the cells to interact through cell signalling molecules and perform their physiological function. Thus, a tissue engineered cardiac construct must be designed to the
mimic ECM of the heart. Ideally, a scaffold for human cardiac tissue must have a
thickness of *0.5 cm with adequate porosity for oxygen transport and to allow a
cell density of *10
5 cells/cm
3 of the construct. The construct should also have the
ability to generate a force of 2–4 mN/mm
2 during contraction and to support
electrical signals propagation at *25 cm/s. It should also allow neovascularisation,
neuronal innervations and electromechanical cell coupling with the host myocardium upon transplantation into the host. An ideal biomaterial must be biocompatible and bio-mimetic yet biodegraddable in concomitant with the development of
new ECM after transplantation. It should also be amenable to laboratory procedures
for fabricating the scaffolds of desired physical, chemical and biological properties
and should be scalable of large-scale clinical applications. Some of the commercially available biomaterials for CTE are shown in Table 18.1.
Scaffolds for CTE have been developed using plant- or animal-derived natural
polymers such as alginate (Choe et al. 2019), chitosan (He et al. 2018), collagen
(Hosoyama et al. 2018), fibrin (Bagheri-Hosseinabadi et al. 2018), gelatin (Majidi
et al. 2018), hyaluronic acid (HA) (Hadisi et al. 2020), Poly (3-hydroxyoctanoate)
(Bagdadi et al. 2016) and glycosaminoglycan (Flanagan et al. 2006). Natural
polymer-derived scaffolds are generally biocompatible and biodegradable and
provide better cellular ECM-like environments to facilitate cell adhesion, proliferation and differentiation (Yi et al. 2017). Some polymers may be easily degraded
by body’s natural enzymes or have relatively weak mechanical properties, which
can be controlled by combing with synthetic polymers. The rate of degradation can
also be controlled by chemical cross-linking (Wu et al. 2014) of the biomaterials.
Some natural polymers have also been shown to have immunogenicity or may act
as a potential reservoir of infectious agents (Jawad et al. 2008). The later can
however, be controlled by use of genetically engineered and ‘immunologically
virgin’ animals reared under gnotobiotic conditions (Hwang et al. 2015).
18.3.1 Collagen I
Collage I is a predominant ECM protein of heart and is FDA approved for therapeutic use in skin and bone. It contains peptide sequences that interact with integrins to promote cell attachment. It can also modify the substrate stiffness and
thereby alter the cellular functions such as growth, proliferation and differentiation.
Thus, it has been used extensively in CTE as hydrogel, sponge-like scaffold or as
coating material for enhancing hydrophilicity of synthetic biomaterials. Electrospun
of sub-micron diameter fibrils of collagen has also been possible, which could be
rapidly and densely infiltrated by the cells and helped in the formation of functional
blood vessels (Telemeco et al. 2005). Hamdi et al. (2009) observed significant
increase in angiogenesis at the site of MI upon transplantation of myoblast-seeded
collagen scaffold. Similar results were also observed with bone marrow-derived
18 Cardiac Tissue Engineering: A Role for Natural Biomaterials
621
mimic ECM of the heart. Ideally, a scaffold for human cardiac tissue must have a
thickness of *0.5 cm with adequate porosity for oxygen transport and to allow a
cell density of *10
5 cells/cm
3 of the construct. The construct should also have the
ability to generate a force of 2–4 mN/mm
2 during contraction and to support
electrical signals propagation at *25 cm/s. It should also allow neovascularisation,
neuronal innervations and electromechanical cell coupling with the host myocardium upon transplantation into the host. An ideal biomaterial must be biocompatible and bio-mimetic yet biodegraddable in concomitant with the development of
new ECM after transplantation. It should also be amenable to laboratory procedures
for fabricating the scaffolds of desired physical, chemical and biological properties
and should be scalable of large-scale clinical applications. Some of the commercially available biomaterials for CTE are shown in Table 18.1.
Scaffolds for CTE have been developed using plant- or animal-derived natural
polymers such as alginate (Choe et al. 2019), chitosan (He et al. 2018), collagen
(Hosoyama et al. 2018), fibrin (Bagheri-Hosseinabadi et al. 2018), gelatin (Majidi
et al. 2018), hyaluronic acid (HA) (Hadisi et al. 2020), Poly (3-hydroxyoctanoate)
(Bagdadi et al. 2016) and glycosaminoglycan (Flanagan et al. 2006). Natural
polymer-derived scaffolds are generally biocompatible and biodegradable and
provide better cellular ECM-like environments to facilitate cell adhesion, proliferation and differentiation (Yi et al. 2017). Some polymers may be easily degraded
by body’s natural enzymes or have relatively weak mechanical properties, which
can be controlled by combing with synthetic polymers. The rate of degradation can
also be controlled by chemical cross-linking (Wu et al. 2014) of the biomaterials.
Some natural polymers have also been shown to have immunogenicity or may act
as a potential reservoir of infectious agents (Jawad et al. 2008). The later can
however, be controlled by use of genetically engineered and ‘immunologically
virgin’ animals reared under gnotobiotic conditions (Hwang et al. 2015).
18.3.1 Collagen I
Collage I is a predominant ECM protein of heart and is FDA approved for therapeutic use in skin and bone. It contains peptide sequences that interact with integrins to promote cell attachment. It can also modify the substrate stiffness and
thereby alter the cellular functions such as growth, proliferation and differentiation.
Thus, it has been used extensively in CTE as hydrogel, sponge-like scaffold or as
coating material for enhancing hydrophilicity of synthetic biomaterials. Electrospun
of sub-micron diameter fibrils of collagen has also been possible, which could be
rapidly and densely infiltrated by the cells and helped in the formation of functional
blood vessels (Telemeco et al. 2005). Hamdi et al. (2009) observed significant
increase in angiogenesis at the site of MI upon transplantation of myoblast-seeded
collagen scaffold. Similar results were also observed with bone marrow-derived
18 Cardiac Tissue Engineering: A Role for Natural Biomaterials
621