Heart rate control with bioengineered pacemakers

使用生物工程起搏器控制心率

• 批准号: 10638779
• 负责人: Hee Cheol Cho
• 金额: $ 43.81万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-05 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10638779
• 关键词: Acute; Animal Model; Atrioventricular Block; Biological; Biological Pacemakers; Biomedical Engineering; Bradyarrhythmias; Cardiac Myocytes; Cardiomyopathies; Chronic; Clinical; Congenital Heart Block; Congenital Heart Defects; Data; Development; Devices; Disease; Dose; Embryo; Excision; Family suidae; Fibrosis; Foreign Bodies; Gene Delivery; Gene Transfer; Genetic; Goals; Heart Block; Heart Rate; Heart failure; Implant; In Situ; Infection; Longevity; Longitudinal Studies; Mediating; Messenger RNA; Modality; Modeling; Molecular; Myocardium; Natural regeneration; Operative Surgical Procedures; Pacemakers; Patients; Procedures; Rattus; Research; Rodent Model; Route; Signal Transduction; Sinoatrial Node; Site; Symptoms; Technology; Testing; Time; Tissue Engineering; Tissue constructs; Tissues; Transcend; Transforming Growth Factor beta; Transgenes; Ventricular; Work; aortic valve replacement; base; cardiac pacing; clinical outcome measures; clinical practice; clinically relevant; comorbidity; congenital heart disorder; efficacy evaluation; electronic pacemaker; gene therapy; heart rhythm; implantable device; miniaturize; minimally invasive; new technology; nodal myocyte; patient subsets; pediatric patients; porcine model; regenerative tissue; trait; transcription factor; transgene expression

Project Summary/Abstract For patients with symptomatic bradyarrhythmias, the current and only treatment is to implant an electronic pacemaker. Nearly all of the current research regarding rhythm management, including the leadless pacemakers, are invested in incremental progress in miniaturizing the indwelling devices. While the devices can provide stable and long-term pacing, the technology is far from ideal with problems inherent to the pacing technology and to foreign body issues due to the indwelling hardware. The problems can be severe for pediatric patients with congenital heart block as multiple and invasive surgeries are needed for replacement or revision of the implanted devices over the patients’ lifetime. Device-related acute problems are rising as well, include infections with the generator and/or leads wire, which require surgical removal of the entire implanted device. Bioengineered pacemakers, in contrast, transcend all current modalities by creating hardware-free cardiac pacing. We have previously demonstrated that minimally-invasive delivery of a natural transcription factor gene could pace the ventricles in both small and large animal models of complete heart block. The enabling technology is based on regenerative tissue engineering in which ordinary heart muscle is converted to specialized pacemaker tissue construct in situ with a focally delivered genetic construct. To advance this concept to clinical practice, two questions need to be answered: 1) how long can the bioengineered pacemaker retain its function, and 2) how well the bioengineered pacemaker be able to function in diseased myocardium since most patients with a pacemaker are also presented with underlying diseases in the myocardium. In this proposal, we will directly answer these questions by employing chronic heart block models that are known to elicit traits of heart failure, and examining the efficacy and durability of the gene therapy in a longitudinal study.

项目总结/文摘