Smart scaffolds for guided tissue and organ assembly

用于引导组织和器官组装的智能支架

• 批准号: RGPIN-2018-05500
• 负责人: Zhang, Boyang
• 金额: $ 2.77万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=669648
• 关键词: Smart; scaffolds; guided; tissue; organ

Reproducing the complexity of human organs is daunting and demands new tissue assembly strategy that does not simply view a scaffold as a static skeleton that provides structural support, but a dynamic machine that guides tissue assembly over time. The objective of this Discovery research is to develop smart scaffolds that can structurally transform and automatically assemble to guide dynamic tissue growth on multiple lengths and timescales. Specific research projects will focus on two main themes, each target a particular challenge in biofabrication. Yet the two approaches complement each other and can be integrated.******Foldable vascular scaffolds. Tissue vascularization is the most significant obstacle in tissue engineering and has received tremendous attention in biofabrication. We recently developed a photolithographic 3D stamping technique to create a polymer scaffold, termed AngioChip, with a generic and permeable vascular network made from an elastic biodegradable polymer. Despite the high potential of this approach, we have only fabricated scaffolds up to 2 mm in thickness. To circumvent the need to tediously print or microfabricate complex structures in 3D, we aim to develop a foldable AngioChip vessel that can be folded and re-shaped from a 2D pattern into an intricate 3D vascular structure. We will establish basic design rules that guide the folding of the AngioChip vessel based on both material mechanical properties as well as physical constraints of the bioreactor. ******Magnetic micro-scaffolds that self-assemble. Many organs (heart, liver, etc.) are made from repeating functional tissue units. Recognizing this characteristic, we aim to explore new approaches that automatically assemble micro-tissue modules in vitro with minimal intervention. Specifically, we will incorporate nanoscale magnetic particles within microscale scaffolds to control both microscopic cell alignment and macroscopic tissue orientation during assembly. This strategy will guide dynamic tissue growth over multiple lengths and timescales. To validate this approach, both cardiac cells and liver cells will be used as these two organs exhibit distinct tissue architectures. ******The first project will enable us to build large-scale vascular networks while the second project will allow us to control the architecture of parenchymal tissues. When integrated together, these smart scaffolds will establish unprecedented control over the high-level organization of complex solid tissues. Successful development of transplantable tissue substitute will fundamentally change the way we treat disease and repair damaged tissues. This discovery program is designed to overcome the fundamental challenges in biofabrication and will have a broad impact on the medical treatment of a wide range of organ systems. Our interdisciplinary research program will also benefit HQP training in emerging areas of biotechnology.

复制人体器官的复杂性是令人生畏的，需要新的组织组装策略，不能简单地将支架视为提供结构支撑的静态骨架，而是随着时间的推移引导组织组装的动态机器。这项发现研究的目标是开发智能支架，可以在结构上转换和自动组装，以指导多个长度和时间尺度上的动态组织生长。具体的研究项目将侧重于两个主题，每个主题都针对生物制造业的一个特定挑战。然而，这两种方法是相辅相成的，可以结合起来。可折叠血管支架。组织血管化是组织工程的最大障碍，也是生物制品领域的研究热点。我们最近开发了一种3D打印技术来创建一种聚合物支架，称为AngioChip，具有由弹性可生物降解聚合物制成的通用和可渗透的血管网络。尽管这种方法具有很高的潜力，但我们只制造了厚度达2 mm的支架。为了避免在3D中繁琐地打印或微制造复杂结构的需要，我们的目标是开发一种可折叠的血管芯片血管，该血管可以从2D模式折叠和重新成形为复杂的3D血管结构。我们将建立基本的设计规则，根据材料的机械性能以及生物反应器的物理约束来指导AngioChip血管的折叠。** 自我组装的磁性微支架。许多器官（心脏、肝脏等）是由重复的功能组织单元组成的。认识到这一特点，我们的目标是探索新的方法，自动组装微组织模块在体外以最小的干预。具体来说，我们将把纳米级的磁性颗粒在微米级的支架，以控制组装过程中微观细胞的排列和宏观组织的方向。该策略将在多个长度和时间尺度上指导动态组织生长。为了验证这种方法，将使用心脏细胞和肝细胞，因为这两种器官表现出不同的组织结构。** 第一个项目将使我们能够建立大规模的血管网络，而第二个项目将使我们能够控制实质组织的结构。当整合在一起时，这些智能支架将对复杂实体组织的高层次组织建立前所未有的控制。可移植组织替代物的成功开发将从根本上改变我们治疗疾病和修复受损组织的方式。这项发现计划旨在克服生物制造业的根本挑战，并将对广泛的器官系统的医疗产生广泛的影响。我们的跨学科研究计划也将有利于生物技术新兴领域的HQP培训。