Biofunctional fibers by polyelectrolyte complexation

描述（由申请人提供）：纤维形式的生物材料可用于外科缝合线，编织医疗器械，如血管移植物和组织工程支架等。纤维支架由于其固有的优点，包括细胞附着的高表面积和可控制的多孔结构，在组织工程中很有吸引力。传统的纤维制造工艺需要加热或变性溶剂。因此，在这些纤维支架中掺入生物材料是有限的或困难的。我们提出利用多元电解质络合技术制备具有包封生长因子和表面固定化配体生物功能的纤维。界面聚电解质络合是两个带相反电荷的聚电解质聚集在一起时发生的自组装过程。在水溶液中进行，这个过程是温和的，足以将蛋白质包封或固定到纤维中。这种纤维对于组织工程的应用特别有吸引力，因为最佳的组织工程需要的不仅仅是一种惰性支架，而不仅仅是作为细胞附着和细胞生长的基质。粘附分子、生长和分化因子、甚至质粒DNA等形式的线索或信号分子应以空间确定的方式纳入这些支架中，以协调新组织的生长。我们建议通过评估聚合物组成、反电荷聚电解质浓度、温度、电荷密度和纤维拉伸速率等关键参数来了解纤维形成的机理。以水溶性几丁质或壳聚糖为聚阳离子，海藻酸盐或肝素为聚阴离子合成纤维。通过测定这些纤维的物理、化学和生物特性，建立这些纤维的结构性能关系。我们将通过包裹药物、蛋白质、DNA纳米颗粒，以及用链亲和素修饰纤维表面，使生物素化配体能够附着在纤维中，从而将生物功能引入纤维。最后，我们将评估在这些生物功能纤维的非织造网上培养的原代肝细胞的细胞行为。预计本研究成果将产生具有生物医学应用价值的新型生物功能纤维生物材料。

DESCRIPTION (provided by applicant): Biomaterials in the form of fibers find applications in surgical sutures, woven medical devices such as vascular grafts, and tissue engineering scaffolds, among others. Fibrous scaffolds are attractive in tissue engineering for their inherent advantages, including high surface area for cell attachment and controlled porous architecture. Conventional fiber fabrication procedures require heat or denaturing solvents. Incorporation of biological materials in these fibrous scaffolds have therefore been limited or difficult. We propose to use the interracial polyelectrolyte complexation technique to fabricate fibers that can possess biofunctionalities of encapsulated growth factors and surface-immobilized ligands. Interfacial polyelectrolyte complexation is a process of self-assembly that occurs when two oppositely charged polyelectrolytes come together. Taking place in aqueous solutions, the process is mild enough for encapsulation or immobilization of proteins into the fibers. Such fibers would be particularly attractive for tissue engineering applications, where optimal tissue engineering requires more than an inert scaffold to serve merely as a substrate for cell attachment and cell growth. Cues or signal molecules in the form of adhesion molecules, growth and differentiation factors, or even plasmid DNA, should be incorporated into these scaffolds in a spatially defined manner to orchestrate the growth of new tissue. We propose to understand the mechanism of fiber formation by evaluating the critical parameters of polymer composition, concentration of the oppositely charged polyelectrolytes, temperature, charge density, and fiber draw rate. Fibers will be synthesized based on water-soluble chitin or chitosan as the polycation, and alginate or heparin as the polyanion. The structure property relationship of these fibers will be established by determining their physical, chemical, and biology properties. We will introduce biofunctionalities into the fibers by encapsulating drugs, proteins, DNA nanoparticles, as well as decorating the fiber surface with streptavidin to allow attachment of biotinylated ligands. Finally we will evaluate the cell behavior of primary hepatocytes cultured on a non-woven mesh of these biofunctional fibers. It is expected that findings in this proposal will produce novel biofunctional fibrous biomaterials with interesting biomedical applications.