Smart scaffolds for guided tissue and organ assembly

复制人体器官的复杂性令人望而生畏，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。这项发现号研究的目标是开发能够进行结构转换和自动组装的智能支架，以引导组织在多个长度和时间尺度上动态生长。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方面的特定挑战。然而，这两种方法是相辅相成的，可以整合。 可折叠的血管支架。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冲压技术来创建一种名为AngioChip的聚合物支架，该支架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。尽管这种方法的潜力很大，但我们只制作了厚度不超过2毫米的支架。为了避免繁琐的3D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，它可以从2D图案折叠和重塑为复杂的3D血管结构。我们将建立基本的设计规则，指导血管芯片血管的折叠，既基于材料的机械性能，也基于生物反应器的物理约束。 可以自我组装的磁性微型支架。许多器官(心脏、肝脏等)是由重复的功能组织单元制成的。认识到这一特点，我们的目标是探索在体外以最少的干预自动组装微组织模块的新方法。具体地说，我们将在微尺度支架中加入纳米磁性颗粒，以控制组装过程中微观细胞的排列和宏观组织的取向。这一策略将引导组织在多个长度和时间尺度上的动态生长。为了验证这一方法，将同时使用心脏细胞和肝脏细胞，因为这两个器官显示出不同的组织结构。 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。当集成在一起时，这些智能支架将建立对复杂固体组织的高级组织的前所未有的控制。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。这一发现计划旨在克服生物制造中的根本挑战，并将对广泛器官系统的医疗产生广泛影响。我们的跨学科研究计划也将使新兴生物技术领域的HQP培训受益。

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.