Background: Revascularization of
the heart after myocardial infarction (MI) using growth factors delivered by hydrogel-based microspheres represents a promising
therapeutic approach for cardiac regeneration. Microspheres have tuneable degradation properties and support
the prolonged release of soluble factors. Cardiac patches provide mechanical restraint, preventing dilatation associated with ventricular remodelling.
Methods: We combined
these approaches and produced a compacted calcium-alginate microsphere patch, restrained by a chitosan sheet, to deliver vascular endo
thelial growth factor (VEGF) to
the heart after myocardial injury in rats.
Results: Microspheres had an average diameter of 3.2 μm, were nonporous, and characterized by a smooth dimpled surface. Microsphere patches demonstrated prolonged
in vitro release characteristics compared to non-compacted microspheres and VEGF supernatants obtained from patches maintained
their bioactivity for
the 5 day duration of
the study
in vitro.
In vivo, patches were assessed with magnetic resonance imaging following MI, and demonstrated 50% degradation 25.6 days after implantation. Both VEGF
(−) and VEGF
(+) microsphere patch-treated hearts had better cardiac function than unpatched (chitosan sheet only) controls. However, VEGF
(+) microsphere-patched hearts had thicker scars characterized by higher capillary density in
the border zone than did those treated with VEGF
(−) patches. VEGF was detected in
the patches 4 weeks post-implantation.
Conclusion: The condensed microsphere patch represents a new
therapeutic platform for cytokine delivery and could be used as an adjuvant to current biomaterial and cell-based
therapies to promote localized angiogenesis in
the infarcted heart.
Statement of Significance
Following a heart attack, a lack of blood flow to the heart results in loss of heart cells. Growth factors may facilitate growth of blood vessels and heart tissue repair and prevent the onset of heart failure. Determining a way to deliver these growth factors directly to the heart is vital. Here, we combined two biomaterial-based approaches to deliver vascular endothelial growth factor (VEGF) to rat hearts after heart attack: a microsphere for prolonged release of VEGF, and a cardiac patch for mechanical restraint to prevent heart dysfunction. The feasibility of this microsphere patch was demonstrated by surgically implanting it over the infarct region of the heart post-injury. VEGF-patched hearts had better blood vessel growth, tissue repair, and heart function.