Injectable myocardium-derived hydrogels with SDF-1α releasing for cardiac repair

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Cardiovascular Research

Background:

• Myocardial infarction (MI) is a leading cause of death worldwide, with current treatments often failing to address profibrotic remodeling.
• Therapeutic chemokines like stromal cell-derived factor 1α (SDF-1α) show promise for MI treatment, but effective delivery remains a challenge.
• Previous attempts using direct injection or simple hydrogel entrapment of SDF-1α yielded limited therapeutic benefits.

Purpose of the Study:

• To develop and evaluate a novel sustained-release system for SDF-1α delivery to treat post-MI cardiac remodeling.
• To create a nanocomposite hydrogel combining SDF-1α-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) with cardiac decellularized extracellular matrix (cdECM).
• To assess the system's efficacy in improving mechanical properties, cell compatibility, SDF-1α bioactivity, angiogenesis, and cardiac function post-MI.

Main Methods:

• Fabrication of an injectable hydrogel system using SDF-1α-loaded PLGA NPs within a porcine cdECM matrix.
• In vitro assessment of SDF-1α release kinetics over four weeks and cell compatibility with H9C2 cells.
• Evaluation of SDF-1α bioactivity through in vitro chemotaxis assays.
• In vivo studies involving intramyocardial injection into infarcted rat hearts to assess angiogenesis and cardiac function.

Main Results:

• The PLGA NP-cdECM hydrogel demonstrated sustained SDF-1α release for four weeks, significantly longer than direct encapsulation.
• Incorporation of PLGA NPs improved hydrogel mechanical properties, increasing Young's modulus and compressive strength.
• The nanocomposite hydrogel exhibited good cell compatibility and preserved SDF-1α bioactivity, promoting cell migration.
• In vivo studies showed enhanced angiogenesis and improved cardiac function in the infarcted area following intramyocardial injection.

Conclusions:

• The developed SDF-1α-loaded PLGA NP-cdECM nanocomposite hydrogel offers a promising sustained-release strategy for myocardial infarction treatment.
• This system effectively enhances cardiac tissue repair by promoting angiogenesis and improving cardiac function.
• Combining localized, sustained chemokine delivery with advanced biomaterials represents a viable therapeutic approach for cardiovascular diseases.