Date Approved

1-23-2023

Embargo Period

1-24-2024

Document Type

Dissertation

Degree Name

Ph.D. Doctor of Philosophy

Department

Mechanical Engineering

College

Henry M. Rowan College of Engineering

Advisor

Mitja Trkov, Ph.D. and Amir K Miri, Ph.D., Co-chairs

Committee Member 1

Wei Xue, Ph.D.

Committee Member 2

Sagnik Basuray, Ph.D.

Committee Member 3

Gary Thompson, Ph.D.

Keywords

Bioprinting, Digital-light-processing, High-throughput Screening, Hydrogel Models, Microfluidics

Subject(s)

Drug development

Disciplines

Biomedical Engineering and Bioengineering | Mechanical Engineering

Abstract

The microfluidic enabled the integration of engineered miniaturized tissue models for drug screening. Conventional polydimethylsiloxane or plastic-based devices require multiple fabrication steps, which are challenging. We developed a 3D bioprinting approach to create prototypes of hydrogel-based multi-material microfluidic devices integrated with microtissue models. The approach utilizes poly(ethylene glycol) diacrylate and gelatin-methacryloyl to create microfluidic chips using multi-material bioprinting capacity with a high resolution of 15µm on x-y and 50µm on the z-axis and post-printing viability of >90%. We demonstrated easy regulation of stiffness from 24±5 kPa to 1,180±9 kPa and burst pressure from 16±1kPa to 256±19 kPa in the chip by regulating control parameters, such as hydrogel mass concentration, photoinitiator ratio, and light exposure. This easily scalable device accommodates different microtissue gradients and compositions, multiple bioreactors, drug gradient generators, and electrodes within a single chip. We expanded the capacity to 8 parallel bioreactors in the same microfluidic chip and tested the drug's effect in producing reactive oxygen species in the chip. We printed a hydrogel-based electrode using our approach and PEDOT:PSS. The electrode showed a conductivity of 1.5 x10^-2 S/m. The microfluidic device allows the diffusion of molecules, a cell-sustainable dynamic environment, and biochemical analysis within the device. This dissertation establishes the groundwork for rapidly creating a scalable biomimetic microfluidic device for the parallel screening of various components.

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