formation of macroporous interconnected-beaded scaffolds. Dextran macroporous interconnected-beaded gels had a high water content, between 89% and 94%, a homogeneous morphology, determined by scanning electron microscopy, with interconnected macroporous pores, as determined by protein diffusivity where the effective diffusion coefficients of BSA were calculated to be 3.1 x 10(-7)cm2/s for Dex-MA 40 kDa DS 5 and 1 x 10(-7)cm2/s for Dex-MA 6 kDa DS10, which are similar to that of BSA in water, 5.9 x 10(-7)cm2/s. Mercury intrusion porosimetry showed that the macroporous interconnected-beaded scaffolds had a bimodal distribution of macropores, with a median diameter of 41 microm, interconnected by throats, which had a median diameter of 11 microm. Together, these data suggest that the dextran scaffolds will be advantageous in applications that require an interconnected macroporous geometry, such as those of tissue engineering where cell penetration and nutrient diffusion are necessary for tissue regeneration.

摘要

葡聚糖水凝胶已被作为药物递送载体进行研究,但尚未作为组织工程支架进行研究,这可能是因为先前合成的葡聚糖水凝胶的孔隙太小,细胞无法穿透。我们的目标是创建大孔、相互连接的葡聚糖支架。为此,我们利用了聚乙二醇和甲基丙烯酸化葡聚糖在甲基丙烯酸化部分的自由基交联过程中的液-液不相容性。通过控制葡聚糖上甲基丙烯酸酯的取代度、葡聚糖摩尔质量和聚乙二醇浓度,制备出了大孔水凝胶。溶液中聚乙二醇的存在对葡聚糖水凝胶的最终形态有显著影响,导致形成不同类型的结构,从微孔凝胶到大孔凝胶壁再到大孔相互连接的珠状结构。制备了一系列配方图,使我们能够确定哪些条件会导致形成大孔相互连接的珠状支架。葡聚糖大孔相互连接的珠状凝胶含水量高,在89%至94%之间,通过扫描电子显微镜确定其形态均匀,具有相互连接的大孔孔隙,通过蛋白质扩散率确定,其中牛血清白蛋白的有效扩散系数对于40 kDa DS 5的葡聚糖甲基丙烯酸酯计算为3.1×10(-7)cm2/s,对于6 kDa DS10的葡聚糖甲基丙烯酸酯计算为1×10(-7)cm2/s,这与牛血清白蛋白在水中的扩散系数5.9×10(-7)cm2/s相似。压汞法显示,大孔相互连接的珠状支架具有双峰分布的大孔,中值直径为41微米,由中值直径为11微米的喉道相互连接。总之,这些数据表明,葡聚糖支架在需要相互连接的大孔几何形状的应用中具有优势,例如在组织工程中,细胞穿透和营养物质扩散对于组织再生是必要的。

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