Towards an elastin-based hydrogel platform for the repair of myocardial infarction

Abstract

Event Abstract Back to Event Towards an elastin-based hydrogel platform for the repair of myocardial infarction Paolo Contessotto1, Gesmi Milcovich1*, Renza Spelat1*, Grazia Marsico1*, Ankit Chaturvedi2*, Doriana Orbanić3*, Tatjana Flora3*, Mark Da Costa1, 4, Mindaugas Rackauskas5*, Heinz Amenitsch6*, Mike Mccartin2*, José Carlos Rodriguez-Cabello3*, Lokesh Joshi7*, Peter Dockery8*, Michelle Kilcoyne7, 9* and Abhay Pandit1 1 National University of Ireland, CURÁM, Centre for Research in Medical Devices, Ireland 2 Vivasure Medical Limited, Ireland 3 Universidad de Valladolid, Ciber-BBN, G.I.R. Bioforge, Spain 4 University College Hospital Galway, Ireland 5 Mater Misericordiae University Hospital, Ireland 6 Institut of Inorganic Chemistry, Graz University of Technology, Austria 7 National University of Ireland, Glycoscience Group, Ireland 8 National University of Ireland, Anatomy, School of Medicine, Ireland 9 National University of Ireland, Microbiology, School of Natural Sciences, Ireland Introduction Elastin is one of the main components of the extracellular matrix (ECM) and has been investigated as a potential therapeutic biomaterial in the treatment of several diseases, such as myocardial infarction [1]. The intrinsic physical elastic properties of elastin-like recombinamers and their interaction with relevant glycosylation in the ECM can be exploited by developing a tailored biomaterial. The objectives of this study are to fabricate an injectable elastin-based hydrogel based on the glycoprofile in normal and ischemic cardiac muscle. We hypothesize that a naturally-inspired glyco-functionalised injectable elastin-like hydrogel will preserve cardiac functionality by the enhancement of cardiomyocyte proliferation. Materials and methods Hydrogel fabrication: Elastin-like recombinamers (ELRs) were functionalised with azide and cyclooctyne groups for crosslinking. The hydrogel construct was characterized by rheology, NMR, and Synchrotron Radiation SAXS (SRSAXS). Moreover, further degradation studies were conducted using elastase (Sigma). The hydrogel was stained with 1% Alcian Blue solution before epicardial injection in the myocardium of a healthy lamb heart. Glycoprofile analysis: Lectin histochemistry and lectin microarray analyses were performed on left ventricle cryosections from healthy male Lewis and Dark Agouti rats (n=5). Myocardial infarction in vivo models: Induction of myocardial infarction is being performed on Romanov sheep (n=7) to better mimic human conditions [2], while cryoinjury method is adopted as a method to reproduce the ischemic event in Danio rerio [3]. All animals were sacrificed after approval by the respective Institutional Ethics Committee. Statistical analysis was performed using Minitab Software. Results and Discussion ELRs-based hydrogel was fabricated and optimized; the optimal gelling time before injection was found between 10 and 12 minutes at room temperature and its successful integration across the cardiomyocytes confirmed by hematoxylin and eosin (H&E) and Wheat Germ Agglutinin (WGA) lectin staining, confirming its potential application for in vivo studies [4]. Glycoprofile analysis was carried out in healthy myocardial left ventricle rat tissue, using a panel of lectins which bind to specific glycan residues that are involved in cardiac signalling and functionality, such as sialic acids (Neu) and N-acetylglucosamine (GlcNAc) [5]. Distinct patterns of binding due to the differential glycosylation in capillaries and cardiomyocytes membranes were found by lectin histochemistry analysis and their presence further validated by lectin microarray technology. Conclusion An ELRs-based hydrogel was optimised for injection through the myocardial walls. The assessment of the glyco-profiles in healthy myocardial tissue was completed to have a baseline before further analysis in the ischemic samples. Glycoprofile comparative analysis between a non-regenerative and a self-regenerative model in Danio rerio can further enable us to tailor our system towards a regenerative system. Seventh Framework Programme Grant Agreement no.: 317304; Centre for Microscopy & Imaging at the National University of Ireland Galway funded by Irish Government’s Programme for Research in Third Level Institutions, Cycles 4 and 5, National Development Plan 2007-2013