Microfluidic Fiber Fabrication and its Application in Neural Tissue Engineering

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2016-01-01
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Sharifi, Farrokh
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Nastaran Hashemi
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Mechanical Engineering
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Abstract

Microfibers are becoming increasingly important for biomedical applications such as tissue engineering, drug delivery, and cell encapsulation. In this study, a microfluidic approach was used to fabricate biocompatible and biodegradable polymeric fibers. Chapter one gives an overview of the common microfiber fabrication methods followed by their advantages and disadvantages. Then, it focuses on the microfluidic platform and provides more information about different solidification strategies applied to fabricate fibers in this method. This chapter reviews some studies, which were recently published in this area as well.

Chapter two discusses using the microfluidic approach to fabricate continuous Polyvinyl alcohol (PVA) microfibers. It was shown that the size and cross-section of the PVA fibers can be controlled by changing the PVA concentration and flow rate ratio between the core and sheath fluids. The PVA concentration was varied from 6% to 12%, and the sheath-to-core flow rate ratio used for this study was in the range of 500:5 à µL/min to 500:20 à µL/min, respectively. The ribbon-shaped PVA fibers were fabricated using our microfluidic approach. Additionally, we simulated the microfluidic fiber fabrication process and the results consisted well with the experimental results. The dissolution and mechanical properties of the PVA fibers fabricated with different characteristics were also studied.

Chapter three focuses on fabricating polycaprolactone (PCL) microfibers using the microfluidic approach. It was shown that through variations of the sheath fluid flow rate and PCL concentration in the core solution, the morphology of the fibers and their cross sections can be tuned. The fibers were made using PCL concentrations of 2%, 5%, and 8% in the core fluid with a wide range of sheath-to-core flow rate ratios from 120:5 à µL/min to 10:5 à µL/min, respectively. The results revealed that the mechanical properties of the PCL fibers made using microfluidic approach were significantly improved compared to the PCL fibers made by other fiber fabrication methods. Additionally, the effects of flow rate ratio and PCL concentration on the mechanical properties of the PCL fibers were studied.

In chapter four, the PCL microfibers with different characteristics were used as fibrous scaffolds to get one step closer to the application of the polymeric fibers in tissue engineering. Adult Hippocampal Stem/Progenitor Cells (AHPCs) in vitro were chosen for this study. It was shown that the three-dimensional topography of the PCL substrates, along with chemical (extracellular matrix) guidance cues, supports the adhesion, survival, and differentiation of the AHPCs. Moreover, the PCL fibers with different sizes and shapes (straight and wavy) were used to quantitatively analyze cell adhesion, proliferation, and differentiation. Our first experiment showed that 5 μm had the most cell adhesion, 5 μm, straight 20 μm, and wavy 35 μm provided a significantly better condition for the glial differentiation compared to control. More cell proliferation was observed on the wavy 35 μm fibers than on straight 35 μm fibers, showing that fiber morphology may have an effect on cell proliferation. However, this study’s goals were to perform two more experiments in order to have more reliable results.

In chapter five, we used a microfluidic approach and photopolymerization strategy to fabricate PEGDA spherical particles as well as bow tie-shaped fibers. In this work, we showed that with immiscible and miscible fluids, spherical microparticles and bow tie shaped fibers can be fabricated using PEGDA. The flow rate ratio between the core and sheath fluids is found an important parameter to accurately tune the diameter of the particles as well as cross-section and size of the fibers. Glucose, sucrose, collagen, gelatin, PEG, and PVA were incorporated into the PEGDA fibers to study the porosity of the resulting fibers. It was found that sucrose and PVA can create porosity on the surface of the fibers after soaking the fibers in water for 6 days at 37 à °C. The tensile properties of the PEGDA fibers with different characteristics were tested. It was found that when the core flow rate increases, the resulting fibers become more stiff and brittle, which might be due to the increase of the cross-linking density. The mechanical properties of the PEGDA/collagen drop due to the low strength of the collagen, which is a natural polymer. On the other hand, the incorporation of glucose could improve the tensile properties of PEGDA fibers. In addition, we encapsulated the AHPCs into the PEGDA fibers in order to create a cell-laden fiber. Propidium Iodide (PI) was used for the cell viability, and the results showed that the cells could not survive. We believe that another hydrogel or the same polymer with higher molecular weight needs to be used in order to increase the cell survival into the hydrogel network.

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Fri Jan 01 00:00:00 UTC 2016