Modified soft elastomers for cardiac tissue engineering
Chenghao Zhu
10.4225/03/58d9c2ccec94f
https://bridges.monash.edu/articles/thesis/Modified_soft_elastomers_for_cardiac_tissue_engineering/4792651
Poly (glycerol
sebacate) (PGS) is a biodegradable crosslinked polyester elastomer. Due to its
hemocompatibility, biodegradability, soft and flexible mechanical properties,
PGS has been studied to replace or repair soft tissues in mechanically dynamic
environments such as myocardial tissue. In this project, PGS based scaffolds
were designed and fabricated to address some of the drawbacks of PGS and enhance
the performance of cardiomyocytes which is the main component of myocardial
tissue. <br>
<br>
The properties of PGS were modified by blending and/or
copolymerizing PGS with another biocompatible polymer,
poly(3-hydroxybutyrate-4-hydroxybute) (P34HB). These blends provided a wider
range of mechanical properties without losing the elastomeric characteristics
of PGS. The degradation rates of the blends were also reduced in comparison
with PGS. Since a patient’s recovery from myocardial infarction (MI) is a long
process, slower degradation rates can provide more enduring mechanical support
for myocardial tissue. <br>
<br>
In the second part of this thesis, micropatterns exhibiting
repetitive grooves and crests were fabricated on the surface of PGS substrates.
More aligned cardiomyocytes, better beating behavior and higher amplitude of
Ca<sup>2+</sup> transients could be achieved using substrates with such topographical
features. Cardiomyocytes were confined by the grooves, and formed anisotropic
structures reminiscent of natural myocardial tissue. <br>
<br>
Brain derived neurotrophic factor (BDNF) small molecule
mimetic was copolymerized into the PGS network and slowly released from the
polymer during its bio-degradation. Recent studies showed that BDNF is an
important factor for cardiomyocytes normal contraction and relaxation, not only
in conditions such as hypoxia and ischemia, but during normal physiological
function. The contractile force of myocardium is controlled by intracellular
Ca<sup>2+</sup> concentration and Ca<sup>2+</sup> transients regulation regulates beating and
provides a constant cardiac output. The amplitude of calcium transients of
cardiomyocytes was elevated in the presence of BDNF mimetic, similar to BDNF
full protein. Thus BDNF mimetic copolymerized in the PGS network could provide
a potential therapy for insufficient cardiac output.
2017-03-28 01:56:26
Poly (glycerol sebacate)
Bioelastomer
Cardiomyocytes
Micropatterning
Cardiac tissue engineering
Materials Engineering not elsewhere classified