Development of NanoBiomaterials for 3D/4D Bioprinting

全世界有数百万人在等待器官移植。即使是幸运地接受器官移植的人也有严重并发症的风险。几十年来，研究人员一直在试图开发替代解决方案。我们的梦想是，移植器官、器官贴片，甚至完全替代的器官都可以用患者自己的细胞来制造。3D生物打印是添加剂制造的一个新兴分支，它可能会让这个梦想成为现实。此外，使用人源细胞的3D生物打印组织模型可以使药物测试比动物测试更快、更便宜，并且与人类具有更好的生物学相关性，从而减少开发救命药物的时间和成本。3D生物打印的潜在社会和经济影响是巨大的。3D生物打印使用生物材料和细胞作为“生物墨水”来打印3D组织状结构。在过去的几年里，生物墨水材料、印刷工具和方法的研究迅速增长。然而，重大的技术障碍依然存在。这项拟议的研究计划旨在利用我们在化学和纳米材料方面的专业知识和经验来开发新型生物墨水材料。这种新型生物墨水是为一种名为微挤压的3D生物打印方法设计的，这是一种常用的方法，通过喷嘴分配粘性生物墨水来构建结构。虽然挤压法适合于高单元密度的打印，但对于精密打印来说并不理想，打印过程中施加的高压可能会对单元产生不利影响。为了解决这些限制并实现微挤压打印的全部潜力，我们提出了碳基纳米材料、聚合物及其化学衍生物的复合材料和强大的交联策略，使打印能够在细胞分辨率下进行，打印速度比最先进的打印速度高2个数量级。我们将通过3D打印人体血管和包裹神经细胞的凝胶来展示生物墨水的“可打印性”。总而言之，我们的研究将丰富高通量3D生物打印的油墨材料库，填补3D生物打印在生物制造和推进翻译研究方面的重大空白。所获得的知识也将极大地有助于未来的材料发展，并引起化学家和材料科学家的兴趣。拟议的计划使我们能够继续培训和留住加拿大最聪明的人才，以及吸引外国人才。申请的赠款将在资助期间的任何时候支持三名受训人员，以获得全面的研究技能。拟议研究的多学科性质将为学员提供一个围绕基础科学和应用科学工作的独特机会，培养下一代全面发展的科学家。我们的目标也是培养高素质的人才，他们将为加拿大卓越的科学做出贡献，并为加拿大快速增长的生物制造行业提供高技能工人。

Millions of people are on the waiting list for organ transplantation worldwide. Even people fortunate to receive organ transplants risk severe complications. For decades, researchers have been trying to develop alternative solutions. It is our dream that grafts, organ patches, and even full replacement organs can be fabricated using a patient's own cells. 3D bioprinting, an emerging branch of additive manufacturing, may make this dream come true. Furthermore, 3D bioprinted tissue models using human-derived cells can make drug testing faster, cheaper, and with better biological relevance to humans than animal testing, reducing the time and cost of developing life-saving medicine. The potential social and economic impacts of 3D bioprinting are enormous. 3D bioprinting uses biomaterials and cells as "bioink" to print 3D tissue-like structures. The past few years saw a rapid rise in research on bioink materials, printing tools and methods. However, significant technological hurdles remain. This proposed research program aims to leverage our expertise and experience in chemistry and nanomaterial to develop novel bioink materials. The novel bioink is designed for a 3D bioprinting method called microextrusion, a commonly used method that builds structure by dispensing viscous bioink through a nozzle. Although suited for printing with high cell density, the extrusion method is not ideal for precision printing and the high pressure applied during printing can adversely affect cells. To address the limitations and realize the full potential of microextrusion printing, we propose composites of carbon-based nanomaterials, polymers, and their chemical derivatives and a robust cross-linking strategy, enabling printing in cellular resolution and with a print speed 2 orders higher than the state-of-the-art. We will showcase the "printability" of the bioink by 3D printing of human blood vessels and gels encapsulating nerve cells. In the grand scheme of things, our research will enrich the library of ink materials for high-throughput 3D bioprinting, filling a major gap in biomanufacturing and thrusting translational research on 3D bioprinting. The knowledge gained will also greatly benefit future material development and be of interest to chemists and material scientists. The proposed program enable us to continue in training and retaining Canada's brightest minds, as well as attracting foreign talents. The requested grant will support three trainees at any point during the funding period to gain comprehensive research skills. The multidisciplinary nature of the proposed research will provide trainees with a unique opportunity in work revolving fundamental and applied science, nurturing for the next-generation well-rounded scientists. It is also our goal to train highly qualified personnel who will contribute to the Canadian scientific excellence and supply highly skilled workers for the fast-growing biomanufacturing industry in Canada.