Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction

Area of Science:

• Biomaterials science
• Regenerative medicine
• Cardiovascular research

Background:

• Injectable scaffolds are crucial for cardiac tissue regeneration after myocardial infarction (MI).
• Existing natural biomaterial gels often lack the mechanical strength for long-term cardiac support.
• Decellularized cardiac extracellular matrix (ECM) offers bioactivity but requires mechanical enhancement.

Purpose of the Study:

• To develop novel injectable scaffolds based on decellularized porcine cardiac ECM (pcECM) with improved mechanical properties.
• To evaluate the biocompatibility, bioactivity, and therapeutic efficacy of these pcECM-based gels in MI rat models.
• To assess the potential for cardiac function preservation and improvement following scaffold implantation.

Main Methods:

• Solubilized pcECM was cross-linked with genipin and engineered with chitosan.
• Scaffolds were characterized for mechanical properties and biocompatibility in vitro with mesenchymal stem cells.
• In vivo studies involved injecting scaffolds into rat hearts post-MI (acute and chronic models).
• Cardiac function was assessed using echocardiography and hemodynamics; tissue remodeling and cell infiltration were analyzed.

Main Results:

• The developed pcECM-based gels exhibited tunable mechanical properties.
• Mesenchymal stem cells showed high viability, remodeling, and supported cell organization within the gels.
• The scaffolds demonstrated no in vitro or in vivo immunogenicity.
• Treatment with pcECM gels significantly preserved and improved cardiac function up to 12 weeks post-MI in rat models.
• Scaffolds promoted progenitor cell infiltration, suggesting biological remodeling capabilities.

Conclusions:

• Injectable pcECM-based scaffolds offer a promising therapeutic strategy for cardiac tissue regeneration post-MI.
• These biohybrid materials overcome the mechanical limitations of natural ECM while retaining its bioactivity.
• The scaffolds demonstrate significant potential for restoring and enhancing cardiac function in both acute and chronic MI models.