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.
Many diseases are caused by deterioration or loss of function of internal organs. Currently, these diseases are treated by transplanting an organ from another person. This solution is not ideal because there are not enough organs available and the body tends to reject these organs as foreign bodies. One solution is to build new organs through tissue engineering. However, most organs are quite in their structure. Therefore, advanced manufacturing techniques are needed to engineer new organs. We developed a system that allows us to print three-dimensional structures embedded with nanoparticles. These nanoparticles can be used to change the local chemical and mechanical properties of the structure, which would cause the cells within the engineered organ to have different function. The nanoparticles can also be used to track the health of cells within the organ non-invasively. Since the nanoparticles are also magnetic, we can move them within the structure after it is printed using a magnetic field. In this project, we determined how including these nanoparticles in the tissue manufacturing process impacts cell health and function. We investigated two different nanoparticle sizes (5 and 30 nm) and two different nanoparticle coatings (a sugar called dextran and a polymer called polyethylene glycol). We then determined how these nanoparticles affected the health and function of endothelial cells, which line all blood vessels. This cell type was selected since viable blood vessels are critical to supplying tissue engineered structures with oxygen and nutrients. Our results show that nanoparticles of all sizes and coating are readily taken up into the cell, after which they are segregated into cytoplasmic compartments. While bare iron oxide nanoparticles caused significant cell death at higher concentrations, nanoparticles that were coated with dextran or polyethylene glycol did not cause significant cell death. Dextran and polyethylene glycol coatings improved cell health by decreasing the amount of oxidative stress caused by having the iron oxide nanoparticles near or in the cells. The improvement in cell viability with nanoparticle coatings was also observed when cells and nanoparticles were printed within three-dimensional tissue-like structures. Our study shows that coated nanoparticles can be safely used in tissue engineering, and these new advanced manufacturing techniques may accelerate our ability to build new organs. We published a research paper on our results and incorporated lectures and laboratories on this topic into engineering courses.
