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

Ischemia-reperfusion injury (IRI) is a leading cause of primary graft dysfunction in heart transplantation. Metal-organic frameworks (MOFs) are widely applied as drug delivery carriers. Salidroside has been recognized for its potent anti-oxidative and anti-inflammatory effects. In this study, we developed the hydrogel incorporating salidroside-loaded MOF nanoparticles (Hydrogel/MOFSP) and applied it to the surface of post-transplant donor hearts to alleviate myocardial IRI.

Hydrogel/MOFSP was synthesized to facilitate sustained and cardiac-targeted drug release for salidroside. We evaluated MOFSP nanoparticles or salidroside's anti-oxidative and anti-inflammatory properties in vitro. Furthermore, donor hearts were heterotopically transplanted after 3-hour cold storage with PBS (vehicle group), or salidroside or Hydrogel/MOFSP applied to the surface of donor hearts immediately after in vivo reperfusion. We investigated the cardiac function and the levels of oxidative stress, inflammation, and apoptosis of donor hearts after 6-hour heart transplantation and the mechanism of the cardioprotective effect of Hydrogel/MOFSP.

MOFSP nanoparticles or salidroside displayed anti-oxidative and anti-inflammatory properties in vitro, whereas applying Hydrogel/MOFSP rather than only salidroside to the surface of post-transplant grafts could improve cardiac function. Significantly reduced levels of myocardial oxidative stress, inflammation, and apoptosis were observed in the Hydrogel/MOFSP group. Hydrogel/MOFSP mitigated myocardial IRI for post-transplant grafts through the downregulation of P38/mitogen-activated protein kinase (MAPK) signaling pathway.

Applying novel Hydrogel/MOFSP to the surface of post-transplant donor hearts improved graft function and alleviated myocardial IRI in heart transplantation. The cardioprotective effects of Hydrogel/MOFSP were achieved through the downregulation of the P38/MAPK signaling pathway.