Abstract

Tissue culture models are invaluable tools commonly utilized to study biological systems, develop novel therapies and predict patient response to treatments. It is now widely accepted that tissue models should more closely mimic the properties of the in vivo environment to enhance clinical translatability of studies. Additionally, there is a growing demand for incorporating functional capabilities such as electronic conductivity into these models to digitally control or monitor cell behavior. However traditional electronic devices differ significantly from tissues as they offer dry, stiff (GPa) and two-dimensional surfaces. These characteristics can lead to the monitoring of abnormal or artificial cellular behavior. Therefore, there is a need to develop tissue-inspired bioelectronics for improved integration with tissue models. Conducting polymer hydrogels, like those made from poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), have emerged as promising candidates for bridging the gap between biology and technology, as these materials provide a more tissue-like conducting interface for cell interactions. However fabricating PEDOT:PSS hydrogels that have soft tissue-matching stiffness (1 – 100 kPa) while maintaining good electrical conductivity (>100 S/m) remains a challenge. Moreover, majority of studies have used PEDOT:PSS hydrogels as implantable, encapsulated 2D electrodes. Thus, the potential of these hydrogels to support 3D cell interactions in vitro is largely understudied. In this dissertation I employ a tissue-inspired approach to address these limitations. First I investigated whether manipulating the crosslinking of the PEDOT:PSS hydrogels influences their compatibility with cell culture processes. It was found that manipulating the concentration of the gelation agent influenced the aqueous stability, mechanical, and electrical properties of the hydrogels. With sufficient crosslinking, the hydrogels were stable for cell culture applications. Additionally, it was determined that further processing, such as serum incubation, was necessary for the hydrogels to support populations of primary cells on 2D PEDOT:PSS hydrogel substrates. Next, I created 3D printed bioelectronic scaffolds from PEDOT:PSS hydrogels to support the creation of 3D tissue models. In this study, I successfully developed scaffolds with tailorable stiffness in the tissue range (<100 kPa), high water content (>89%) and high conductivity (>200 S/m). These scaffolds supported 3D cell culture of fibroblasts and promoted inherent cell characteristics like extracellular matrix production. Finally, I created devices from these bioelectronic hydrogel scaffolds and investigated their ability to electronically detect changes in cancer cell behavior. I demonstrated that these devices could detect the presence or absence of cells and monitor temporal information on cell behavior including cell proliferation and chemotherapy drug-induced cell death. In the future, these devices could serve as on-chip technology that simultaneously supports tissue growth and provides an efficient method for screening cancer drugs and predicting patient response for precision medicine applications.

Committee Chair

Alexandra Rutz

Committee Members

Chuan Wang; Cory Berkland; Mary Mullen; Srikanth Singamaneni

Degree

Doctor of Philosophy (PhD)

Author's Department

Biomedical Engineering

Author's School

McKelvey School of Engineering

Document Type

Dissertation

Date of Award

12-10-2025

Language

English (en)

Download

Available for download on Wednesday, December 08, 2027

Share

COinS