A thermo-sensitive hydrogel targeting macrophage reprogramming for sustained osteoarthritis pain relief.
10.1016/j.apsb.2025.07.024
- Author:
Yue LIU
1
;
Kai ZHOU
2
;
Xinlong HE
2
;
Kun SHI
2
;
Danrong HU
2
;
Chenli YANG
2
;
Jinrong PENG
2
;
Yuqi HE
3
;
Guoyan ZHAO
3
;
Yi KANG
3
;
Yujun ZHANG
1
;
Yue'e DAI
4
;
Min ZENG
5
;
Feier XIAN
5
;
Wensheng ZHANG
1
;
Zhiyong QIAN
2
Author Information
1. Department of Anaesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China.
2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
3. Laboratory of Anaesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anaesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China.
4. Department of Anaesthesiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
5. West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
- Publication Type:Journal Article
- Keywords:
Chronic pain;
Dorsal root ganglion;
Drug delivery;
Macrophages;
Neuroinflammation;
Osteoarthritis;
Pain management;
Thermo-sensitive hydrogel
- From:
Acta Pharmaceutica Sinica B
2025;15(11):6034-6051
- CountryChina
- Language:English
-
Abstract:
Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.
