Hybrid 3D bioprinting systems for fabricating heterogeneous, vascularized tissue constructs

虽然传统的2D打印机在平面上打印，但3D打印机允许在垂直方向上添加另一个维度，以逐层方式构建完整的3D对象。与这个过程类似，生物打印寻求沉积一层又一层的生物材料来构建3D身体部位。从移植接受者那里获取干细胞并打印出来建立一个替代器官，可以帮助解决目前器官移植的问题，如等待时间长和免疫排斥。然而，现有的3D生物打印技术在打印具有血管的不同组织和器官时是有限的，血管对于向构成这些结构的细胞供应氧气和营养是必不可少的。这项研究项目旨在开发一种3D生物打印系统，该系统能够打印具有血管网络的物理上不同的组织结构，更像自然组织。制造这种组织的需求为长期的研究目标奠定了基础，即开发和优化先进的3D生物打印系统，以复制自然组织的复杂结构，并最终实现整个器官的打印。为了实现这一长期目标，该计划的具体短期目标包括：(I)研究一种新型的灰度立体光固化三维生物打印方法，以制备物理上不均匀的组织支架；(Ii)研究一种基于激光二极管的挤压生物打印方法，以打印用于血管再生的中空纤维支架；以及(Iii)开发一种通过集成立体光固化和挤压三维生物打印功能来制造异质、血管组织构建物的方法。这项研究计划将通过打印越来越逼真的复杂组织结构，为先进的生物制造领域做出重要贡献。利用新型混合3D生物打印系统的独特优势，拟议的研究将产生创新的3D生物打印技术、组织支架的新方法和设计指南，以及首个适合实际应用的3D生物打印系统。这些智能、混合生物打印平台将立即应用于再生医学和药物研发领域，从而使加拿大社会的健康和经济受益。该研究计划将在为患有各种疾病的加拿大人提供治疗方面创造新的技术选择，还将通过初创公司和向加拿大公司转让技术来创造新的就业机会。此外，该计划还将为HQP提供跨学科培训，使他们掌握所需的学术和专业技能，以便在先进的生物制造和医疗保健技术方面产生长期影响和新举措。

While traditional 2D printers print on a flat surface, 3D printers enable the addition of another dimension in the vertical direction to build a complete 3D object in a layer-by-layer fashion. Analogous to this process, bioprinting seeks to deposit layers of biomaterials to build 3D body parts. Harvesting stem cells from a transplant recipient and printing them to build a replacement organ could help solve current organ transplantation problems such as long wait times and the immune rejection. However, existing 3D bioprinting technology is limited when it comes to printing heterogeneous tissues and organs with blood vessels, which are essential for the supply of oxygen and nutrients to cells that are constituent of these structures. This research project aims to develop a 3D bioprinting system that is capable of printing physically heterogeneous tissue structures with blood vessel networks, that are more reminiscent of natural tissues. The demand for fabricating such tissues has set the basis for the long-term research goal, which is to develop and optimize advanced 3D bioprinting systems to replicate the complex structures of natural tissues and to eventually realize the printing of whole organs. To accomplish this long-term goal, specific short-term objectives of this program include: (i) The investigation of a novel grayscale stereolithographic 3D bioprinting method to fabricate physically heterogeneous tissue scaffolds; (ii) The investigation of a laser diode-based extrusion bioprinting method to print hollow fibrous scaffolds for blood vessel regeneration; and (iii) The development of a method to fabricate heterogeneous, vascularized tissue constructs by integrating the stereolithographic and extrusion 3D bioprinting functionalities. This research program will make important contributions to the field of advanced biomanufacturing by enabling the printing of increasingly realistic complex tissue structures. Utilizing the unique advantages of the novel hybrid 3D bioprinting system, the proposed research will result in the creation of innovative 3D bioprinting technologies, new methods and design guidelines for tissue scaffolds, and first-of-their-kinds 3D bioprinting systems suitable for practical application. These intelligent, hybrid bioprinting platforms will find immediate application in the fields of regenerative medicine and drug discovery, thus benefiting both the health and economy of Canadian society. The research program will create new technological options in providing therapeutic treatments to Canadians suffering from various diseases and will also spark the creation of new jobs through start-up companies and technology transfer to Canadian companies. Moreover, this program will also provide interdisciplinary training to HQPs and make them equip them with required academic and professional skills for a long-term impact and new initiatives in advanced biomanufacturing and healthcare technologies.