Biological pacemaker: from biological experiments to computational simulation.

Pacemaking dysfunction has become a significant disease that may contribute to heart rhythm disorders, syncope, and even death. Up to now, the best way to treat it is to implant electronic pacemakers. However, these have many disadvantages such as limited battery life, infection, and fixed pacing rate. There is an urgent need for a biological pacemaker (bio-pacemaker). This is expected to replace electronic devices because of its low risk of complications and the ability to respond to emotion. Here we survey the contemporary development of the bio-pacemaker by both experimental and computational approaches. The former mainly includes gene therapy and cell therapy, whilst the latter involves the use of multi-scale computer models of the heart, ranging from the single cell to the tissue slice. Up to now, a bio-pacemaker has been successfully applied in big mammals, but it still has a long way from clinical uses for the treatment of human heart diseases. It is hoped that the use of the computational model of a bio-pacemaker may accelerate this process. Finally, we propose potential research directions for generating a bio-pacemaker based on cardiac computational modeling.