Modified soft elastomers for cardiac tissue engineering

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 Ca²⁺ 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 Ca²⁺ concentration and Ca²⁺ 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