Biomaterials for cardiac tissue engineering and regeneration

Abstract

Tissue regeneration after myocardial infarction (MI) represents a major challenge in cardiovascular therapy, as current clinical approaches are limited in their ability to regenerate damaged myocardium. This chapter presents an overview of two emerging strategies based on the use of biomaterials, as stand-alone therapy or in combination with regeneration signals and cells, for regenerating the infarcted heart. One strategy is cardiac tissue engineering, which creates cardiac patches from functional cells seeded in a biomaterial scaffold, bio-inspired to provide the appropriate interface for cellular interactions. Implementation of perfusion bioreactors and pre-vascularization strategies can nowadays produce thicker cardiac patches that are better integrated into the host, thus advancing the realization of this strategy in the clinics. The second strategy, injection of biomaterials, has shown great promise as a stand-alone therapy. The intracoronary delivery of alginate solution that undergoes gelation only at the infarct in the presence of elevated calcium ions, was shown to increase scar thickness and LV dimensions in acute MI models in rats and pigs and was proven safe in phase I/II clinical studies. To enable the spatio-temporal presentation of regeneration factors, the alginate was modified with sulfate groups to mimic the binding of heparin-binding proteins to heparin/heparan-sulfate. When combining alginate-sulfate with the in-situ formed alginate hydrogel, multiple factor delivery was prolonged in ischemic tissues and enabled regeneration and cardiac repair after MI. The chapter emphasizes the increasing important role of biomaterials in various therapeutic strategies aimed at cardiac regeneration.