Conduction system disorders, defective electrogenesis in the heart, lead to slow heart rates that are insufficient to support the circulation, necessitating the implantation of electronic pacemakers. Although effective, current electronic devices have lead or generator malfunction, lack of autonomic responsiveness, undesirable interactions with strong magnetic fields, and device-related infections. Biological pacemakers, generated by somatic gene transfer, cell fusion, or cell transplantation, provide an alternative to electronic devices.
Here we show that the exposure of rat quiescent ventricular cardiomyocytes to a silk-fibroin hydrogel activates the direct conversion of the quiescent cardiomyocytes to pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin. The silk-fibroin-induced pacemaker cells exhibited functional and morphological features of genuine sinoatrial-node cardiomyocytes in vitro, and pacemaker cells generated via the injection of silk fibroin in the left ventricles of rats functioned as a surrogate in situ sinoatrial node. Biomaterials with suitable surface structure, mechanics, and biochemistry could facilitate the scalable production of biological pacemakers for human use.
The study entitled “Biomaterial-induced conversion of quiescent cardiomyocytes into pacemaker cells in rats” was published online in Nat Biomed Eng. 2021 Nov 22.(doi: 10.1038/s41551-021-00812-y.). Dr. Yu-Feng Hu leads the research team. The work is a collaborative effort with Dr. Tze-Wen Chung , Terry B. J. Kuo, and Shien-Fong Lin (National Yang Ming Chiao Tung University), Dr. An-Sheng Lee (Mackay Medical College), Dr. Ruey-Bing Yang and Chien-Chang Chen (IBMS), and Dr. Shih-Ann Chen (Taichung Veterans General Hospital) and Shih-Lin Chang (Taipei Veterans General Hospital).