Date Approved

9-23-2024

Embargo Period

9-24-2025

Department

Biomedical Engineering

College

Henry M. Rowan College of Engineering

Advisor

Sebastian Vega, Ph.D.

Keywords

3D hydrogels, mesenchymal stem cell, biomaterial scaffolds

Disciplines

Biomedical Engineering and Bioengineering | Chemical Engineering | Medicine and Health Sciences

Abstract

Hydrogels are soft, highly hydrated polymeric networks commonly used as biomaterial scaffolds in tissue engineering. To mimic the extracellular matrix of tissues, hydrogels can be chemically modified to incorporate either bioactive molecules such as peptides, or physically modified with crosslinkers to alter hydrogel stiffness and degradation. Hydrogels with defined characteristics can be synthesized using chemical reaction schemes such as photo-click chemistry, which offers spatial and temporal control over biochemical and physical properties. The goal of this thesis is to leverage thiol-norbornene click chemistry, a subtype of photo-click chemistry, to develop 3D hydrogels with biochemical and biophysical cues that guide mesenchymal stem cell (MSC) mechanosensing and differentiation. Macromers from either naturally derived (hyaluronic acid, HA) or synthetic (polyethylene glycol, PEG) origin were modified with norbornene groups (Nor) and covalently crosslinked with di-thiolated molecules to form hydrogels amenable to biochemical functionalization with mono-thiolated peptides. PEG-Nor and HA-Nor hydrogels demonstrated a broad range of mechanical properties and were functionalized with adhesive and bone-inducing peptides to promote MSC adhesion and to guide 3D osteogenic differentiation. The thiol-norbornene hydrogels designed in this thesis are highly tunable and serve as a cell-culture platform with broad applications in studying 3D cellular mechanosensing and in developing bone-producing materials.

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Available for download on Wednesday, September 24, 2025

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