Tuning viscoelasticity of dynamic covalent hydrogels for human tissue modeling

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Biomedical Engineering

Background:

• Three-dimensional (3D) *in vitro* tissue culture models are crucial for biomedical research.
• Hydrogel scaffolds offer tunable viscoelastic properties influencing cell behavior.
• Dynamic covalent chemistry (DCC) hydrogels exhibit stress relaxation but often erode quickly.

Purpose of the Study:

• To develop DCC hydrogels with independently controlled stiffness and stress relaxation for long-term 3D culture.
• To explore molecular parameters (molecular weight, degree of functionalization) as alternatives to faster bond kinetics for tuning viscoelasticity.
• To investigate the impact of scaffold viscoelasticity on encapsulated human neural progenitor cells.

Main Methods:

• Developed and validated a modified theoretical model for gel viscoelasticity.
• Synthesized a two-component DCC hydrogel using modified hyaluronic acid and elastin-like protein.
• Utilized the tunable hydrogel platform to culture encapsulated human neural progenitor cells.

Main Results:

• Demonstrated independent control over hydrogel stiffness and stress relaxation rates by adjusting molecular parameters.
• Achieved tunable viscoelastic properties without compromising gel stability or promoting rapid erosion.
• Observed the impact of scaffold viscoelasticity on human neural progenitor cell behavior.

Conclusions:

• Expanded the molecular design principles for DCC hydrogels.
• Created a versatile platform for long-term 3D *in vitro* models with tunable viscoelasticity.
• Provided insights into cell-scaffold interactions within viscoelastic environments.