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Saxena et al. Mini-invasive Surg 2020;4:62 I http://dx.doi.org/10.20517/2574-1225.2020.68 Page 9 of 15

venules (10-100 μm), and veins (0.1 mm to > 1 cm). The optimized wt% for a balance in mechanical
strength and cytocompatibility was found to be 50% of PEGDA. All these studies have proven PEG as a
special candidate with highly tunable cell response, mechanical strength, bioactivity and cell functioning
as well. PEG can be tuned on the basis of its molecular weight, orientation and cross linking with other
materials as well. PEG is mostly blended with existing materials such as PCL to synergistically enhance the
desired properties for PCI in the treatment of MI.

ECM HYDROGELS IN CARDIAC TISSUE REPAIR
The cardiac ECM is made up of three major components, namely glycoproteins, proteoglycans, and
glycosaminoglycans. Various glycoproteins such as fibronectin, laminin, fiber proteins, and prototypical
matricellular proteins enrich the cardiac ECM. The major protein in cardiac ECM is fibrillar collagen. In
mammalian hearts, cardiomyocyte proliferation may occur in neonates at a cardiac injury, but in adults,
[49]
regeneration capacity is absent . Cardiac ECM has a prominent effect in cardiac repair and regeneration,
[50]

and changes vigorously after MI , yet the mechanical stiffness of free ECM is a major challenge in its
use for PCI. Various approaches have been developed on the basis of ECM being used directly as the
biomaterial for the cardiac tissue repair. ECM molecules are isolated and utilized directly as injectable
hydrogels by intramyocardial injection or intracoronary perfusions. In these approaches, the injectable
materials were supplemented with various materials such as DNA/RNA and cell active factors along with
cardiac cells and growth factors as well, as shown in Figure 6, which synergistically helped in the repair of
[51]
the cardiac tissues .
[52]
In a recent study, Du et al. investigated the role of 5A/6A promoter polymorphism in the matrix
metalloproteinase 3 (MMP-3) gene and in-stent restenosis (ISR). An increment in the ISRs with genotype
proportion of 6A6A and a decrement in the 5A allele were reported. The findings suggested the role of
gene-based cell proliferation in ISRs, hinting at the role of ECM interaction with the stents in cardiac tissue
[53]
repair. Similarly, MMP-2 and -9 also play an important role in acute MI and cardiac tissue repair . Hence,
addition/delivery of these proteins may play a pivotal role in designing PCI with effective cardiac tissue
[54]
repair. Growth factor impregnated nanomaterials play a vital role in CTE. In this direction, Mewhort et al.
proposed a surgical procedure using a CorMatrix-ECM biomaterial patch for the treatment of ischemic
heart failure. The electrocardiography revealed an increment in the ejection fraction of basic fibroblasts,
and prevention of left ventricle remodeling. The improvement in left ventricle contractility was confirmed
by the pressure volume loop analysis. Various other factors such as coating of ECM and its biodegradation
[55]
have also been tested for the improved healing/repair of the damaged cardiac tissue. In this regard, Liu et al.
performed the nanocoating of ECM-Inspired SDF-1α/Laminin for cardiac wound healing on the 316L
stainless steel surface, as shown in Figure 7. It was found that the biomolecules were delivered in a
controlled way at the site of action, and a promising approach was established to repair the cells after the
injury. In addition, the designed layer inhibited platelet adhesion and activation, leading to controlled or
reduced thrombosis and clot generation. The designed layer also enhanced endothelial cell migration and
endothelial progenitor cell aggregation, resulting in faster cardiac tissue repair. All these studies showed
that the incorporation of ECM and its constituents significantly affected the cellular repair and has a
promising future if clubbed with PCI in the treatment of MI.

CHALLENGES AND FUTURE PERSPECTIVES
Various approaches have been applied in the treatment of MI using hydrogels with a varied degree
of success. These approaches have been individually focusing on various factors such as mechanical
strength, reduced thrombosis, tissue repair and cell regeneration. However, very few approaches have been
attempted to incorporate all the desired properties in single stents to be used for PCI in the treatment
of MI. Additionally, the hydrogels for PCI possessed major challenges in their mechanical strength,