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A novel bicomponent, hydrogel-bored, biodegradable polymer fiber for tissue engineering and drug delivery applications.

机译:一种新型的双组分,水凝胶钻孔的,可生物降解的聚合物纤维,用于组织工程和药物输送应用。

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摘要

We have developed a novel biodegradable, polymeric fiber construct that is co-extruded using a wet-spinning process into a core-sheath format with a polysaccharide pre-hydrogel solution as a core fluid. The properties of the gel and the polymer can be modified extensively, resulting in numerous fiber formats that provide a variety of profiles for release of loaded proteins, growth factors, drugs, and other therapeutics. These biologically sensitive agents are protected from denaturation by either their incorporation into the hydrogel, their incorporation as a dispersed phase into a polymeric continuous phase emulsion extruded as the fiber sheath, or through combinations thereof. Multiple agents can be co-loaded in this manner, resulting in a variety of biologically active therapeutic capabilities.; We show that this core-sheath fiber format will load a model protein that can be delivered for extended periods in vitro. The biodegradable, biocompatible fibers were extruded from polymeric emulsions comprised of solutions of various molecular weights of poly(L-lactic acid) (PLLA) dissolved in chloroform and containing dispersed, protein-free aqueous phases comprising up to 10% of the emulsion volume. Bovine serum albumin (BSA) was loaded into the fiber core. The greater the volume of the protein-free aqueous phase dispersed into the polymeric continuous phase emulsion, the greater the total release of BSA encapsulated by a core gel comprised of 1% sodium alginate solution.; Modifications to the gel and fiber compositions enabled us to deliver, over a period of 25 days, biologically active nerve growth factor (NGF) from this core-sheath format into serum-free media supplemented with BSA. The biological activity of the NGF was quantitatively verified through a PC12 cell-based survivability assay using the agent alamarBlue(TM). Additional qualitative verification of the NGF bioactivity occurred through exposure of PC12 cells in culture to supernatants from the release studies and to co-cultured fibers. ELISA verified detectable concentrations of NGF in solution throughout a period of 30 days.; We conclude this fiber format provides a promising vehicle for in vivo delivery of biologically sensitive molecules. Its biocompatibility and biodegradability also allow for its use as a possible substrate for tissue engineering applications.
机译:我们已经开发了一种新型的可生物降解的聚合物纤维结构,该结构可通过湿纺工艺与多糖预水凝胶溶液作为芯液共挤出为芯鞘型式。凝胶和聚合物的性质可以进行广泛的修饰,从而产生了多种纤维形态,从而为释放负载的蛋白质,生长因子,药物和其他治疗剂提供了多种特性。通过将它们掺入水凝胶中,将它们作为分散相掺入挤出成纤维外皮的聚合物连续相乳液中或通过其组合,可以保护这些生物敏感剂免于变性。多种药物可以这种方式共同加载,从而产生多种生物学活性的治疗能力。我们表明这种核心鞘纤维格式将加载模型蛋白,可以在体外延长时间交付。将可生物降解的生物相容性纤维从聚合物乳液中挤出,该聚合物乳液包括溶解于氯仿中的各种分子量的聚(L-乳酸)(PLLA)溶液,并含有分散的无蛋白水相,占乳剂体积的10%。牛血清白蛋白(BSA)被加载到纤维核心。分散在聚合物连续相乳液中的无蛋白水相的体积越大,被1%海藻酸钠溶液组成的核心凝胶所包封的BSA的总释放量越大。凝胶和纤维成分的修饰使我们能够在25天的时间内将这种核心鞘形式的生物活性神经生长因子(NGF)输送到补充了BSA的无血清培养基中。使用试剂alamarBlueTM通过基于PC12细胞的生存能力测定法定量验证了NGF的生物学活性。通过将培养物中的PC12细胞暴露于释放研究的上清液和共培养的纤维,可以对NGF的生物活性进行其他定性验证。 ELISA验证了在30天内可检测到的NGF浓度。我们得出结论,这种纤维形式为体内递送生物敏感分子提供了一种有希望的载体。其生物相容性和生物降解性也使其可用作组织工程应用的可能基质。

著录项

  • 作者

    Crow, Brent Benjamin.;

  • 作者单位

    The University of Texas at Arlington.;

  • 授予单位 The University of Texas at Arlington.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 169 p.
  • 总页数 169
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

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