Self-assembling multidomain peptide hydrogels accelerate peripheral nerve regeneration after crush injury

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Peripheral nerve injuries significantly damage the extracellular matrix (ECM), hindering natural recovery.
• Existing treatments for severe peripheral nerve injuries are limited, impacting patient quality of life.
• Multidomain peptide (MDP) hydrogels are known for soft tissue regeneration but their effect on nerve repair is unexplored.

Purpose of the Study:

• To investigate the potential of MDP hydrogels for peripheral nervous system (PNS) regeneration.
• To design and synthesize novel MDPs mimicking ECM components and growth factors.
• To evaluate the efficacy of MDP hydrogels in promoting nerve repair in vivo.

Main Methods:

• Eight MDPs were designed and self-assembled into injectable nanofibrous hydrogels.
• In vitro screening identified lysine-based MDPs that enhance neurite outgrowth.
• Rat sciatic nerve crush injury model used to assess in vivo efficacy of MDP hydrogels.

Main Results:

• MDP hydrogels enhanced macrophage recruitment and degraded over time at injury sites.
• Specific MDPs (K2, K2-IIKDI, K2-IKVAV) significantly accelerated functional recovery and remyelination.
• MDPs demonstrated the ability to promote neurite outgrowth and a pro-regenerative response.

Conclusions:

• MDP hydrogels are effective biomaterials for promoting peripheral nerve regeneration.
• These findings highlight the therapeutic potential of MDPs for nerve repair and other applications.
• MDPs can enhance neurite outgrowth and orchestrate a pro-regenerative cellular response.