ORCID Identifier(s)

0009-0005-2139-6299

Graduation Semester and Year

Spring 2026

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Yi Hong

Second Advisor

Jun Liao

Third Advisor

Liping Tang

Fourth Advisor

Zui Pan

Fifth Advisor

Michael Cho

Abstract

Conductive biomaterials have raised as a promising class of materials for restoring electrical signaling in damaged tissues, particularly in cardiac and neural applications, and bioelectronics and sensors. Current approaches incorporate conductive components such as intrinsically conductive polymers, carbon nanomaterials and metallic nanomaterials into biocompatible scaffolds to enhance electrophysiological coupling in engineered tissues. While these materials improve electrical propagation and cell proliferation, significant limitations persist. Many conductive biomaterials exhibit poor biodegradability, potential cytotoxicity and mechanical mismatch with native elastic tissue, restricting long-term integration. This thesis addresses these challenges through the systematic design and development of conductive biodegradable materials across multiple structural platforms, including films, porous scaffolds, intrinsically conductive hydrogels, and conductive composite hydrogels.

For the beginning, a self-doped conductive biodegradable polyurethane (SCPU) system was comprehensively optimized by investigating the effects of diisocyanate structure, solvent system, and reaction temperature. Spectroscopic analysis confirmed the incorporation of aniline trimer (AT) in its emeraldine state into the polymer backbone. Among all three diisocyanates, including hexamethylene diisocyanate, 1,4-butane diisocyantae, and isophorone diisocyanate, SCPU synthesized with hexamethylene diisocyanate coupling agent, 2,2-Bis(hydroxymethyl)propionic acid (DMPA), poly(caprolactone) diol and AT in the co-solvent of tetrahydrofuran and N-methyl-2-pyrrolidone (THF/NMP) exhibited the most balanced performance, achieving a tensile strength of 30.9±5.2 MPa, Young’s modulus of 34.9±2.5 MPa and conductivity of 9.3±2.8×10⁻5 S/m at dry state and 7.3±1.2×10⁻3 S/m after PBS balance. Comparing solvents of THF/NMP and dimethyl sulfoxide (DMSO), SCPUs synthesized in DMSO solvent enhanced conductivity up to 3.8±1.5×10⁻2 S/m. However, they compromised mechanical integrity, highlighting an inherent trade-off. Elevated reaction temperature further influenced performance. SCPU synthesized at 120 °C enhanced mechanical strength and slowed degradation. Porous scaffolds fabricated from hexamethylene diisocyanate coupled SCPU synthesized in THF/NMP co-solvent exhibited interconnected architectures with an average pore size of 153.0±33.7 μm, and initial modulus and ultimate strength of 153.4±7.6 kPa and 43.9±6.2kPa respectively. Enzymatic degradation studies showed that the scaffolds retained notably more mass than the control PU-HDI of 79.4±2.1 % vs. 69.3±2.2 % after a 14 day study. In vitro H9c2 cell studies demonstrated good cytocompatibility, and also showed good proliferation on both SCPU films and scaffolds. Overall, these results confirmed an optimized SCPU system and demonstrated its potential as a versatile conductive biodegradable platform for future applications in tissue repair.

