NO-releasing double-crosslinked responsive hydrogels accelerate the treatment and repair of ischemic stroke.
10.1016/j.apsb.2025.01.005
- Author:
Wen GUO
1
;
Cheng HU
2
;
Yue WANG
2
;
Wen ZHANG
2
;
Shaomin ZHANG
1
;
Jin PENG
1
;
Yunbing WANG
2
;
Jinhui WU
1
Author Information
1. Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
2. National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Med-X Center for Materials, Sichuan University, Chengdu 610064, China.
- Publication Type:Journal Article
- Keywords:
Angiogenesis;
Anti-inflammation;
Double-crosslinked;
Hydrogel;
Ischemic stroke;
Macrophage migration inhibitory factor;
Neuroprotective;
Nitric oxide
- From:
Acta Pharmaceutica Sinica B
2025;15(2):1112-1125
- CountryChina
- Language:English
-
Abstract:
Stroke is a global disease that seriously threatens human life. The pathological mechanisms of ischemic stroke include neuroinflammation, oxidative stress, and the destruction of blood vessels at the lesion site. Here, a biocompatible in situ hydrogel platform was designed to target multiple pathogenic mechanisms post-stroke, including anti-inflammation, anti-oxidant, and promotion of angiogenesis. Double-crosslinked responsive multifunctional hydrogels could quickly respond to the pathological microenvironment of the ischemic damage site and mediate the delivery of nitric oxide (NO) and ISO-1 (inhibitor of macrophage migration inhibitory factor, MIF). The hydrogel demonstrated good biocompatibility and could scavenge reactive oxygen species (ROS) and inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-10 (IL-10), and MIF. In a mouse stroke model, hydrogels, when situated within the microenvironment of cerebral infarction characterized by weak acidity and elevated ROS release, would release anti-inflammatory nanoparticles rapidly that exert an anti-inflammatory effect. Concurrently, NO was sustained release to facilitate angiogenesis and provide neuroprotective effects. Neurological function was significantly improved in treated mice as assessed by the modified neurological severity score, rotarod test, and open field test. These findings indicate that the designed hydrogel held promise for sustained delivery of NO and ISO-1 to alleviate cerebral ischemic injury by responding to the brain's pathological microenvironment.
