An injectable and adaptable hydrogen sulfide delivery system for modulating neuroregenerative microenvironment

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Peripheral nerve regeneration is challenging due to the complex microenvironment.
• Existing nerve scaffolds often fail to adapt, leading to poor outcomes.
• A strategy is needed to actively modulate the regenerative environment.

Purpose of the Study:

• To develop a ROS-responsive hydrogel system for on-demand hydrogen sulfide (H2S) release.
• To investigate the efficacy of this system in promoting peripheral nerve regeneration and neuroprotection.
• To explore the underlying mechanisms of H2S-mediated repair.

Main Methods:

• Fabrication of a multi-component hydrogel system: H2S donor (peroxyTCM) in a ROS-responsive polymer (mPEG-PMet) within a temperature-sensitive hydrogel (mPEG-PA-PP).
• In situ H2S release triggered by endogenous reactive oxygen species (ROS) at the injury site.
• Evaluation of the hydrogel's effects on peripheral nerve injury (PNI) repair, including neuroregeneration, neuroprotection, and functional recovery.

Main Results:

• The developed hydrogel system successfully released H2S in response to ROS.
• H2S release significantly promoted peripheral nerve regeneration and functional recovery.
• Key mechanisms included inflammation inhibition, oxidative stress reduction, enhanced angiogenesis, and improved mitochondrial function.

Conclusions:

• The "pleiotropic gas transmitter" strategy using ROS-triggered H2S release shows significant promise for peripheral nerve repair.
• This adaptive approach effectively modulates the regenerative microenvironment, offering new opportunities in tissue engineering.
• The multi-functional hydrogel system provides concurrent neuroprotection and neuroregeneration.