Date of Award

2026

Abstract

Supramolecular hydrogels have emerged as a versatile class of biomaterials capable of mimicking the dynamic behavior of natural tissues due to their inherent hydrophilicity, stimuli-responsiveness, and viscoelastic behavior. However, achieving both biocompatibility and mechanical tunability remains a challenge. This work utilizes DNA intercalation to create a programmable, sustainable hydrogel platform. By utilizing the reversible insertion of planar aromatic molecules between DNA base pairs, we demonstrate that the network’s dissociation kinetics and thermodynamic response are directly governed by the intercalator structure, offering a highly tunable strategy for stimuli-responsive biomaterials.To demonstrate the versatility of double stranded DNA (dsDNA) intercalating supramolecular hydrogels (DISHs), we crosslinked dsDNA using bifunctional polyethylene glycol (MW ≈2,000 Da) capped with intercalators of varying hydrophobicity, charge, and size: acridine, psoralen, thiazole orange, and phenanthridine. Notably, acridine-based cross-linkers displayed invariant and even increasing relaxation times with temperature, suggesting an entropically-driven binding mechanism. In contrast, the other three intercalators exhibited enthalpic behavior, where increased temperature accelerated bond dissociation. This platform establishes a new material system where a broad set of thermal and viscoelastic responses can be obtained due to the vast library of available intercalating molecules. To further expand the utility of DISHs as thermal-stiffening materials, we investigated acridine-based DISH thermodynamics through the control of pH and ionic strength. We demonstrated that high ionic strength effectively screens electrostatic repulsion, allowing positive entropic contributions to dominate the binding equilibrium. This shift enables a temperature-stabilization effect, where elasticity and relaxation times are enhanced with increasing heat. These results provide a highly stimuli-responsive platform for engineering hydrogels that resist thermal softening, achieving mechanical robustness across a broad range of environmental conditions. To expand the use of DISHs as tissue-mimicking biomaterials, we leverage the dual-functionality of psoralen DNA binding. Psoralen-based DISHs were formed by crosslinking DNA using tetrafunctional PEG (Mw ≈10,000 Da). Initially, psoralen intercalation produces an extrudable, self-healing dynamic network with tunable mechanical properties via crosslinker valency and concentration. Upon UVA irradiation (365 nm), psoralen undergoes a [2+2] cycloaddition with thymine to form covalent, inter-duplex bridges. Since this crosslinking occurs without disrupting the DNA phosphodiester backbone, the hydrogel retains fully enzymatic degradability, permitting full digestion for the recovery of cultured cells. Together, the work in this dissertation establishes DNA intercalating supramolecular hydrogels as highly tunable, biocompatible materials. These results emphasize the expansive properties that can be accomplished in these systems; from heat stable networks to extracellular matrix (ECM) mimicking, cell compatible scaffolds- this research accomplishes a wide breadth of materials through simple selection of intercalator.

Document Type

Dissertation

First Advisor

Nathan J Oldenhuis

Second Advisor

Erik Berda

Third Advisor

Anyin Li

Department or Program

Chemistry

Degree Name

Doctor of Philosophy

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