Recent Advances in Cardiac Tissue Engineering for the Management of Myocardium Infarction

Abstract

Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Recent studies on microfluidic devices employing stem cells under laboratory set-up have revealed meticulous events pertaining to the pathophysiology of MI occurring at the infarcted site. This discovery also underpins the appropriate conditions in the niche for differentiating stem cells into mature cardiomyocyte-like cells and leads to engineering of the scaffold via mimicking of native cardiac physiological conditions. However, the mode of stem cell-loaded engineered scaffolds delivered to the site of infarction is still a challenging mission, and yet to be translated to the clinical setting. In this review, we have elucidated the various strategies developed using a hydrogel-based system both as encapsulated stem cells and as biocompatible patches loaded with cells and applied at the site of infarction.

Keywords: biomaterial; cardiomyocytes; myocardial infarction; regeneration; stem cells; tissue engineering.

Figure 1

Schematic representation of various tissue engineering approaches for MI treatment. These approaches include hydrogel-based cell delivery (left hand corner), patch-based cell delivery (middle panel), and microfluidics-based drug screening (right corner) during the regenerative therapy of damaged heart tissue.

Figure 2

Illustration of stem cell-based regenerative medicine in MI treatment. Various stem cells like MSCs, ESCs, and iPSCs have been employed in MI treatment. Stem cells are delivered through engineered novel biomaterials (via encapsulation) that mimic the native niche. The stem cell-based regenerative therapy is beneficial to either replace the injured area or the whole organ.

Figure 3

Distinct cells of different origins which are used in the regenerative medicine depicted herein. Depending on the pluripotency, the transplanted cell types can differentiate into various other cells such as skeletal myoblasts, endothelial progenitor cells, chondrocytes, adipocytes, or cardiomyocytes.

Figure 4

Patch-based cell therapy development started with the fabrication of different patches made up of carbon nanostructures, conductive or non-conductive polymers, hydrogel, etc. followed by patch-based stem cell delivery for MI disease treatment.

Figure 5

Steps in microfluidic cardiac model generation—(a) Selection of cells and extracellular matrix are performed based on the physiology to be studied; (b) this is followed by design of the chip through different computational software to achieve the desired flow contours; (c) based on the design, the device is fabricated by various microfabrication procedures (the most common being photolithography; the steps of which are 1. spin coating of clean silicon wafer, 2. UV exposure with a mask, 3. dissolution of unwanted resist with developer solution to generate the master pattern, 4. PDMS mold creation from the master pattern, 5. punching of required inlet and outlet holes in the PDMS mold, and 6. bonding of the PDMS mold with a glass plate or another PDMS slab to close the device); (d) introduction of cell-laden hydrogel into the device for 3D culture (its selection is based on the mechanical properties needed for the micro tissue under study; (e) completion of the electrical circuit required for stimulation of the cardiac cells; (f) integration of the device with external circuitry and pumping mechanism for seamless operation of the chip [176,177,178,179].