EAGER: A Hybrid Nano-Bioprinting System for Tissue Engineering

这一早期概念探索性研究资助(AGIRE)的研究目标是了解纳米生物打印如何影响细胞存活和功能。我们将探讨两个参数的影响。1.纳米颗粒的大小和组成；以及2.纳米颗粒相对于细胞的位置。通过这些目标，将促进对生物打印过程中细胞-纳米颗粒相互作用的基本理解。这将导致对纳米生物打印的深入研究，并更接近于实现用于移植和药物发现的纳米功能化组织工程结构的大规模生产。这项研究的学术价值在于发现了纳米制造过程中纳米颗粒与微米级细胞的相互作用，以及这种相互作用如何转化为生物学结果。通过了解基本机制，纳米粒子的制造和使用可以将细胞影响降至最低。最重要的是，这些研究将使具有集成纳米结构的微观和宏观规模的健壮、可行的组织工程构建得以放大。对这些结构中的细胞和生物活性因子的动态操纵和跟踪具有改变组织工程学的潜力。该研究项目的更广泛的影响在于其潜在的增强纳米颗粒生化和生物力学效应的知识，特别是纳米颗粒和细胞如何在生物打印系统中相互作用的知识。这在医学的纳米制造中有着广泛的应用，因为当用于成像或癌症治疗时，纳米颗粒与机械敏感组织(血管、骨骼、肺)相互作用。纳米粒子参数的发现将纳米粒子和细胞力学之间的负面作用降至最低，这可能会创造出更安全、更有效的纳米治疗方法。该项目教育计划的更广泛影响是向机械工程师展示纳米技术如何应用于改善医疗保健，以及在社会背景下通过尖端技术激励未来的工程师。

The research objective of this EArly-Concept Grant for Exploratory Research (EAGER) is to understand how nanobioprinting affects cell viability and function. The effect of two parameters will be explored. 1. Nanoparticle size and composition; and 2. Nanoparticle location relative to the cell. Through these objectives, the fundamental understanding of cell-nanoparticle interactions in the bioprinting process will be advanced. This will lead towards advanced studies of nanobioprinting and closer to realizing large scale production of nano-functionalized tissue engineering structures for transplantation and drug discovery. The intellectual merit of this research lies in discovery of nanoparticle interaction with micron-scale cells in nanomanufacturing processes, and how this interaction translates into biological outcomes. By understanding fundamental mechanisms, nanoparticles can be manufactured and used in ways which minimize cellular effects. Most importantly, these studies will enable scale-up of micro- and macro-scale robust, viable tissue engineering constructs with integrated nanostructures. The dynamic manipulation and tracking of cells and bioactive factors within these structures has potential to transform tissue engineering.The broader impact of the research project is in its potential to enhance knowledge of nanoparticle biochemical and biomechanical effects, in particular how nanoparticles and cell interact in the bioprinting system. This has a wide reach in nanomanufacturing for medicine, since nanoparticles interact with mechanosensitive tissues (vasculature, bones, lungs) when used for imaging or cancer treatment. Discovery of nanoparticle parameters that minimize negative interaction between nanoparticles and cell mechanics could create safer, more effective nanotherapy. The broader impacts of the project's educational program are to show mechanical engineers how nanotechnology can be applied to improve healthcare, as well as to inspire future engineers through cutting edge technology in a social context.