Rosebrugh Bldg, Toronto, ON M5S 3G9
Room: RS 211
Abstract: Background: Coronary artery disease is a significant cardiovascular disease that leads to millions of deaths globally. Over time, coronary artery disease can lead to myocardial infarction, cardiomyocyte death, myocardium damage, and ultimately heart failure, due to the limited regenerative potential of cardiomyocytes. Cardiac tissue engineering can be used to repair and replace damaged myocardium to prevent heart failure. Engineered cardiac tissue scaffolds need to be biocompatible, be biodegradable, be functional, and readily accommodate an available cell source. They also have to have mechanical properties and thickness representative of native heart tissue in order to promote angiogenesis and tissue regeneration. However, current cardiac tissue scaffolds have not yet been able to address all these criteria.
Methods: To overcome the limitations with engineered cardiac tissue, a degradable, polar hydrophobic ionic polyurethane (D-PHI PU) can be electrospun to yield a functional cardiac patch that can support the culture of cardiomyocytes. D-PHI PU has a unique immunomodulatory character which addresses several of the biocompatibility limitations of current biomaterials used in this application. D-PHI PU was synthesized, integrated with a degradable linear polycarbonate polyurethane (PCNU), and incorporated into an appropriate solvent to generate a polymer solution. The polymer solution was electrospun with in situ UV cross-linking to generate aligned nanofibre scaffolds. Bulk polymerization was characterized, material surface analysis was carried out by water contact angle studies, and the viability of human embryonic stem cell derived cardiomyocytes was assessed.
Results: 50:50 D-PHI PU:PCNU scaffolds were generated with an average diameter of 410 ± 349 nm and an alignment of 0.60 (perfect alignment = 1, absolute randomness = 0). The crosslinking efficiency of the D-PHI PU/PCNU scaffolds was 93 %, which is comparable to the 96 % obtained for pure D-PHI PU films that were light cured without electrospinning. Contact angle (a proxy for surface energy changes, where a low angle indicates higher surface energy) of the DPHI PU/PCNU scaffolds decreased when compared to pure PCNU scaffolds (44 ± 6° vs. 88 ± 7° respectively) indicating greater adhesion and polarity in the blend. This character could help facilitate enhanced cell attachment. The elastic modulus of D-PHI PU/PCNU wet scaffolds was 55 ± 12 MPa while dry scaffolds had a modulus of 142 ± 59 MPa. The elastic modulus of human myocardium is around 0.5 MPa, and hence further work is required to generate scaffolds with a lower stiffness. Preliminary cardiomyocyte biocompatibility on Geltrex coated D-PHI PU/PCNU scaffolds showed viability that was comparable or better than Geltrex coated tissue culture polystyrene (92 ± 1 % vs 82 ± 1 % respectively after 72 h).
Significance: The developed D-PHI PU/PCNU cardiac patch will be used to overcome biocompatibility, biodegradability, and mechanical property limitations with current engineered cardiac tissue. This cardiac patch could be used for cardiac tissue regeneration and repair after myocardium damage to prevent heart failure.