Smart scaffolds for guided tissue and organ assembly

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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.