Researcher(s)
- Shelby Nelson, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Joseph Fox, Chemistry and Biochemistry, University of Delaware
Abstract
For many biomedical applications, 3D cell cultures are used through creating microenvironments for in vitro tissue studies. To create an environment that is biomimetic to extracellular matrices, a dynamic system that imitates the viscoelasticity and stiffness of human tissue is needed. The lamina propria layer of the vocal fold tissue is responsible for the vibration that causes the human voice to be produced. Different pathologies can cause the natural, vibrating nature of the vocal fold to be harmed, leading to various vocal disorders. Creating a 3D tissue culture model of the vocal fold could aid in discovering treatments for vocal fold disorders and further studies of tissue function. The Fox Group at the University of Delaware has recently discovered a new type of reversible covalent chemistry utilizing the tetrazine ligation. Synthesized thiomethyltetrazines can be used to create a dynamic environment which then can be turned off through bioorthogonal chemistry. The goal of this work is to use the thiomethyltetrazine reversible covalent chemistry as a way to make hydrogels capable of supporting 3D tissue culture. This bioorthogonal reaction has rapid kinetics and can occur by introducing trans-cyclooctene at a specific time to the system. The hydrogel system consists of using a hyaluronic acid-thiol backbone with thiomethyltetrazines attached. The dynamic, reversible nature is seen by SNAr chemistry between thiols and thiomethyltetrazine. The addition of trans-cyclooctene leads to the bioorthogonal reaction, turning this into an irreversible system, potentially increasing the stiffness of the hydrogel. Spatiotemporal control over this bioorthogonal chemistry, specifically the tetrazine ligation, can be used to alter the mechanical properties of hydrogels being used for 3D tissue culture.