Engineering granular and metamaterial structures from biodegradable and biocompatible polyester elastomers

采用可生物降解和生物相容性聚酯弹性体设计颗粒和超材料结构

• 批准号: RGPIN-2022-04164
• 负责人: Radisic, Milica
• 金额: $ 6.56万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746050
• 关键词: Engineering; granular; metamaterial; structures; biodegradable

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.

颗粒和超材料结构彻底改变了微型化设备和微驱动的发展，但它们在组织和芯片上器官工程中的应用有限。在之前的DG周期中，我的团队使用可紫外线交联弹性体的3D冲压创建了复杂的结构，如血管芯片、可注射组织和跳动的心脏。然而，它们的组装需要多个光刻步骤，以及繁琐的逐层工艺，需要相当多的手工技能。我假设，从新一代生物兼容弹性体中设计颗粒和超材料结构将解决材料的通用性和可伸缩加工的问题，同时提供目前的本体弹性体方法无法实现的新功能，如材料特性图案化和孔隙率控制。在项目1中，我们将为一系列组织工程和芯片上器官应用合成新的生物兼容弹性体。将对预聚体的流变性、交联时间和机械性能进行测试。使用微流体，我们将从新的弹性体中创建单分散油墨颗粒，并使用部分UV固化来稳定它们。我们将探索生物分子从墨水颗粒中的受控释放，使用导电域对其进行功能化，并测试触发愈合性能。在项目2中，我们将通过使用堵塞的弹性体颗粒墨水对管状和超材料结构进行3D打印来推进脚手架技术。我们预计，与由主体弹性体打印的3D打印相比，新的管状结构对蛋白质的渗透性要高得多。管内的特性梯度将通过在不同的空间位置组合各种特性的墨水颗粒来创建。我们将3D打印一个可渗透但稳定的血管管腔，用于血管生成因子和外切体的灌流和释放。虽然细胞层水凝胶可以以高分辨率进行3D打印，但它们的结构会随着细胞对基质的重塑而变形。聚合物更稳定，但它们本质上是不透水的。我们将通过将细胞和水凝胶与弹性墨水颗粒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3D打印拉伸周期点阵使用新的弹性体墨水创建，以创建一种灵活的结构，可以独特地支持脑室收缩。所描述的方法将使我们能够将结构生产的产量提高34,560倍，通过只需要7.2秒的可扩展3D打印来取代缓慢的3D冲压，制造一个1.5厘米长的管状管道需要72小时。项目1和项目2作为聚合物和弹性体墨水颗粒相互连接，将在项目2中用于构建复杂的颗粒和超材料结构。通过拟议的研究，将培养3名博士、2名硕士和5名本科生。