Microfluidics High-Resolution 3D-bioprinting for a Multidisciplinary Team

自70年代初以来，组织工程一直在研究，结果好坏参半。早期的研究受到缺乏创造新组织所需的创新生物相容性材料的限制。3D生物打印是一项相对较新的创新，它已经帮助克服了传统组织工程的局限性。3D生物打印为创造具有前所未有的细节、结构和仿生水平的组织和器官提供了可能性。 每种生物打印技术对生物墨水（一种含有生物材料混合物的溶液）都有不同的要求，可以对封装的细胞产生不同的效果。基于挤出的打印是最常用的技术，尽管它在所有技术中具有最低的细胞存活率。低存活率是由于印刷过程引起的剪切应力。它还提出了关于空间分辨率和其他参数的控制，如粘度，多细胞和多层印刷，以及定制设计复杂图案的能力有限的几个限制。 在这项提案中，我们要求一种基于新型微流体技术的高分辨率3D生物打印机系统，用于开发先进的生理相关组织模型。微流体生物打印技术不是通过针挤出而是通过所谓的同轴流聚焦来产生打印纤维，其中液体生物墨水流在微流体打印头中聚焦在交联剂流体流中。 这种方法保护细胞免受剪切应力的影响，同时允许精确控制生物墨水和构建体设计的几种性质。基于微流体的生物打印能够快速打印宏观尺度的3D组织结构，这些结构包含复杂的微观细节，以生成在结构和功能上精确的生物组织。所要求的设备将直接支持卡尔顿大学的三个多学科研究项目，并在一个独特的，包容性的和高度跨学科的科学网络中培训HQP。由于这种仪器的独特性和在学术环境中提供它的可能性，我们设想通过建立新的合作来快速扩展这个网络，这将使我们能够在战略上找到重要科学问题的答案，同时增强加拿大在组织工程新兴领域的创新和存在。

Tissue engineering has been researched since the early 70s with mixed results. Early studies were limited by the lack of innovative biocompatible materials needed to generate new tissue. 3D bioprinting is a relatively new innovation which is already helping to overcome the limitations of conventional tissue engineering. 3D-bioprinting has opened the possibility of creating tissues and organs with unprecedented level of details, structure and biomimicry. Each bioprinting technique has different requirements for the bio-ink (a solution containing a mixture of biomaterials) that can create diverse effects on the encapsulated cells. Extrusion-based printing is the most commonly adopted technique, although it has the lowest reported cell survival among all techniques. The low survival is due to the shear stress induced by the printing process. It also presents several limitations regarding the spatial resolution and control of other parameters such as viscosity, multicellular and multilayer printing, as well as limited capability of custom-design complex patterns. In this proposal we are requesting a high-resolution 3D bioprinter system based on novel microfluidics, for developing advanced physiologically relevant tissue models. Microfluidic bioprinting technology, generates the printed fibre not by extruding through a needle but through so-called coaxial flow focusing, in which a stream of a liquid bio-ink is focused in a stream of a crosslinker fluid in a microfluidic printheads. This approach protects cells from shear stress while allowing precise control of several properties of the bio-inks and constructs designs. Microfluidics-based bioprinting enables the rapid printing of macro-scale 3D tissue structures that incorporate intricate micro-level details to generate architecturally and functionally accurate biological tissues. The requested equipment will directly support three multidisciplinary research programs at Carleton University, and train HQP within a unique, inclusive, and highly interdisciplinary scientific network. Due to the uniqueness of such instrument and the possibility of having it available in an academic environment, we envision a quick expansion of this network by establishing new collaborations, which will position us strategically to find answers to important scientific questions while enhancing Canadian innovation and presence in the burgeoning field of tissue engineering.