Nanotechnology and Cardiovascular Tissue Engineering - Stem-Cell Nanoengineering - page 275

approach to nanofiber fabrication that relies on weak noncovalent interactions to build
nanofibers from small molecules, proteins, peptides, and nucleic acids [43]. This approach
could be used to assemble the nanofibers in vivo to create an injectable scaffold for tissue
repair. Further details about these methods have been reported elsewhere [44].
Nanoscaffolds and Cardiovascular Tissue Engineering
Various types of fibers have been developed as nanoscaffolds that act as biomimetic cardiac
patches to support the growth of cardiomyocytes. These nanofibrous scaffolds have an
elastic modulus of a magnitude nearing that of native heart tissue in cardiac tissue engi-
neering. Among electrospun fibers, a composite nanofibrous scaffold of poly( d , l -lactide-
co-glycolide)/gelatin (PLGA/Gel) has been fabricated and it has been shown that the isolated
cardiomyocytes seeded on PLGA/Gel nanofibers express the typical functional cardiac
proteins such as alpha-actinin and troponin [45]. Poly( d , l -lactide-co-glycolic) is one of the
most commonly used biodegradable, biocompatible materials. A scaffold, comprising of
carbon nanofibers (CNF) embedded in PLGA has been shown to promote cardiomyocyte
growth compared with conventional polymer substrates, because they mimic native heart
tissue tensile strength/conductivity and increase the adsorption of proteins known to
promote cardiomyocyte function [46]. Another scaffold based on short poly(glycerol
sebacate) fibers has been developed by Ravichandran et al. [47]. The cardiac marker proteins
actinin, troponin, myosin heavy chain and connexin 43 express more on short poly(glycerol
sebacate) fibers compared to PLLA nanofibers [47]. Another biocompatible and elastomeric
nanofibrous scaffold electrospun from a blend of poly(1,8-octanediol-co-citrate) [POC] and
PLLA-co-poly-(3-caprolactone) [PLCL] has been produced for application as a bioengi-
neered patch for cardiac tissue engineering. The proliferation of cardiac myoblast cells on
the electrospun POC/PLCL scaffolds is found to increase from days 2 to 8, with the increasing
concentration of POC in the composite. The morphology and cytoskeletal observation of
the cells also demonstrate the biocompatibility of the POC-containing scaffolds. Electrospun
POC/PLCL4060 nanofibers are promising elastomeric substrates that might provide the
necessary mechanical cues to cardiac muscle cells for regeneration of the heart [48].
Composites of collagen and electrospun poly(glycolic acid) (PGA) fibers have also been
shown to promote the attachment and proliferation of cardiac stem cells, which have a great
potential to differentiate into cardiomyocytes [49]. Recently, Hussain et al . (2012) have
fabricated bioactive three-dimensional chitosan nanofiber scaffolds using the electros-
pinning technique and explored its potential for long-term cardiac function in the
three-dimensional co-culture model [50]. Chitosan is a natural polysaccharide biomaterial
that is biocompatible, biodegradable, nontoxic, and cost effective. The chitosan fibers were
coated with fibronectin via adsorption in order to enhance cellular adhesion to the fibers
and migration into the interfibrous milieu. Ventricular cardiomyocytes from neonatal rats
and fibroblasts were seeded onto the coated scaffolds and the results demonstrated that
cardiomyocyte-fibroblast co-cultures result in polarized cardiomyocyte morphology, and
they also retain their morphology and function for long-term culture [50]. Smith et al. (2012)
fabricated polyethylene glycol (PEG) microsphere scaffolds in the presence of dextran by a
phase-separation method and showed that the scaffold can support the long-term
three-dimensional culture of cardiomyocytes by enhancing their viability and expression of
cardiac protein markers [51]. In another excellent study, Kim et al. (2010) report construction
of a scalable nanotopographically controlled model of myocardium mimicking the in vivo
ventricular organization. The produced myocardium comprises of an anisotropically
nanofabricated substratum formed from scalable, biocompatible polyethylene glycol (PEG)
hydrogel arrays. The nanofabricated substrate provides appropriate cues to the seeded