Salidroside-loaded metal-organic frameworks hydrogel to improve cardiac allograft function

Area of Science:

• Biomaterials Science
• Cardiovascular Surgery
• Regenerative Medicine

Background:

• Ischemia-reperfusion injury (IRI) significantly impairs primary graft function after heart transplantation.
• Metal-organic frameworks (MOFs) serve as effective drug delivery systems.
• Salidroside exhibits potent antioxidant and anti-inflammatory properties.

Purpose of the Study:

• To develop a hydrogel incorporating salidroside-loaded MOF nanoparticles (Hydrogel/MOFSP) for targeted delivery.
• To evaluate the efficacy of Hydrogel/MOFSP in mitigating myocardial IRI in post-transplant donor hearts.
• To elucidate the cardioprotective mechanism of Hydrogel/MOFSP.

Main Methods:

• Synthesized Hydrogel/MOFSP for sustained, cardiac-targeted salidroside release.
• Assessed in vitro antioxidant and anti-inflammatory properties of MOFSP and salidroside.
• Applied Hydrogel/MOFSP or salidroside to donor hearts post-reperfusion in a heterotopic transplantation model.
• Evaluated cardiac function, oxidative stress, inflammation, and apoptosis markers post-transplantation.

Main Results:

• Hydrogel/MOFSP application improved cardiac function compared to salidroside alone.
• Significantly reduced myocardial oxidative stress, inflammation, and apoptosis were observed in the Hydrogel/MOFSP group.
• Hydrogel/MOFSP mitigated IRI by downregulating the P38/mitogen-activated protein kinase (MAPK) signaling pathway.

Conclusions:

• Novel Hydrogel/MOFSP applied to post-transplant donor hearts enhances graft function and alleviates myocardial IRI.
• The cardioprotective effects are attributed to the downregulation of the P38/MAPK signaling pathway.
• This strategy offers a promising approach for improving outcomes in heart transplantation.