BIONIC HEARTS: Bio-IONomerIC polymers for the regenerative therapy of HEART disease and Stroke

心血管疾病是导致死亡的主要原因，占全球所有死亡人数的32%。心血管疾病也是我们老龄化人口残疾增加的主要原因，缺血性中风是英国严重残疾的最大原因。据估计，英国每年因心血管疾病造成的直接医疗费用为90亿英镑，由于过早死亡和残疾而增加的经济成本为190亿英镑。特别是，中风的可能性受到患者其他心血管疾病病史的显著影响。这种风险的增加可以归因于心肌细胞的丧失，心肌细胞的功能包括调节有节奏的电脉冲和提供心脏的收缩运动。这些功能的受损导致了三个关键问题：心脏机械泵不充分，无法恢复血液和营养供应，以及电传导通路不规律。目前的策略要么支持轻微损伤的心脏组织修复和再生，要么在严重情况下人工取代心脏的电气和机械功能。这些心脏疗法的主要缺点是无法支持心脏修复，同时提供永久性植入物提供的电气和机械支持。因此，一种最佳的治疗设备将通过在能够同时(1)刺激组织生长(2)支持心脏泵送机制中涉及的力、应变和应变率(3)改善流向受损组织的血液和营养物质以及(4)纠正异常电导的电压和电流来解决心血管疾病的这三个关键挑战。仿生心脏的提议旨在利用PI的一项最新创新：能够从生物衍生材料中创建电活性结构，称为“生物离子”聚合物。这些聚合物概括了天然的生物化学环境，同时具有在外加电场下发生大规模变形的能力。该项目旨在为这些生物离子聚合物的制备和合成提供基础数据，在有利于细胞存活的电压下获得高应变，通过电动泵送和带电物种漂移来改善营养流动，最终刺激心肌细胞的生长和成熟。该项目的成果将有助于开发具有现有起搏器和VAD泵送和刺激能力的动态反应再生植入物。通过结合再生潜力和心脏控制，这些设备有可能减少心力衰竭和缺血性中风造成的损害和残疾程度，减少对心脏移植的需求，并提高患者的生活质量。该项目的成果将促进动态反应再生植入物的开发，具有最先进的人工医疗设备(如起搏器和心脏辅助设备)的泵送和刺激能力。通过结合再生潜力和心律控制，所提出的生物离子装置有可能减少心力衰竭和缺血性中风造成的损害和残疾，减少对心脏移植的需求，并提高患者的生活质量。

Cardiovascular diseases (CVDs) are the leading cause of mortality, representing 32% of all deaths globally. CVDs are also the major contributor to rising disability in our aging populations, with ischemic strokes representing the largest cause of severe disability in the UK. The annual economic cost of CVDs to the UK has been estimated at £9 billion for direct healthcare costs, and an additional £19 billion due to premature deaths and disability. In particular, the likelihood of stroke is significantly impacted by a patient history of other CVDs. This increase in risk can be attributed to the loss of cardiomyocyte cells, whose functions include regulating the rhythmic electrical pulses and providing the contractile motion in the heart. The impairment of these functions leads to three key problems: the inadequate mechanical pumping of the heart, inability to restore blood and nutrient supply, and irregular electrical conduction pathways. Current strategies either support the repair and regeneration of heart tissue for minor injuries, or replace the electrical and mechanical function of the heart artificially in severe cases. The primary shortcoming of these cardiac therapies is their inability to support cardiac repair while providing the electrical and mechanical support offered by permanent implants. An optimal therapeutic device would therefore address these three key challenges of CVDs by operating at voltages and currents that can concurrently (1) stimulate tissue growth (2) support the forces, strains and strain rates involved in pumping mechanism of the heart (3) improve blood and nutrient flow to damaged tissues, and (4) correct for aberrant electrical conduction. The BIONIC HEARTS proposal aims to utilise a recent innovation of the PI: the ability to create electroactive constructs derived from biologically derived materials, termed 'bio-ionomeric' polymers. These polymers recapitulate the native biochemical environment, while possessing the ability to undergo large scale deformations in response to an applied electric field. The project aims to provide fundamental data on the fabrication and synthesis of these bio-ionomeric polymers, to obtain high strains at voltages that are conducive to cell viability, to improve nutrient flow through electrically driven pumping and drift of charged species, and finally to stimulate cardiomyocyte growth and maturation. The outcomes of this project will facilitate the development of dynamically responsive regenerative implants with the pumping and stimulation capacity of current pacemakers and VADs. By combining potential for regeneration and cardiac control, these devices have the potential to reduce the extent of damage and disability caused by heart failure and ischaemic strokes, reduce the need for heart transplants, and improve the quality of life of patients. The outcomes of this project will facilitate the development of dynamically responsive regenerative implants with the pumping and stimulation capacity of the state-of-the-art artificial medical devices such as pacemakers and ventricular assist devices. By combining potential for regeneration and cardiac rhythm control, the bio-ionomeric devices proposed have the potential to reduce the extent of damage and disability caused by heart failure and ischaemic strokes, reduce the need for heart transplants, and improve the quality of life of patients.