Wrinkled non-spherical microparticles as a new microcarrier for cell culture applications in Sanofi Pasteur

用于在生物反应器中生产各种疫苗的哺乳动物细胞通常生长在称为微载体的支撑基质上，微载体可以由许多不同的材料制成，包括deae -葡聚糖、玻璃、聚苯乙烯塑料、丙烯酰胺、胶原蛋白和海藻酸盐。商业微载体只有光滑表面的球形。球体具有最小的表面积体积比，因此对于给定的体积，细胞可附着的表面空间最小。除了它们的球形外，可用的微载体表面光滑，使得增加表面积以提高细胞培养能力变得困难。当前基于微载体的细胞培养的另一个挑战是，在细胞附着和分离（恢复）之前，需要对微载体表面进行化学修饰-通常涉及昂贵的酶。瑞尔森大学的Hwang小组已经开发出一种技术，可以生产具有设计形状和可调节表面皱纹的微载体，从而显着增加其表面积。当用于细胞培养时，这些微载体可以大大提高细胞的附着能力。此外，微载体表面没有化学修饰，这简化了细胞附着和回收过程，而无需使用酶。赛诺菲巴斯德是世界领先的疫苗制造公司，其总部位于多伦多，拥有加拿大最大的疫苗研发设施。赛诺菲利用微载体通过哺乳动物细胞培养生产几种疫苗。这项资助将使赛诺菲和瑞尔森团队能够开始努力将这些基于非球形微载体的技术成功地整合到他们的疫苗生产中。因此，未来赛诺菲的细胞培养效率和疫苗产量可以显著提高。

Mammalian cells used to produce various vaccines in bioreactors are typically grown on a support matrixtermed a microcarrier, which can be made of a number of different materials including DEAE-dextran, glass,polystyrene plastic, acrylamide, collagen, and alginate. Commercial microcarriers are only available in smoothsurface, spherical forms. Spheres have the smallest surface-area-to-volume ratio, and therefore the least surfacespace available for cells to attach for a given volume. In addition to their spherical shape, the smooth surface ofavailable microcarriers makes it difficult to increase the surface area for cell culture capacity improvement.Another challenge in current microcarrier-based cell culture is that the microcarrier surface needs to bechemically modified prior to cell attachment and detachment (recovery) - often involving expensive enzymes.The Hwang group at Ryerson has developed a technique that can produce microcarriers with designed shapesand tuneable surface wrinkles that can significantly increase their surface area. When used for cell culture,these microcarriers can greatly improve cell attaching capacity. In addition, the microcarrier surface is notchemically modified, which simplifies the cell attaching and recovery process without using enzymes.Sanofi Pasteur is a world leading vaccine manufacturing company, and its head office in Toronto has Canada'slargest vaccine R&D facility. Sanofi manufactures several vaccines through mammalian cell culture usingmicrocarriers. This Engage grant will enable Sanofi and the Ryerson team to begin working towardssuccessfully integrating these non-spherical-microcarrier-based technologies into their vaccine production. As aresult, cell culture efficiency and vaccine production at Sanofi can be significantly improved in the future.