Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation

Area of Science:

• Biomaterials Science
• Cell Therapy Engineering
• Tissue Engineering

Background:

• Cell membrane re-engineering enhances therapeutic cell functionality.
• Limited examples exist for displaying enzymes on cell membranes for extracellular matrix assembly.

Purpose of the Study:

• To develop a self-contained matrix-forming system using engineered cell membranes.
• To display active enzymes on human mesenchymal stem cells for fibrin hydrogel formation.

Main Methods:

• Synthesized a membrane-binding supercationic thrombin-polymer surfactant complex.
• Modified human mesenchymal stem cell membranes to display the thrombin construct.
• Assessed fibrin hydrogel nucleation and growth at physiological fibrinogen concentrations.

Main Results:

• Achieved spontaneous fibrin hydrogel nucleation and growth using engineered cells.
• Demonstrated that the cellular fibrin hydrogel constructs support osteogenic and adipogenic differentiation.
• Observed that the resulting monoliths exhibit Young's moduli reflecting their extracellular matrix composition.

Conclusions:

• Developed a novel cell membrane-based system for extracellular matrix assembly.
• Engineered cells can form functional hydrogel constructs with tunable mechanical properties.
• This approach holds promise for next-generation cell therapies and tissue engineering applications.