Dynamic Covalent Hydrogels
From Fundamental Chemistry to Functional Biomaterials
Time: Fri 2025-11-14 10.00
Location: Kollegiesalen, Brinellvägen 8, Stockholm
Video link: https://kth-se.zoom.us/j/66891035930
Language: English
Subject area: Fibre and Polymer Science
Doctoral student: Taha Behroozi Kohlan , Polymerteknologi
Opponent: Associate Professor Matthew Baker, Maastricht University, Nederländerna
Supervisor: Professor Anna Finne Wistrand, Polymerteknologi; Assistant professor Fredrik Schaufelberger, Organisk kemi, Department of Chemistry, University of Warwick, Gibbet Hill Rd, Coventry, CV4 7AL UK
QC 20251016
Abstract
Regenerating human tissues has been a long-lasting goal in biomedical research. The complexity of the human body requires the convergence of chemistry, materials science, and biology towards this goal. The developed biomaterials should recapitulate native tissue environments to serve as implantable materials and realistic tissue models. A signature feature of native tissues is the dynamic characteristics in both biochemical and mechanical properties. Mimicking the dynamic nature of the native tissue is the main scheme of this thesis.
This thesis describes a route of benefitting from fundamental chemistry concepts and reactions to the development of biomaterials capable of affecting cellular response. The first part of the thesis focuses on dynamic covalent hydrogels based on hyaluronic acid and alginate prepared using imine, hydrazone, and oxime bonds through tailored crosslinking strategies. These dynamic bonds led to versatile and tunable properties in the hydrogels, such as viscoelasticity, self-healing, and injectability. The hydrogel dynamics, more specifically, the stress relaxation rate, were shown to greatly influence the cell spreading and morphology in cell cultures. Furthermore, imine bonds were used to modulate the release of an agent from the hydrogel matrices and prevent its abrupt release.
The second part of the thesis builds on the knowledge obtained in the first part to develop dynamic hydrogels with tailored microenvironments. Light-responsive moieties were used to enable the spatiotemporal tuning of biochemical and mechanical properties of the hydrogels with micrometer precision. To tune the biochemical properties, light was used to liberate binding sites for bioactive agents to couple to selective regions of the hydrogels. The binding was done using Schiff bases with various hydrolytic stabilities, offering tunability in the subsequent release of the agents. The mechanical properties of the microenvironments were altered by liberating a competitor to the implemented crosslinking chemistry of the hydrogels using light. This was done by photocaging the more nucleophilic crosslinker, changing the crosslinking chemistry upon liberation without altering the crosslinking density. The stiffness and viscoelasticity of hydrogel microenvironments as influential factors on cellular behavior were tuned with high spatiotemporal precision.
The findings demonstrate the progress from the design of dynamic covalent hydrogels to the precise and spatiotemporal control of hydrogel properties. This thesis bridges the gap between current hydrogel designs and the dynamic, heterogeneous properties of native tissue environments. The research offers a platform to create dynamic and heterogeneous biomaterials, closely replicating native tissues.