An intrinsically conductive biodegradable hydrogel, PEGCL-ATG, was developed. Briefly, poly(caprolactone) (PCL) is chemically incorporated into poly(ethylene glycol) (PEG) via ring opening polymerization of ε-caprolactone to form PCL-PEG-PCL triblock polymer diol. The PCL-PEG-PCL diol was then reacted with hexamethylene diisocyanate and DMPA to form a prepolymer, which subsequently reacted with AT and (hydroxyethyl)methacrylate (HEMA) to form PEGCL-ATG precursor. PEGCL-ATG was formed through three different initiation strategies, specifically, photo initiation via lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) photo-initiator, redox initiation via ammonium persulfate (APS) and N, N, N′, N′-tetramethyl ethylenediamine (TEMED) (APS/TEMED) and thermal initiation via 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPC) thermal initiator. PEG-ATG exhibited reduced swelling (167.0±7.0 %) compared to 276.3±12.2 % of control PEG hydrogel. Among the three hydrogels, PEG-ATG exhibited the highest elasticity with a storage modulus of 1443.9±12.4 Pa, followed by PEG-G at 1139.9±9.6 Pa, and PEGCL-ATG of 848.3±7.3 Pa. Conductivities of all hydrogels were on the order of 10-2 S/m under physiological conditions, and PEGCL-ATG exhibited the highest conductivity due to improved conductive domain connectivity. PEGCL-ATG showed a reduced mechanical property compared to PEG-ATG likely due to the incorporation of the long PCL-PEG-PCL triblock segment. PEGCL-ATG exhibited ~40 % mass loss over 14 days. Cytocompatibility assessment remained high across all formulations. Additionally, the crosslinking strategy significantly influenced mechanical and electrical performance. Specifically, the LAP photoinitiator resulted in a Young’s modulus of 2544.4±21.8 Pa and a conductivity of 5.8±0.7×10-2 S/m; APS/TEMED redox system showed 3892.4±17.6 Pa and 1.8±0.2×10-2 S/m in mechanical strength and conductivity, whereas AIPC, the thermal initiator, yielding the optimal balance between mechanical strength, 5210.4±10.2 Pa, and conductivity, 5.2±0.4×10-2 S/m. These results demonstrated that PEGCL-ATG as a promising elastic and biodegradable conductive hydrogel platform with opportunities to be further optimized for tissue repair and bioelectronics.

For future work, SCPU scaffolds will be utilized in rat or pig myocardial infarction (MI) models to evaluate the therapeutic potential of this scaffold including host tissue responses and cardiac function restoration. Electroactive nature of the scaffold will also be investigated for its capacity in improving electrical signal propagation across the infarct zone. PEGCL-ATG will also be tested on a rat MI model to assess its effects on cardiac repair and functional recovery, In addition, its potential in bioelectronics will be explored, particularly as a soft conductive matrix for signal transmission, sensing and integration with flexible electronic platforms. An elastic conductive hydrogel nanocomposite has been preliminarily prepared by adding NH2-MWCNT into an elastic PCL-PEG-PCL based hydrogel. The effects of polymer concentration, network architecture and CNT loadings will be systematically evaluated in terms of electrical, mechanical and biological properties. Preliminary studies indicate that the introduction of CNTs substantially enhances electrical conductivity while concurrently improving mechanical robustness and structural stability, without compromising cytocompatibility. Building on these findings, the proposed work aims to identify an optimal balance between conductivity, mechanical integrity, degradation behavior and biological performance. This proof-of-concept study aims to establish a conductive hydrogel composite with improved physical and chemical properties for bioelectronics.

Overall, this thesis establishes a comprehensive framework for the rational design of conductive biomaterials, demonstrating how molecular structure, network architecture and composite integration to achieve the balance among electrical, mechanical, and biological properties. The developed systems collectively overcome key limitations of conventional conductive biomaterials, offering a soft and elastic biodegradable biomaterial platform with potentials for applications in tissue repair and bioelectronics.

Keywords

Biomaterials, Conductive Polyurethane, Hydrogel, Intrisically Conductive Hydrogel, Self-doped Polymers, Aniline Trimer, Polycaprolactone, Multi-arm Hydrogel, Cardiac Repair, Bioelectronics

Disciplines

Biology and Biomimetic Materials | Biomaterials | Biomedical Engineering and Bioengineering | Molecular, Cellular, and Tissue Engineering | Nanoscience and Nanotechnology | Polymer and Organic Materials | Polymer Science

Comments

Above all, I would like to express my deepest and most sincere gratitude to my supervisor, Dr. Yi Hong, for his invaluable guidance, insight, and support throughout my doctoral research. His perspective has profoundly shaped the way I think as a researcher, encouraging me to ask deeper questions, refine my ideas with rigor, and approach scientific challenges with both critical reasoning and intuition. His mentorship has been instrumental in my growth into a more capable, independent, and confident researcher.

I would also like to sincerely acknowledge all members of our laboratory, as well as our collaborators, for their hard work, support, and valuable contributions to my research. Their assistance, discussions, and encouragement have greatly enriched this work.

Finally, I gratefully acknowledge the generous financial support from the NIH, NSF, and DMR, which made this research possible.

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