Oxidatively Responsive Chain Extension to Entangle Engineered Protein Hydrogels.

Area of Science:

• Biomaterials Engineering
• Polymer Science
• Protein Engineering

Background:

• Precise control over mechanical properties like stiffness, toughness, and extensibility is crucial for engineering protein hydrogels for medical use.
• Existing hydrogel networks often struggle with stability in physiological environments.

Purpose of the Study:

• To demonstrate topological entanglement as a strategy to enhance the mechanical properties and tunability of transient protein hydrogels.
• To investigate the impact of redox-stimuli on the entanglement and mechanical response of the hydrogels.

Main Methods:

• Constructing transient hydrogel networks using coiled-coil interactions and cysteine residue coupling for chain extension and entanglement.
• Utilizing reversible disulfide bonds to enable redox-triggered switching of entanglement.
• Characterizing mechanical properties including stiffness, toughness, extensibility, creep resistance, and erosion rate.

Main Results:

• Topological entanglement significantly enhanced creep resistance (7.2-fold) and suppressed erosion (5.8-fold), improving mechanical stability.
• Hydrogels achieved high toughness (65,000 J m⁻³) and extensibility (~3,000% strain) with only a modest increase in stiffness.
• The entanglement effect was reversible and controllable via redox stimuli.

Conclusions:

• Redox-triggered topological entanglement is an effective strategy for creating mechanically robust and tunable protein hydrogels.
• This approach offers a single-network solution for achieving mechanical enhancements comparable to double-network hydrogels.
• The developed hydrogels show promise for applications requiring tough, soft, and responsive biomaterials, such as tissue simulants.