Bioengineering the Infarcted Heart by Applying Bio-inspired Materials

Abstract

Induction of cardiac muscle regeneration following myocardial infarction (MI) represents a major challenge in cardiovascular therapy, as the current clinical approaches are limited in their ability to regenerate a new muscle tissue and to replace infarcted myocardium. Here, we describe the conception of two strategies based on bio-inspired materials, aimed at myocardial repair after MI. In the first strategy, alginate biomaterial was designed with affinity-binding moieties, enabling the binding of heparin-binding proteins and their controlled presentation and release. The combined features of this unique alginate hydrogel, as a temporary extracellular matrix replacement and a depot for bio-molecules such as insulin-like growth factor-1 and hepatocyte growth factor, led to improvements in cardiac structure and function, as demonstrated by the biomaterial's abilities to thicken the scar and prevent left-ventricular remodeling and dilatation. Endogenous regeneration occurring at the infarct as manifested by the enhanced angiogenesis, cardiomyocyte proliferation, and appearance of cardiac-related stem cells is likely to have contributed to this. In the second strategy, phosphatidylserine (PS)-presenting liposomes were developed to mimic apoptotic cells bodies, specifically their capability of immunomodulating activated macrophages into anti-inflammatory state. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging. The treatment promoted angiogenesis, the preservation of small scars, and prevention of ventricular dilatation and remodeling. Collectively, the two bio-inspired material-based strategies presented herein represent unique and clinical accessible approaches for myocardial infarct repair.

Factors Secreted by Mesenchymal Stem Cells and Endothelial Progenitor Cells Have Complementary Effects on Angiogenesis In Vitro

“…This hypothesis was confirmed by numerous studies showing that the CM, collected from a variety of stem cell populations, had beneficial effects on cells and tissues in vitro and in vivo [3,24]. These studies showed that various stem/ progenitor cell populations, such as MSCs or EPCs, released proangiogenic and antiapoptotic cytokines in culture, which may contribute to enhanced angiogenesis and endogenous repair [25]. However, for the stem cell-secreted factors to be useful in cell therapy for efficient vascular repair, more research is needed to identify the mechanisms by which they affect vasculogenesis.…”

Biomaterial‐Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives

“…that can bind and sequester growth factors (59) or contain fragments that influence cell recruitment (e.g. Fibrin fragment E is thought to contain angiogenic products).…”

Drug Carriers: Not an Innocent Delivery Man

“…5c) (68). These immunomodulatory effects of liposomes are now actively pursued as a way of increasing adjuvanicity of vaccines (69) or attenuating inflammation (70)(71)(72).…”