18.3.7 Decellularized ECM
Decellularized ECM of heart (Singelyn et al. 2009), and other organs such as small
intestinal submucosa (SIS) (Crapo and Wang 2010), and urinary bladder (Robinson
et al. 2005) has also been incorporated into scaffolds for CTE. Decellularization of
tissues by detergents such as SDS can remove cells without affecting the biochemical composition and mechanical properties of the ECM in terms of elasticity,
strength and durability (Eitan et al. 2010). The viscoelasticity and strength of the
decelluralized cardiac ECM was reported to be similar to those of native tissue,
although its elasticity and apparent viscosity are higher (Bronshtein et al. 2013).
Seeding and culturing of decelluralized cardiac tissue with MSCs partially restored
the mechanical properties lost after decellularization (Bronshtein et al. 2013). Thus,
decellularized ECM of heart are being extensively explored as a natural biomaterial
for CTE and variable factors such efficient methods of ECM removal, homogeneous re-cellularization strategies and tailoring of ECM for enhancing bioactivity
(Kc et al. 2019).
Decellularized ECM has also been used in combination with other natural and
synthetic biomaterials. Stoppel et al. developed a silk-based scaffold containing
decellularized ECM of heart (Stoppel et al. 2015). These silk-ECM composite
scaffolds had tunable architectures, degradation rates, and mechanical properties
and their subcutaneous implantation in rats resulted in remarkable endogenous
cell infiltration and vascularization after 4 weeks in vivo. In vitro, silk-cECM
scaffolds maintained both the atrial CMs and the human ESC-derived CMs (Stoppel
et al. 2015).
Interestingly, xenogenic ECMs were also shown to be beneficial in promoting
human CM proliferation (Sarig et al. 2015). Crapo and Wang (2010) combined rat
CMs with pig SIS gel and cultured on porous elastomeric PCS scaffolds. They
observed that cardiac tissue engineered from pig SIS gel had a more physiological
rate of contraction than those produced on Matrigel™. However, the composition
of ECM varies from batch to batch and chances of immunogenicity and zoonosis
with xenogeneic sources of ECM cannot be ruled out.
18.3.8 Other Natural Biomaterials
Other natural biomaterials such as glycosaminoglycans, hyaluronic acid, Poly
(3-hydroxyoctanoate) etc. have also been used in CTE. Glycosaminoglycans are the
most abundant polysaccharide present in the body in the form of long unbranched
disaccharide units, where units contain either of two such as N-acetylgalactosamine
or N-acetylglucosamine and a uronic acid such as glucuronate or iduronate.
Hyaluronic acid is a macromolecule made of linear glycosaminoglycans and has been
reported to improve neovascularization of tissues and normalize the left ventricular
function in infracted rat hearts (Ventura et al. 2007). Poly (3-hydroxyoctanoate), Poly
18 Cardiac Tissue Engineering: A Role for Natural Biomaterials
627
Decellularized ECM of heart (Singelyn et al. 2009), and other organs such as small
intestinal submucosa (SIS) (Crapo and Wang 2010), and urinary bladder (Robinson
et al. 2005) has also been incorporated into scaffolds for CTE. Decellularization of
tissues by detergents such as SDS can remove cells without affecting the biochemical composition and mechanical properties of the ECM in terms of elasticity,
strength and durability (Eitan et al. 2010). The viscoelasticity and strength of the
decelluralized cardiac ECM was reported to be similar to those of native tissue,
although its elasticity and apparent viscosity are higher (Bronshtein et al. 2013).
Seeding and culturing of decelluralized cardiac tissue with MSCs partially restored
the mechanical properties lost after decellularization (Bronshtein et al. 2013). Thus,
decellularized ECM of heart are being extensively explored as a natural biomaterial
for CTE and variable factors such efficient methods of ECM removal, homogeneous re-cellularization strategies and tailoring of ECM for enhancing bioactivity
(Kc et al. 2019).
Decellularized ECM has also been used in combination with other natural and
synthetic biomaterials. Stoppel et al. developed a silk-based scaffold containing
decellularized ECM of heart (Stoppel et al. 2015). These silk-ECM composite
scaffolds had tunable architectures, degradation rates, and mechanical properties
and their subcutaneous implantation in rats resulted in remarkable endogenous
cell infiltration and vascularization after 4 weeks in vivo. In vitro, silk-cECM
scaffolds maintained both the atrial CMs and the human ESC-derived CMs (Stoppel
et al. 2015).
Interestingly, xenogenic ECMs were also shown to be beneficial in promoting
human CM proliferation (Sarig et al. 2015). Crapo and Wang (2010) combined rat
CMs with pig SIS gel and cultured on porous elastomeric PCS scaffolds. They
observed that cardiac tissue engineered from pig SIS gel had a more physiological
rate of contraction than those produced on Matrigel™. However, the composition
of ECM varies from batch to batch and chances of immunogenicity and zoonosis
with xenogeneic sources of ECM cannot be ruled out.
18.3.8 Other Natural Biomaterials
Other natural biomaterials such as glycosaminoglycans, hyaluronic acid, Poly
(3-hydroxyoctanoate) etc. have also been used in CTE. Glycosaminoglycans are the
most abundant polysaccharide present in the body in the form of long unbranched
disaccharide units, where units contain either of two such as N-acetylgalactosamine
or N-acetylglucosamine and a uronic acid such as glucuronate or iduronate.
Hyaluronic acid is a macromolecule made of linear glycosaminoglycans and has been
reported to improve neovascularization of tissues and normalize the left ventricular
function in infracted rat hearts (Ventura et al. 2007). Poly (3-hydroxyoctanoate), Poly
18 Cardiac Tissue Engineering: A Role for Natural Biomaterials
627