Engineering granular and metamaterial structures from biodegradable and biocompatible polyester elastomers

颗粒和超材料结构已经彻底改变了小型化设备和微驱动的发展，但它们在组织和器官芯片工程中的应用是有限的。在之前的DG周期中，使用uv交联弹性体的3D冲压，我的团队创建了复杂的结构，如AngioChip，可注射组织和跳动的心脏心室。然而，它们的组装需要多个光刻步骤，而且是一个繁琐的一层一层的过程，需要相当多的手工技能。我假设，新一代生物相容性弹性体的颗粒和超材料结构工程将解决材料多功能性和可扩展处理的问题，同时提供新的功能，如材料特性图案和孔隙率控制，这些都是目前使用散装弹性体方法无法实现的。在项目1中，我们将为一系列组织工程和器官芯片应用合成新的生物相容性弹性体。将测试预聚物的流变性、交联时间和力学性能。使用微流体，我们将从新的弹性体中创建单分散的油墨颗粒，并使用部分UV固化来稳定它们。我们将探索从墨水颗粒中控制生物分子的释放，用导电结构域使它们功能化，并测试触发愈合特性。在项目2中，我们将通过使用堵塞弹性体颗粒墨水3D打印管状和超材料结构来推进支架技术。与3D打印的散装弹性体相比，我们希望实现对新管状结构蛋白质的高渗透性。通过在不同的空间位置组合不同性质的墨水颗粒，将在管内产生性质的梯度。我们将3D打印一个可渗透且稳定的血管腔，用于血管生成因子和外泌体的灌注和释放。虽然细胞包裹的水凝胶可以以高分辨率3D打印，但它们的结构会随着细胞重塑基质而变形。聚合物更稳定，但它们本质上是不可渗透的。我们将通过将细胞和水凝胶与弹性墨水颗粒一起共打印来解决这个问题，以提高结构稳定性并将细胞嵌入血管壁。锥形超材料支架将通过使用新型弹性体墨水的3D打印辅助周期性晶格来创建，以创建一个灵活的结构，可以独特地支持心室收缩。所描述的方法将使我们能够将结构生产的吞吐量提高34,560倍，取代缓慢的3D冲压，制造一个1.5厘米长的管状导管需要72小时，而可扩展的3D打印只需要7.2秒。项目1和项目2是相互关联的，因为项目1中的聚合物和弹性体油墨颗粒将在项目2中用于构建复杂的颗粒和超材料结构。拟培养博士生3人，硕士生2人，本科生5人。

Granular and metamaterial structures have revolutionized the development of miniaturized devices and microactuation, yet their use in tissue and organ-on-a-chip engineering is limited. In the previous DG cycle, using 3D stamping of UV-crosslinkable elastomers my group created complex structures such as AngioChip, injectable tissues and beating heart ventricles. However, their assembly required multiple photolithography steps, and a tedious layer-by-layer process requiring considerable manual skill. I hypothesize that engineering of granular and metamaterial structures from a new generation of biocompatible elastomers will solve the issue of material versatility and scalable processing, while providing new capabilities, such as material property patterning and porosity control, that are not realized using current bulk elastomeric approaches. In Project 1, we will synthesize new biocompatible elastomers for a range of tissue engineering and organ-on-a-chip applications. Prepolymer rheology, crosslinking time and mechanical properties will be tested. Using microfluidics, we will create monodisperse ink particles from the new elastomers, and stabilize them using partial UV curing. We will explore controlled release of biomolecules from the ink particles, functionalize them with conductive domains and test triggered-healing properties. In Project 2, we will advance scaffold technologies through 3D printing of tubular and metamaterial structures using jammed elastomer particle inks. We expect to achieve a significantly higher permeability to proteins of the new tubular structures compared to those 3D printed from bulk elastomers. Gradients of properties within the tubes will be created by combining ink particles of various properties in distinct spatial locations. We will 3D print a permeable yet stable vascular lumen for perfusion and release of angiogenic factors and exosomes. While cell laiden hydrogels can be 3D printed with high resolution, their structure deforms as cells remodel the matrix. Polymers are more stable, but they are inherently non-permeable. We will solve this problem by co-printing cells and hydrogels together with elastomeric ink particles to improve structure stability and embed the cells into the vessel wall. Conical metamaterial  scaffolds will be created by 3D printing auxetic periodic lattice using new elastomer inks, to create a flexible structure that can uniquely support ventricle contraction. The described approach will enable us to increase throughput of structure production by 34,560 fold replacing a slow 3D stamping, requiring 72 hr for fabrication of one 1.5cm long tubular conduit, by a scalable 3D printing that requires only 7.2s. Project 1 and 2 are interconnected as polymers and elastomeric ink particles form Project 1, will be used to construct complex granular and metamaterial structures in Project 2. Three PhD, 2 MASc and 5 undergraduate students will be trained through the proposed studies.