formation can be done by various methods such as temperature modulation,
enzymatic activation, alteration of pH, or ionic cross-linkage. Unlike porous or
fibrous scaffolds, the shape, stiffness and thickness of cell-encapsulated hydrogels
can be easily controlled and therefore, they can be directly injected into the heart
tissue in vivo as in situ construct (Ye and Black 2011). A major limitation in the use
of hydrogels for CTE is its inherent heterogeneous nature which can influence
mechanical properties of the construct and may result in graft failure due to
improper mechanical and electrical integration into recipient myocardium.
18.7.4 Bio-Fabricated/Micro-Fabricated Scaffolds
In recent years, need for microfabrication of scaffolds has been felt to mimic the
natural structure of the heart. Mammalian heart has unique and intricate structural
organization such as parallel aligned myocytes and myofibers which varies along
the depth of the ventricular wall. These topological cues and structural anisotropy of
heart are important for CTE and therefore, strategies such as nanopatterning of
biomaterials, stamping of ECM proteins on scaffolds, 3D tissue printing,
textile-templated scaffolds etc. have been attempted as novel means to mimic native
ECM and enhance functionality of cardiac tissue construct (Zhang et al. 2019).
Thomson et al. microtemplated fibrin scaffolds with uniform architecture of parallel
microchannels (60 lm), surrounded by an interconnected microporous network of
pores (27 lm) and mechanical stiffness (70–90 kPa) comparable to native cardiac
tissues (Thomson et al. 2013). Tri-culture of CMs, EC and fibroblasts on
microtemplated fibrin scaffolds mimicked native cardiac tissue in structure and
cellular composition.
Natural biomaterials have also been used as bioink to develop scaffolds of
pre-defined and organized architecture by 3D tissue printing or prototyping. The 3D
bioprinting allows the deposition of cells, biomaterials and signalling molecules
into precisely organized geometrics and therefore, helps in biofabrication of tissue
constructs similar to those found in the native heart (Alonzo et al. 2019). A number
of bioprinting technology including extrusion, inkjet, laser-assisted and stereolithography with natural as well as synthetic bioinks have been developed and
applied to the CTE. Gaetani et al. (2012) successfully used tissue printing technology to fabricate scaffold for culturing human cardiac progenitor cells. In yet
another methodology, using knitted conventional textiles made of cotton or
polyester yarns as template targets. Hong et al. (2020) used digital lighting processing printer for 3D printing of silk fibroin natural polymer with
gycidyl-methacrylate as bioink. Silk fibroin was also combined with Collagen I for
3D printing and development of cardiac patches after seeding with MSC
(Sanz-Fraile et al. 2020). Mixture of different cells with hydrogels have been
printed for functional vascularized patches with the help 3D printing that meets
immunological and anatomical properties of native heart tissue (Noor et al. 2019).
18 Cardiac Tissue Engineering: A Role for Natural Biomaterials
633
enzymatic activation, alteration of pH, or ionic cross-linkage. Unlike porous or
fibrous scaffolds, the shape, stiffness and thickness of cell-encapsulated hydrogels
can be easily controlled and therefore, they can be directly injected into the heart
tissue in vivo as in situ construct (Ye and Black 2011). A major limitation in the use
of hydrogels for CTE is its inherent heterogeneous nature which can influence
mechanical properties of the construct and may result in graft failure due to
improper mechanical and electrical integration into recipient myocardium.
18.7.4 Bio-Fabricated/Micro-Fabricated Scaffolds
In recent years, need for microfabrication of scaffolds has been felt to mimic the
natural structure of the heart. Mammalian heart has unique and intricate structural
organization such as parallel aligned myocytes and myofibers which varies along
the depth of the ventricular wall. These topological cues and structural anisotropy of
heart are important for CTE and therefore, strategies such as nanopatterning of
biomaterials, stamping of ECM proteins on scaffolds, 3D tissue printing,
textile-templated scaffolds etc. have been attempted as novel means to mimic native
ECM and enhance functionality of cardiac tissue construct (Zhang et al. 2019).
Thomson et al. microtemplated fibrin scaffolds with uniform architecture of parallel
microchannels (60 lm), surrounded by an interconnected microporous network of
pores (27 lm) and mechanical stiffness (70–90 kPa) comparable to native cardiac
tissues (Thomson et al. 2013). Tri-culture of CMs, EC and fibroblasts on
microtemplated fibrin scaffolds mimicked native cardiac tissue in structure and
cellular composition.
Natural biomaterials have also been used as bioink to develop scaffolds of
pre-defined and organized architecture by 3D tissue printing or prototyping. The 3D
bioprinting allows the deposition of cells, biomaterials and signalling molecules
into precisely organized geometrics and therefore, helps in biofabrication of tissue
constructs similar to those found in the native heart (Alonzo et al. 2019). A number
of bioprinting technology including extrusion, inkjet, laser-assisted and stereolithography with natural as well as synthetic bioinks have been developed and
applied to the CTE. Gaetani et al. (2012) successfully used tissue printing technology to fabricate scaffold for culturing human cardiac progenitor cells. In yet
another methodology, using knitted conventional textiles made of cotton or
polyester yarns as template targets. Hong et al. (2020) used digital lighting processing printer for 3D printing of silk fibroin natural polymer with
gycidyl-methacrylate as bioink. Silk fibroin was also combined with Collagen I for
3D printing and development of cardiac patches after seeding with MSC
(Sanz-Fraile et al. 2020). Mixture of different cells with hydrogels have been
printed for functional vascularized patches with the help 3D printing that meets
immunological and anatomical properties of native heart tissue (Noor et al. 2019).
18 Cardiac Tissue Engineering: A Role for Natural Biomaterials
633