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A Dual-Targeting Strategy Against ROS and GSK-3β With a PEGylated Fullerene/Smart Hydrogel Synergistic System for
Yijun Wang1,2, Jie Li1, Yusi Guo3,4
1Key Laboratory of Molecular Nanostructure and Nanotechnology & Beijing National Laboratory For Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, P.R. China.
Advanced Materials (Deerfield Beach, Fla.)
|May 15, 2026
Summary
This study introduces FPEG5, a novel fullerene derivative that combats oxidative stress and inflammation to enhance bone regeneration in diabetics. It reprograms macrophages and is delivered via a smart hydrogel for effective osteogenesis.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Nanotechnology
Background:
- Diabetic bone regeneration is hindered by oxidative stress and inflammation.
- A hostile microenvironment impairs healing processes.
Purpose of the Study:
- To develop a dual-function fullerene derivative (FPEG5) for diabetic bone regeneration.
- To investigate FPEG5's antioxidant and immunomodulatory effects.
- To create a responsive hydrogel for localized FPEG5 delivery.
Main Methods:
- Synthesized and characterized pentakis-PEGylated fullerene (FPEG5).
- Assessed FPEG5's ROS scavenging and immunomodulatory (GSK-3β/β-catenin/NF-κB) activity.
- Incorporated FPEG5 into a glucose- and ROS-responsive hydrogel.
- Evaluated FPEG5-hydrogel efficacy in vitro (osteogenic differentiation) and in vivo (diabetic calvarial defect model).
Main Results:
- FPEG5 demonstrated potent ROS scavenging and suppressed inflammatory pathways.
- FPEG5 reprogrammed M1 macrophages to an M2 phenotype.
- The hydrogel enabled on-demand FPEG5 release, promoting osteogenic differentiation.
- In vivo studies showed robust bone regeneration in diabetic defects.
Conclusions:
- FPEG5 acts as both an antioxidant and immunomodulator, targeting key pathways in diabetic bone loss.
- A smart hydrogel delivery system enhances localized therapeutic effects.
- This combined approach offers a promising strategy for diabetic osteoregeneration.
