REMODELLING OF THE INFARCTED HEART: PIEZOELECTRIC MULTIFUNCTIONAL PATCH ENABLING THE SEQUENTIAL RELEASE OF THERAPEUTIC FACTORS (REBORN)

心脏病仍然是一个主要的社会和医疗负担，每年影响近200万欧洲公民。重生项目汇集了一个由六家科学公司、四家中小企业和两家大型公司合作伙伴组成的财团，他们致力于为心脏病发作(心肌梗死)患者的治疗开发心脏应用医疗设备。心肌梗死会导致心壁纤维化，从而阻碍心脏功能，并意味着心肌梗死后继发心力衰竭的风险很高。目前还没有解决这一主要临床问题的治疗选择。重生项目将使用智能和多功能的生物材料来提供一种新的医疗设备，以心脏贴片的形式应用于心脏，以刺激和支持局部心脏组织重塑。这种压电贴片将与心脏机电耦合，按需提供抗炎、抗纤维化和心肌细胞增殖因子，药物释放由体外的超声波(US)刺激触发。该装置的开发将基于新型智能多功能材料：电纺压电纤维与智能载体相结合，旨在与美国协调工作。为了为开发做好准备，该贴片将在体外和体内进行广泛的表征。加快贴片的开发需要一个有效的体外实验模型，新的3D生物打印技术将被利用来创建组织工程管状心腔形式的3D体外模型，能够利用细胞收缩力量泵送液体。这将提供一种新的体外模型，能够同时进行功能和结构测试。重生项目将开发、验证和准备开发心肌梗死后纤维化的新治疗方案和心脏治疗开发的新工艺，以解决主要的未满足临床症状

Cardiac disease remains a majorsocietal and healthcare burden that affect nearly two million European citizens every year. The REBORN project brings together a consortium of six scientific, four SME, and two large company partners who are committed to making a stepchange to the development of medical devices for cardiac applications for the treatment of people who have suffered from a heart attack (myocardial infarction, MI). A MI causes fibrosis in the heart walls, which impedes cardiac function and means there is a high risk of subsequent heart failure post-MI. There are no current treatment options to address this major clinical problem. The REBORN project will use smart and multifunctional biomaterials to deliver a new medical device in the form of a cardiac patch, to be applied to the heart in order to stimulate and support local heart tissue remodelling. The piezoelectric patch will electromechanically couple with the heart and deliver anti-inflammatory, anti-fibrotic and cardiomyocyte proliferative factors on demand, with drug release triggered by ultrasonic (US) stimulation from outside the body. Development of the device will be based on new smart multifunctional materials: electrospun piezoelectric fibres combined with smart carriers designed to work in harmony with the US. To prepare the ground for exploitation, the patch will be extensively characterised in vitro and in vivo. Accelerating the development of the patch requires an effective in vitro model for experimentation, and novel 3D bioprinting techniques will be exploited to create a 3D in vitro model in the form of a tissue engineered tubular heart chamber, capable of pumping fluid using cell contractile forces. This will give a new in vitro model capable of both functional and structural testing. The REBORN project will develop, validate and prepare for the exploitation new treatment options for post-MI fibrosis and new processes for cardiac therapy development, addressing major unmet cli