Graduation Semester and Year

Spring 2026

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Materials Science and Engineering

Department

Materials Science and Engineering

First Advisor

Dr. Kyungsuk Yum

Abstract

The mechanical properties of three-dimensional (3D) bioprinted constructs critically determine cellular behavior, including viability, proliferation, and morphology. Matching the mechanical properties of engineered tissue constructs to the diverse landscape of native tissues remains a central challenge in biofabrication, as tuning stiffness to mimic the extracellular matrix (ECM) often compromises printability. This dissertation presents a modular platform that utilizes the triblock copolymer poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) (PEO−PPO−PEO) as a universal fugitive carrier to decouple extrusion rheology from the final constructs’ mechanical properties. By employing microbial transglutaminase (mTG), a biocompatible enzyme that catalyzes covalent protein cross-linking, we established a “soft spectrum” (≤6 kPa) of gelatin-based bioinks. Stiffness was precisely tuned by varying mTG concentration and crosslinking duration without compromising cytocompatibility, covering a range of the soft mechanical environments. To address stiffer physiological environments, we developed a “stiff spectrum” (up to 24 kPa) using a dual-crosslinked gelatin methacryloyl (GelMA)/gelatin hydrogel system that combines enzymatic and photo-crosslinking. Mechanical characterization confirmed that the construct stiffness is adjustable over a physiologically relevant range, from ultra-soft neural analogs to rigid pre-calcified bone and fibrotic tissue analogs. Biological evaluation using encapsulated NIH 3T3 fibroblasts confirmed high cytocompatibility, with viability maintained above 90% across all crosslinking conditions. Cells exhibited stiffness-dependent spreading behavior, validating the platforms’ ability to guide cellular responses through mechanotransductive signaling. These results demonstrate that integrating enzymatic mTG crosslinking and dual crosslinking within a fugitive carrier system offers a versatile, reproducible, and controllable approach to engineering 3D bioprinted tissues, with significant implications for mechanobiology research and regenerative medicine.

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Available for download on Wednesday, May 10, 2028

Share

COinS