Date of Award

Fall 2026

Abstract

Gelatin-based microgels are modular biomaterial building blocks that can be injected and assembled into three-dimensional scaffolds for tissue engineering. Their performance, however, is limited by the transport properties of individual particles, the difficulty of directly encapsulating cells while preserving viability and secondary crosslinking capacity, and the limited ability of passive scaffolds to provide externally controlled physical stimulation. This dissertation investigated three complementary strategies to expand the structural and functional capabilities of gelatin-based microgel systems. First, thermally stable porous gelatin/alginate microgels were produced using calcium-mediated ionic crosslinking and subsequently annealed with microbial transglutaminase. The resulting assemblies maintained internal porosity at physiological temperature, increased macromolecular penetration and release, and provided additional cell-accessible space while retaining bulk mechanical properties comparable to nonporous gelatin microgel assemblies. Human dermal fibroblasts infiltrated the internal pores, and RNA sequencing indicated distinct transcriptional responses of inflammatory-signal-primed mesenchymal stem cells in porous and nonporous environments. Second, direct fabrication of cell-laden gelatin-based microgels was evaluated using bulk water-in-oil emulsification and microfluidic processing. Bulk emulsification demonstrated the feasibility of locating cells within the microgel building blocks but produced variable particle size and generally low or inconsistent fibroblast viability. Microfluidic processing improved cell survival under the tested conditions, although premature gelatin gelation disrupted stable droplet formation and prevented reproducible production of uniform microgels. Third, magnetically responsive gelatin microgels were prepared by incorporating iron oxide nanoparticles. The particles retained magnetic responsiveness after enzymatic annealing and supported fibroblast and mesenchymal stem cell viability. Osteogenic studies showed greater calcium accumulation in magnetic microgel groups than in unmodified gelatin controls, with the magnetic microgel group exposed to a static magnetic field exhibiting the highest exploratory live-cell-coverage-normalized calcium index. Because magnetic-field strength, force transmission, and cell number were not fully quantified, these findings are interpreted as preliminary evidence rather than proof of a defined mechanotransduction mechanism. Collectively, the studies establish porous, cell-laden, and magnetically responsive gelatin microgels as complementary design directions and identify the fabrication and quantitative validation needed to combine them into multifunctional tissue-engineering scaffolds.

Document Type

Dissertation

First Advisor

Kyung Jea Jeong

Second Advisor

Nivedita Gupta

Third Advisor

Young Jo Kim

Department or Program

Chemical Engineering

Degree Name

Doctor of Philosophy

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