Tissue Engineering + Biofabrication Laboratory, Institute for Biomechanics , ETH Zürich , Otto-Stern-Weg 7 , 8093 Zürich , Switzerland.
Department of Biotechnology and Nanomedicine , SINTEF Industry , Richard Birkelands vei 3B , 7034 Trondheim , Norway.
ACS Appl Mater Interfaces. 2018 Nov 7;10(44):37820-37828. doi: 10.1021/acsami.8b13166. Epub 2018 Oct 26.
Three-dimensional (3D) bioprinting allows the fabrication of 3D structures containing living cells whose 3D shape and architecture are matched to a patient. The feature is desirable to achieve personalized treatment of trauma or diseases. However, realization of this promising technique in the clinic is greatly hindered by inferior mechanical properties of most biocompatible bioink materials. Here, we report a novel strategy to achieve printing large constructs with high printing quality and fidelity using an extrusion-based printer. We incorporate cationic nanoparticles in an anionic polymer mixture, which significantly improves mechanical properties, printability, and printing fidelity of the polymeric bioink due to electrostatic interactions between the nanoparticles and polymers. Addition of cationic-modified silica nanoparticles to an anionic polymer mixture composed of alginate and gellan gum results in significantly increased zero-shear viscosity (1062%) as well as storage modulus (486%). As a result, it is possible to print a large (centimeter-scale) porous structure with high printing quality, whereas the use of the polymeric ink without the nanoparticles leads to collapse of the printed structure during printing. We demonstrate such a mechanical enhancement is achieved by adding nanoparticles within a certain size range (<100 nm) and depends on concentration and surface chemistry of the nanoparticles as well as the length of polymers. Furthermore, shrinkage and swelling of the printed constructs during cross-linking are significantly suppressed by addition of nanoparticles compared with the ink without nanoparticles, which leads to high printing fidelity after cross-linking. The incorporated nanoparticles do not compromise biocompatibility of the polymeric ink, where high cell viability (>90%) and extracellular matrix secretion are observed for cells printed with nanocomposite inks. The design principle demonstrated can be applied for various anionic polymer-based systems, which could lead to achievement of 3D bioprinting-based personalized treatment.
三维（3D）生物打印允许制造包含活细胞的 3D 结构，这些细胞的 3D 形状和结构与患者相匹配。该功能是实现创伤或疾病个性化治疗的理想选择。然而，由于大多数生物相容性生物墨水材料的机械性能较差，该有前途的技术在临床上的实现受到了极大的阻碍。在这里，我们报告了一种使用基于挤出的打印机实现大体积结构高打印质量和保真度的新策略。我们将阳离子纳米粒子掺入阴离子聚合物混合物中，由于纳米粒子与聚合物之间的静电相互作用，这显著提高了聚合物生物墨水的机械性能、可打印性和打印保真度。在由藻酸盐和结冷胶组成的阴离子聚合物混合物中添加阳离子改性的硅纳米粒子，导致零剪切粘度（增加 1062%）和储能模量（增加 486%）显著增加。结果，可以打印具有高质量的大（厘米级）多孔结构，而在没有纳米粒子的情况下使用聚合物墨水会导致打印结构在打印过程中坍塌。我们证明，通过在一定尺寸范围内（<100nm）添加纳米粒子，可以实现这种机械增强，并且这种增强取决于纳米粒子的浓度和表面化学以及聚合物的长度。此外，与没有纳米粒子的墨水相比，添加纳米粒子可以显著抑制打印结构在交联过程中的收缩和膨胀，从而在交联后实现高打印保真度。掺入的纳米粒子不会损害聚合物墨水的生物相容性，用纳米复合材料墨水打印的细胞表现出>90%的高细胞活力和细胞外基质分泌。所展示的设计原则可应用于各种基于阴离子聚合物的系统，这可能导致基于 3D 生物打印的个性化治疗的实现。
