In vivo mechano-tissue engineering by hydrogels capable of transmitting intercellular mechanical stress

Area of Science:

• Mechanobiology
• Tissue Engineering
• Biomaterials Science

Background:

• Tissue engineering aims to restore tissue function using cells and biomaterials.
• Cellular mechanosensors, like integrins, play a crucial role in tissue regeneration.
• Current methods often rely on specific ligands to activate mechanosensors, limiting control.

Purpose of the Study:

• To develop a novel method for eliciting regenerative responses in transplanted cells.
• To utilize in vivo mechanical stress for activating cellular mechanosensors.
• To establish a stable and reliable linkage between cells and biomaterials.

Main Methods:

• Introduction of azide groups into cellular integrins.
• Modification of hydrogels with cyclooctyne (DBCO) groups.
• Formation of bioorthogonal click reactions to create irreversible integrin-hydrogel covalent bonds.

Main Results:

• Demonstration of a stable and irreversible covalent linkage between integrins and hydrogels.
• Confirmation that the integrin-hydrogel linkage remains active under various conditions (stress intensity, cell cycle, environment).
• Evidence of rapid and reliable transmission of mechanical stress to the cell nucleus, inducing regeneration.

Conclusions:

• The developed method effectively uses mechanical stress for cell-mediated regeneration in tissue engineering.
• Bioorthogonal click chemistry provides a robust strategy for cell-material integration.
• This approach offers a new paradigm for controlling cellular behavior and promoting tissue repair.