H2020Индивидуална стипендия2019–2021

HepEDOT · Conductive, self-doping and biodegradable oligoEDOT-heparin biomaterial for improved electromechanical coupling, cardiac cell retention and delivery of paracrine factors

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-04-01 → 2021-03-31
Финансиране от ЕС: 224 934 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Провеждат се тестове с проводими биоматериали, които служат като основа за имплантиране на сърдечни клетки. Това помага за подобряване на електрическата връзка между новите клетки и тъканите на сърцето, за да се увеличи тяхното задържане в организма.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Conductive, self-doping and biodegradable oligoEDOT-heparin biomaterial for improved electromechanical coupling, cardiac cell retention and delivery of paracrine factors

Recent advances in the production of human cardiomyocyte surrogates, particularly those derived from induced-pluripotent stem cells (iPSC-cardiomyocytes), represented a game changer in the field of cell therapy for the treatment of cardiac injury, showing potential reduction in cardiomyocyte apoptosis and infarct size in pre-clinical infarct models. While iPSC-derived cardiomyocyte surrogates do not give rise to ethical concerns and closely resemble the physiology and function of mature cardiomyocytes, their electromechanical activity is still rudimentary. Therefore, the most evident clinical limitations observed in pre-clinical studies using cardiomyocyte surrogates are the absence of cardiac coupling with the host tissue and poor cell retention. Previously, conductive materials have been used to attempt electrical coupling. Although there is no evidence yet for electrical coupling with cardiomyocytes, these have shown to interact electrically with the myocardial tissue. Also, their limited mechanical performance, biocompatibility and electrical stability need to be addressed to make these materials a feasible clinical approach for cardiac repair. The aim of this project was to achieve cardiomyocyte electrical coupling using conductive hydrogels as scaffolds for iPSC-cardiomyocyte implantation. Since the materials would be intended towards clinical use, I aimed to synthesize a biocompatible material and tune the mechanical properties of the hydrogel to match those of the myocardium. An important objective was to study the electrical properties and stability of the resulting material, followed by the development of an electro-stimulation device to pace and study the electrophysiology of cardiomyocytes interfacing the conductive material. By the end of this action, a conductive biomaterial based on PEDOT-derivatives was developed, which can be easily injected and form hydrogels in the heart tissue. The mechanical and electrical properties of the material match those reported in the heart. The conductive hydrogels were biocompatible and were deemed to be a suitable material to facilitate pacing of iPSC-cardiomyocytes, compared to conventional hydrogel scaffolds. This project was performed in close collaboration with the British Heart Foundation at Imperial College London, and the outcomes of this project will advance this technology further into clinically relevant infarct models for the implantation of cardiomyocytes surrogates for the treatment of cardiac infarct.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Cell therapy has emerged as a promising therapeutic strategy for cardiac repair, showing modest cardiomyocyte protection and infarct size reduction. It is under debate whether these outcomes are due to the implanted cells or their paracrine factors, as cells are scarce within a few weeks post-implantation. Regardless, this is still not sufficient to promote cardiac remuscularization and reverse medium to severe myocardium injury and fibrosis. Improved cell retention has been achieved with a substantial bulk of implanted cells, but highly associated to graft-induced arrhythmia, representing a significant challenge for clinical translation. The present study seeks to promote cardiac remuscularization after infarct, by improving the retention of cardiac cells and their paracrine factors without causing graft-induced arrhythmia. To do so, a conductive, self-doping and biodegradable oligoEDOT-heparin biomaterial will be synthesized and studied on in vitro and in vivo cardiac infarct models. The conductive EDOT oligomer moiety is envisaged to act as an electrical sink to shield the cardiac tissue from mismatched electromechanical impulses, while heparin will facilitate cardiac cell support and loading of regenerative factors, besides its recently documented doping capacity. The results of this fellowship are expected to overcome low cell retention and graft-induced arrhythmia, two of the biggest obstacles for translation in cardiac cell therapy, but also contribute with new insights regarding conductivity in materials and biological systems, to multiple fields of materials chemistry, medicine and bioelectronics. The world-class academic environment, collaborations and combined interdisciplinary expertise in biomaterials and cardiovascular sciences make the proposed fellowship activities ideally placed for enhancing my career prospects and consolidating my host and Europe in a leading position for translational research.

Оригинален текст от CORDIS (на английски).

Участници

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonКоординаторОбединеното кралство