Bioengineering the Cardiac Conduction System: Advances in Cellular, Gene, and Tissue Engineering for Heart Rhythm Regeneration
Natalia Naumova, Laura Iop
Abstract
Heart rhythm disturbances caused by different etiologies may affect pediatric and adult patients with life-threatening consequences. When pharmacological therapy is ineffective in treating the disturbances, the implantation of electronic devices to control and/or restore normal heart pacing is a unique clinical management option. Although these artificial devices are life-saving, they display many limitations; not least, they do not have any capability to adapt to somatic growth or respond to neuroautonomic physiological changes. A biological pacemaker could offer a new clinical solution for restoring heart rhythms in the conditions of disorder in the cardiac conduction system. Several experimental approaches, such as cell-based, gene-based approaches, and the combination of both, for the generation of biological pacemakers are currently established and widely studied. Pacemaker bioengineering is also emerging as a technology to regenerate nodal tissues. This review analyzes and summarizes the strategies applied so far for the development of biological pacemakers, and discusses current translational challenges toward the first-in-human clinical application.