Injectable Metal-Free Carbon Dot-Integrated Hydrogel for Regulating Inflammation via Macrophage Metabolic...

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Spinal cord injury (SCI) triggers oxidative stress and inflammation, hindering nerve regeneration.
• Current nanozymes for SCI therapy face neurotoxicity concerns due to metal ions.
• Developing safe and effective therapies is crucial for functional restoration after SCI.

Purpose of the Study:

• To develop a metal-free nanozyme system for SCI therapy.
• To investigate the potential of carbon dots (D-CDs) to mitigate oxidative stress and inflammation.
• To create an injectable hydrogel for sustained delivery of D-CDs.

Main Methods:

• Synthesized metal-free carbon dots (D-CDs) and formulated an injectable chitosan-based hydrogel (QP hydrogel).
• Evaluated D-CDs' ability to eliminate reactive oxygen species (ROS) and reprogram macrophage metabolism in vitro.
• Assessed the D-CDs@QP hydrogel's efficacy in promoting M2 macrophage polarization, neurogenesis, and functional recovery in a mouse SCI model.

Main Results:

• D-CDs effectively eliminated ROS and reprogrammed macrophage metabolism via P53 signaling, promoting a pro-regenerative phenotype.
• The D-CDs@QP hydrogel facilitated M2 macrophage polarization and enhanced neurogenesis while suppressing astrogliosis in vitro.
• In vivo studies showed significant motor and bladder function recovery in mice with SCI treated with D-CDs@QP.

Conclusions:

• The metal-free carbon nanozyme-integrated hydrogel system offers a promising therapeutic strategy for SCI.
• This approach effectively combats neuroinflammation, stimulates neuroregeneration, and promotes functional recovery post-SCI.
• The D-CDs@QP hydrogel system demonstrates high clinical feasibility for treating spinal cord injuries.