A Sr2+-Incorporated Polysaccharide Hydrogel Promotes Multifunctional Cardiac Repair after Myocardial Infarction

Area of Science:

• Biomaterials Science
• Cardiovascular Research
• Regenerative Medicine

Background:

• Myocardial infarction (MI) causes adverse ventricular remodeling, leading to progressive cardiac dysfunction due to impaired angiogenesis, cardiomyocyte loss, and fibrosis.
• Current therapeutic strategies often involve complex multi-component approaches.
• There is a need for innovative biomaterials that can deliver therapeutic cues to promote cardiac repair.

Purpose of the Study:

• To develop and evaluate a thermosensitive, injectable strontium-loaded hydrogel (Sr@OSDA) for myocardial repair post-MI.
• To investigate the effects of Sr@OSDA on angiogenesis, cardiac remodeling, and macrophage response in a rat MI model.
• To assess the potential of Sr@OSDA as a simplified therapeutic design harnessing the bioactivities of strontium ions (Sr2+).

Main Methods:

• Fabrication of a thermosensitive injectable Sr2+-loaded OSA-DTPH-agarose hydrogel (Sr@OSDA) using dynamic Schiff-base crosslinking, agarose physical networking, and reversible Sr2+-carboxylate coordination.
• Characterization of hydrogel biocompatibility and mechanical properties.
• In vivo evaluation in a rat MI model to assess angiogenesis, cardiac function, and ventricular remodeling.

Main Results:

• Sr@OSDA demonstrated favorable biocompatibility and mechanical properties similar to native myocardium.
• The hydrogel facilitated sustained local Sr2+ availability in the infarct microenvironment.
• In vivo studies showed Sr@OSDA significantly promoted angiogenesis via AKT/eNOS pathway activation, increased microvessel density (CD31+), and arteriole formation (α-SMA+).
• Sr@OSDA enhanced reparative macrophage responses, modulated early-stage autophagic activity, and partially restored connexin 43 (Cx43) expression.
• These effects led to improved myocardial repair and attenuated adverse ventricular remodeling post-MI.

Conclusions:

• Sr@OSDA is a mechanically adaptive hydrogel platform capable of delivering bioactive Sr2+ for ischemic myocardial repair.
• The hydrogel promotes angiogenesis and modulates cellular responses, contributing to improved cardiac function and reduced adverse remodeling after MI.
• Sr@OSDA offers a simplified, effective therapeutic strategy for myocardial regeneration by leveraging the pleiotropic effects of Sr2+.