Department of Mechanical Engineering

Mr. Changxue Xu

Degree Candidacy: Doctor of Philosophy in Mechanical Engineering
Date: Tuesday, April 15, 2014
Time: 2:00 PM
Location: 132 EIB

Advisor: Dr. Richard Miller
Committee Members: Dr. Yong Huang, Dr. Rui Qiao, Dr. Xiangchun Xuan and Dr. Zhi Gao

Title: Inkjet Printing Of Three-Dimensional Vascular-Like Constructs From Cell Suspensions

ABSTRACT

Inkjet printing has found an increasing number of biofabrication applications, specifically organ printing, which has been emerging as a promising solution to the organ donor shortage. While some studies have been conducted to investigate various engineering problems associated with DOD inkjet printing of biological material-based fluids, the pinch-off, the droplet formation performance of cell-laden bioink, and the effects of electric field on droplet formation during piezoactuation-based DOD inkjet printing haven’t been systematically investigated. In addition, challenges in 3D vascular-like construct fabrication using DOD inkjet printing are to be identified and addressed accordingly. The objective of this study is to investigate the pinch-off during drop-on-demand (DOD) inkjet printing of viscoelastic biomaterials, the droplet formation performance during DOD inkjet printing of cell-laden bioink, the effects of electric field on droplet formation without forming a Taylor cone during piezoactuation-based DOD inkjet printing, and manufacturing challenges encountered during fabrication of 3D vascular-like constructs using DOD inkjet printing.

The pinch-off process during DOD inkjet printing of viscoelastic alginate solutions is systematically investigated by studying the effects of sodium alginate (NaAlg) concentration and operating conditions on the pinch-off behavior and location in this study. For the first time, it is found that there are four types of pinch-off which may exist during DOD inkjet printing of viscoelastic NaAlg solutions: front-pinching, exit-pinching, hybrid-pinching and middle-pinching, as classified based on the pinch-off location. In particular, front-pinching is governed by a balance of inertial and capillary stresses, while exit-pinching is governed by a balance of elastic and capillary stresses experienced by a forming jet. The apparent relaxation time, which is much smaller than the longest relaxation time, characterizes the ligament thinning process. Furthermore, an operating diagram is constructed with respect to the Weber number (We) and a proposed J number ( , where Oh is the Ohnesorge number and El is the elasticity number) to classify regimes for different types of pinch-off.

The droplet formation performance of cell-laden bioink is studied by investigating the effects of cell concentration on the breakup time, droplet size and velocity, and number of satellites. The droplet formation performance of comparable cell-laden and polystyrene bead-based suspensions is evaluated and further compared. It is found that the breakup time increases but the droplet size, droplet velocity, and number of satellites decrease as the cell concentration increases. Compared to the polystyrene bead-based suspension, the ejected fluid volume is less, the droplet velocity is smaller, and the breakup time is longer using the cell-laden bioink.

The electric field-assisted droplet formation under piezoactuation-based DOD inkjet printing is investigated. It is found that droplet velocity increases and the droplet size decreases with the increase of the applied voltage. Pinch-off locations may vary depending on the applied voltage. The combination effect of the electric field and meniscus oscillation can be utilized to significantly reduce the droplet diameter to less than 1/5 of the orifice diameter. The electric field extends the capability of DOD inkjet printing to cell-laden bioinks with high cell concentrations.

The gained knowledge of DOD inkjet printing has been further applied to vertical and horizontal printing of 3D vascular-like constructs using cell-laden bioink, which is a preliminary step towards the envisioned organ printing. It is found that the maximum achievable height of overhang structure depends on the inclination angle during vertical printing. To overcome the deformation-induced construct defect during horizontal printing, a predictive compensation approach has been proposed to fabricate 3D tubular constructs horizontally. Alginate cellular tubes have also been successfully printed with a satisfactory post-printing cell viability of 87% immediately after printing and after 24 hours of incubation.

Overall, this dissertation provides a better understanding of the pinch-off of viscoelastic alginate solutions, cell-laden droplet formation performance during DOD inkjet printing of bioink, effect of electric field on droplet formation under piezoactuation-based DOD inkjet printing, and fabrication process of 3D vascular-like constructs from bioink. This work would help better fabricate tissue-engineered blood vessels with a complex geometry using DOD inkjet printing.