Celastrol-Loaded Conductive Hydrogel Mitigates Myocardial Ischemia-Reperfusion Injury and Restores...

Area of Science:

• Biomaterials Science
• Cardiovascular Research
• Regenerative Medicine

Background:

• Myocardial ischemia-reperfusion injury (MIRI) poses a significant clinical challenge, impacting patient outcomes after revascularization.
• Celastrol (CLT), a potent antioxidant, shows promise for MIRI treatment but faces limitations due to poor solubility and potential toxicity.
• Localized and sustained drug delivery systems are needed to overcome CLT's limitations and enhance therapeutic efficacy.

Purpose of the Study:

• To develop an injectable, conductive hydrogel platform (FGPC) for localized and sustained delivery of celastrol (CLT).
• To evaluate the efficacy of FGPC in mitigating MIRI through antioxidant and anti-inflammatory mechanisms.
• To assess the potential of FGPC for promoting cardiac repair and improving cardiac function post-MIRI.

Main Methods:

• Fabrication of an injectable FGPC hydrogel composed of F127DA, GelMA, PEDOT:PSS, and CLT.
• In vitro assessment of FGPC's physical properties, biocompatibility, and antioxidant capacity.
• In vivo evaluation of FGPC in a rat MIRI model, including histological, transcriptomic, and functional analyses.

Main Results:

• FGPC hydrogel demonstrated favorable mechanical properties, electrical conductivity, local retention, and controlled CLT release.
• In vitro studies showed FGPC effectively reduced reactive oxygen species (ROS) and supported cardiomyocyte health.
• In vivo, FGPC treatment attenuated MIRI-induced oxidative stress, inflammation, and neutrophil extracellular trap formation, leading to improved cardiac function, reduced fibrosis, and enhanced angiogenesis without systemic toxicity.

Conclusions:

• The developed FGPC hydrogel platform enables localized and sustained delivery of CLT, effectively addressing MIRI.
• FGPC combines CLT's antioxidant effects with electrical support, offering a promising therapeutic strategy for myocardial repair.
• This approach presents a potential solution for improving outcomes in patients suffering from myocardial ischemia-reperfusion injury.