18.4 Enhancing the Elasticity and Electrical Conductivity
of Natural Biomaterials for CTE
Polymeric scaffolds for CTE must exhibit elasticity and high electrical conductivity
to mimic the flexibility, electrical conductance, and contractility of native cardiac
tissues (Ye et al. 2020). Many of biomaterials currently used in CTE lack of
electrical conductivity and appropriate mechanical properties. This can be overcome by use of hybrid biomaterials combining two or more natural and synthetic
biomaterials or combining with conductive nanomaterials. For examples, natural
polymers such as chitosan have low elastic modulus and poor electrical conductivity, which could be improved by doping with carbon nanofibers to develop a
highly conductive composite scaffold (Martins et al. 2014). Chitosan/carbon
composite scaffolds had an elastic modulus of 28.1 ± 3.3 kPa, similar to that
measured for rat myocardium, and excellent electrical properties, with a conductivity of 0.25 ± 0.09 S/m (Martins et al. 2014). Similarly, incorporation of carbon
nanohorns into collagen was reported to promote the proliferation of rat CMs and
inhibit the proliferation of cardiac fibroblasts (Wu et al. 2016).
Metallic nanoparticles such as Au-NPs have also been combined with natural
polymers to develop thermosensitive and/or electro-conductive scaffolds (Min et al.
2018). Baei et al. (2016) developed a thermosensitive conductive hydrogel with a
highly porous network of interconnected pores by incorporating nanoscale
electro-conductive Au-NPs into chitosan hydrogels. AuNP-collagen matrix with
localized nanoscale stiffness in the substrate activated the b1-integrin signalling,
which mediates the activation of integrin-linked kinase and its downstream signal
kinase for cardiac cell differentiation (Li et al. 2016). Sapir et al. (2014a) created a
functional cardiac patch by incorporating magnetically responsive nanoparticles
into macroporous alginate scaffold and applying external magnetic stimulation. In
recent years, incorporation of reduced graphene oxide (rGO) into biomaterials has
also attracted great attention. Shin et al. engineered cardiac constructs using
rGO-incorporated gelatin methacryloyl (GelMA) hybrid hydrogels (Shin et al.
2016). The incorporation of rGO into the GelMA matrix significantly enhanced
electrical conductivity and mechanical properties of material and exhibited better
viability, proliferation, and maturation of CMs compared to those cultured on
GelMA hydrogels. Similarly, Jiang et al. (2019) developed electroconductive
porous scaffold of chitosan for CTE by blending with GO. Incorporation of GO into
chitosan resulted in an electro-conductivity of 0.134 S/m, which is in the range of
conductivity required for native heart tissue. Combination of natural biomaterials
with synthetic biomaterials has also been tried. Bhaarathy et al. used copolymer of
poly (l-lactic acid)-co-poly (e-caprolactone) (PLACL), silk fibroin and Aloe Vera
for fabricating biocomposite nanofibrous scaffolds for CTE (Bhaarathy et al. 2014).
18 Cardiac Tissue Engineering: A Role for Natural Biomaterials
629
of Natural Biomaterials for CTE
Polymeric scaffolds for CTE must exhibit elasticity and high electrical conductivity
to mimic the flexibility, electrical conductance, and contractility of native cardiac
tissues (Ye et al. 2020). Many of biomaterials currently used in CTE lack of
electrical conductivity and appropriate mechanical properties. This can be overcome by use of hybrid biomaterials combining two or more natural and synthetic
biomaterials or combining with conductive nanomaterials. For examples, natural
polymers such as chitosan have low elastic modulus and poor electrical conductivity, which could be improved by doping with carbon nanofibers to develop a
highly conductive composite scaffold (Martins et al. 2014). Chitosan/carbon
composite scaffolds had an elastic modulus of 28.1 ± 3.3 kPa, similar to that
measured for rat myocardium, and excellent electrical properties, with a conductivity of 0.25 ± 0.09 S/m (Martins et al. 2014). Similarly, incorporation of carbon
nanohorns into collagen was reported to promote the proliferation of rat CMs and
inhibit the proliferation of cardiac fibroblasts (Wu et al. 2016).
Metallic nanoparticles such as Au-NPs have also been combined with natural
polymers to develop thermosensitive and/or electro-conductive scaffolds (Min et al.
2018). Baei et al. (2016) developed a thermosensitive conductive hydrogel with a
highly porous network of interconnected pores by incorporating nanoscale
electro-conductive Au-NPs into chitosan hydrogels. AuNP-collagen matrix with
localized nanoscale stiffness in the substrate activated the b1-integrin signalling,
which mediates the activation of integrin-linked kinase and its downstream signal
kinase for cardiac cell differentiation (Li et al. 2016). Sapir et al. (2014a) created a
functional cardiac patch by incorporating magnetically responsive nanoparticles
into macroporous alginate scaffold and applying external magnetic stimulation. In
recent years, incorporation of reduced graphene oxide (rGO) into biomaterials has
also attracted great attention. Shin et al. engineered cardiac constructs using
rGO-incorporated gelatin methacryloyl (GelMA) hybrid hydrogels (Shin et al.
2016). The incorporation of rGO into the GelMA matrix significantly enhanced
electrical conductivity and mechanical properties of material and exhibited better
viability, proliferation, and maturation of CMs compared to those cultured on
GelMA hydrogels. Similarly, Jiang et al. (2019) developed electroconductive
porous scaffold of chitosan for CTE by blending with GO. Incorporation of GO into
chitosan resulted in an electro-conductivity of 0.134 S/m, which is in the range of
conductivity required for native heart tissue. Combination of natural biomaterials
with synthetic biomaterials has also been tried. Bhaarathy et al. used copolymer of
poly (l-lactic acid)-co-poly (e-caprolactone) (PLACL), silk fibroin and Aloe Vera
for fabricating biocomposite nanofibrous scaffolds for CTE (Bhaarathy et al. 2014).
18 Cardiac Tissue Engineering: A Role for Natural Biomaterials
629