Smart scaffolds for guided tissue and organ assembly

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，而不是简单地将支架视为提供结构支持的静态骨架，而是一个引导组织组装的动态机器。Discovery研究的目标是开发智能支架，这种支架可以在多种长度和时间尺度上进行结构转换和自动组装，以指导动态组织生长。具体的研究项目将集中在两个主要主题上，每个主题都针对生物制造中的一个特定挑战。然而，这两种方法相辅相成，可以整合。******可折叠血管支架。组织血管化是组织工程中最重要的障碍，在生物制造领域受到了极大的关注。我们最近开发了一种光刻3D冲压技术，用于制造一种聚合物支架，称为AngioChip，它具有由弹性可生物降解聚合物制成的通用且可渗透的血管网络。尽管这种方法潜力巨大，但我们只制造了厚度达2毫米的支架。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AngioChip血管，可以从2D模式折叠和重新塑造成复杂的3D血管结构。我们将根据材料的机械性能和生物反应器的物理约束，建立指导AngioChip血管折叠的基本设计规则。******自组装的磁性微支架。许多器官（心脏、肝脏等）都是由重复的功能组织单元构成的。认识到这一特点，我们的目标是探索在体外以最小干预自动组装微组织模块的新方法。具体来说，我们将在微尺度支架中加入纳米级磁性颗粒，以在组装过程中控制微观细胞排列和宏观组织方向。该策略将引导动态组织生长在多个长度和时间尺度。为了验证这种方法，将使用心脏细胞和肝细胞，因为这两个器官具有不同的组织结构。******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。当集成在一起时，这些智能支架将对复杂实体组织的高级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中的基本挑战，并将对各种器官系统的医学治疗产生广泛的影响。我们的跨学科研究项目也将有利于生物技术新兴领域的HQP培训。

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.