18.3.3 Fibrin
Fibrin is a naturally occurring blood clotting protein and is FDA approved for use as
a surgical sealant. The fibrin network has a nanometric fibrous structure, which upon
treatment with thrombin can create fibrin gel. Upon introduction into the heart, the
fibrin gels can get replaced by natural ECM and therefore, it serve as a temporary
scaffold in CTE (Grassl et al. 2003). Fibrin glue (Christman et al. 2004), and
hydrogel scaffolds (Kaiser et al. 2019) have been explored as possible cardiac grafts.
Thomson et al. described a high-density microtemplated fibrin scaffold seeded with a
tri-cell mixture of CM, Epithelial cells (ECs), and fibroblasts to mimic native cardiac
tissue in structure and cellular composition (Thomson et al. 2013).
18.3.4 Alginate
Alginate of algal origin has also been used as natural biomaterials for CTE. Sodium
alginate has been extensively used as hydrogel for encapsulation of cells and
delivery of growth factors for CTE (Sun et al. 2010). The physico-chemical
properties such as gelation time, uniformity, mechanical strength, tensile properties,
and mechanics of alginate gel formation can be controlled or altered by using
different cation sources such as CaCl 2 , CaSO 4 , and CaCO 3 (Kuo and Ma 2001),
temperature (Drury et al. 2004) and molecular weight distribution (Augst et al.
2006). Alginates containing higher amount of glucuronic acid (G-type) formed
stiffer gels due to the presence of diaxial links and had higher elastic and Young's
moduli than mannuronic acid (M-type) alginate gels and were more adaptable for
cardiac implantation (Ceccaldi et al. 2012). Fetal CMs, seeded onto alginate
hydrogels, stimulated neovascularization and healing of the infracted myocardium
in a rat model of MI (Leor et al. 2000). In addition to hydrogel system, alginate has
also been used to develop fibrous scaffold by electrospinning and porous scaffold
by freeze-drying (Lee et al. 2009). Macroporous scaffolds with interconnected pores
showed efficient cell seeding and maintained high metabolic activity of the cardiac
cells (Dar et al. 2002).
In earlier studies, it was difficult to electrospun the alginates as continuous and
uniform nanofibers due to lack of chain entanglements caused by rigid and
extended chain conformation. Electrospinning of alginates could successfully be
done by using glycerol as a co-solvent with water in different volume ratio (Nie
et al. 2008) and combining with water–soluble synthetic polymers such as polyethylene oxide (PEO) and poly (vinyl alcohol) (PVA). Alginate/PEO nanofibers
showed good uniformity, integrity, cell adherence, cell viability and cellular
compatibility (Narayan and Miqin 2007). The cell adherence of alginate scaffolds
could be increased by incorporation of natural peptides such as fibronectin, laminin,
nephronectin or immobilization of RGD (arginine-glycine-aspartic acid) peptides
(Shachar et al. 2011).
624
P. Pushp and M. K. Gupta
Fibrin is a naturally occurring blood clotting protein and is FDA approved for use as
a surgical sealant. The fibrin network has a nanometric fibrous structure, which upon
treatment with thrombin can create fibrin gel. Upon introduction into the heart, the
fibrin gels can get replaced by natural ECM and therefore, it serve as a temporary
scaffold in CTE (Grassl et al. 2003). Fibrin glue (Christman et al. 2004), and
hydrogel scaffolds (Kaiser et al. 2019) have been explored as possible cardiac grafts.
Thomson et al. described a high-density microtemplated fibrin scaffold seeded with a
tri-cell mixture of CM, Epithelial cells (ECs), and fibroblasts to mimic native cardiac
tissue in structure and cellular composition (Thomson et al. 2013).
18.3.4 Alginate
Alginate of algal origin has also been used as natural biomaterials for CTE. Sodium
alginate has been extensively used as hydrogel for encapsulation of cells and
delivery of growth factors for CTE (Sun et al. 2010). The physico-chemical
properties such as gelation time, uniformity, mechanical strength, tensile properties,
and mechanics of alginate gel formation can be controlled or altered by using
different cation sources such as CaCl 2 , CaSO 4 , and CaCO 3 (Kuo and Ma 2001),
temperature (Drury et al. 2004) and molecular weight distribution (Augst et al.
2006). Alginates containing higher amount of glucuronic acid (G-type) formed
stiffer gels due to the presence of diaxial links and had higher elastic and Young's
moduli than mannuronic acid (M-type) alginate gels and were more adaptable for
cardiac implantation (Ceccaldi et al. 2012). Fetal CMs, seeded onto alginate
hydrogels, stimulated neovascularization and healing of the infracted myocardium
in a rat model of MI (Leor et al. 2000). In addition to hydrogel system, alginate has
also been used to develop fibrous scaffold by electrospinning and porous scaffold
by freeze-drying (Lee et al. 2009). Macroporous scaffolds with interconnected pores
showed efficient cell seeding and maintained high metabolic activity of the cardiac
cells (Dar et al. 2002).
In earlier studies, it was difficult to electrospun the alginates as continuous and
uniform nanofibers due to lack of chain entanglements caused by rigid and
extended chain conformation. Electrospinning of alginates could successfully be
done by using glycerol as a co-solvent with water in different volume ratio (Nie
et al. 2008) and combining with water–soluble synthetic polymers such as polyethylene oxide (PEO) and poly (vinyl alcohol) (PVA). Alginate/PEO nanofibers
showed good uniformity, integrity, cell adherence, cell viability and cellular
compatibility (Narayan and Miqin 2007). The cell adherence of alginate scaffolds
could be increased by incorporation of natural peptides such as fibronectin, laminin,
nephronectin or immobilization of RGD (arginine-glycine-aspartic acid) peptides
(Shachar et al. 2011).
624
P. Pushp and M. K. Gupta