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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 5 of 15

to the treatment of the cardiac tissues. A 3D porous network with pore size of 20 ± 3 μm and 32 ± 5 μm was
respectively obtained for CS/CG and GQDs-CS/CG hydrogels. The designed hydrogel possessed enhanced
cell survival rate and pro-angiogenic factors, making it suitable for CTE to treat acute MI. Both studies
suggest that the addition of chitosan creates a stent free from various cellular and enzymatic rejection
problems and rapid degradation, leading to a suitable stent-based angioplasty after acute MI.

Various other studies have been conducted using chitosan as hydrogel material for PCI. Chitosan, being
highly bioactive, biocompatible and moderately biodegradable, has also been used as a coating material on
[35]
[36]
various stents for the treatment of MI . In such an approach, Lin et al. coated polyvinyl alcohol (PVA)
fibers with chitosan using the spray coating method, without sealing the meshes. PVA fibers were fashioned
into braids using 16-spindle braider and cross-linked with glutaraldehyde to stabilize the interlacing
points followed by spray coating with chitosan. Mesh sizes ranging from 0.20-0.35 mm with a membrane
2
thickness of 0.27-0.41 μm were obtained. Chitosan coating was reported to improve compression
resistance. It was found that the chitosan-coated PVA stents were suitable for use in PCI because of their
higher bioactivity and cytocompatibility (80% cell viability).

A blending approach has also been attempted to enhance the biocompatibility as well as the biodegradation
of the stent material. In a recent study, poly-lactic acid/chitosan nanofibers were electrospun and loaded
with paclitaxel as a coating material for the prototype polymeric stent. A single-nozzle electrospinning
approach was utilized to make the fibrous stent. The chitosan concentration was varied from 3-9 wt%,
and the drug loading concentration wt was varied from 40-120 wt% to obtain an optimum composite
fiber. The physical encapsulation of the drug in the polymeric matrix without any chemical bonding
was reported. The samples with the 40% and 60% drug loading displayed controlled drug release. An
increase in chitosan concentration provided more homogenous fibers with smaller mean diameter, yet
agglomeration was observed after 5% chitosan. Excellent cell viability (> 90%) was observed up to 60%
drug loading. However, a further increase in the drug concentration resulted in decreased cell viability. The
[37]
cell viability was decreased to 50% at a drug concentration 80% due to the exceeding the cytotoxic limit .
Hence, these findings suggested that chitosan-containing stents are very effective for use in stents for PCI.

ALGINATE-BASED HYDROGELS FOR PCI
Alginate, a natural polymer, has also been studied as a potential material for cardiac stents in the treatment
of MI. Alginate possesses moderate cross-linking properties demonstrating it as a suitable candidate
for stent preparation. Alginates are linear copolymers and are mostly composed of (1-4)-linked α-L-
guluronic (G) and β-D-mannuronic (M) residues as shown in Figure 3. The number of sequences depends
on the isolation species, i.e., the organisms and tissues. The random sequences of these G and M residues
intercalate to form the alternating region of the MG blocks. The rigid 6-membered sugar rings add the
restricted rotation around the glycosidic linkage and provide stiffness to the alginate . This indicates
[38]
its suitability for stent applications, as stiffness similar to that of the artery is a required property of stent
material for proper blood flow, restriction from mechanical damage and degradation.

Alginate has been utilized for various biomedical applications because of its gelling properties and natural
origin. Cross-linking is usually done by the diffusion method using Ca(II) or Na(I) ions making the
[39]
polymer stiffer . The inherent pre-requisite of cross-linking for the gel formation by alginate monomer
makes it more effective and provides the competence to tune the stiffness for various applications. In
addition, high mechanical and chemical stability, adequate swelling properties, narrow pore size distribution
[40]
and pore size make alginate a strong candidate for stent formation. However, its poor bioactivity and
biocompatibility, as well as its stiffness equivalent to the surrounding tissues, need to be explored prior to
its application. Various approaches have been explored to use alginate as stent material for the treatment
of MI using PCI. Recently, You et al. prepared an alginate dialdehyde-gelatin hydrogel bio-ink for 3D
[22]