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，研究人员一直在努力开发替代解决方案。这是我们的梦想，移植，器官补片，甚至完全替代器官可以用病人自己的细胞制造。3D生物打印，增材制造的一个新兴分支，可能会让这个梦想成为现实。此外，使用人源性细胞的3D生物打印组织模型可以使药物测试更快，更便宜，并且与动物测试相比与人类具有更好的生物相关性，从而减少开发救生药物的时间和成本。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组织样结构。在过去的几年里，生物墨水材料、打印工具和方法的研究迅速兴起。然而，仍然存在重大的技术障碍。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出的3D生物打印方法而设计的，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。虽然适用于高细胞密度的印刷，但挤出方法对于精密印刷并不理想，并且在印刷期间施加的高压会对细胞产生不利影响。为了解决这些局限性并实现微挤出打印的全部潜力，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，以及一种稳健的交联策略，能够以细胞分辨率进行打印，打印速度比最先进的技术高2个数量级。我们将展示“可打印性”通过3D打印人体血管和封装神经细胞的凝胶来实现生物墨水。在宏伟的计划中，我们的研究将丰富高通量3D生物打印的墨水材料库，填补生物制造的主要空白，并推动3D生物打印的转化研究。所获得的知识也将极大地有利于未来的材料开发，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，并吸引外国人才。申请的赠款将在资助期间的任何时候支持三名学员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独特的机会，在工作中旋转基础和应用科学，培养下一代全面的科学家。我们的目标也是培养高素质的人才，他们将为加拿大的科学成就做出贡献，并为加拿大快速发展的生物制造业提供高技能的工人。

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.