Catheter-Deliverable Hydrogel Derived From Decellularized Ventricular Extracellular Matrix Increases Endogenous Cardiomyocytes and Preserves Cardiac Function Post-Myocardial Infarction

Abstract

Objectives This study evaluated the use of an injectable hydrogel derived from ventricular extracellular matrix (ECM) for treating myocardial infarction (MI) and its ability to be delivered percutaneously. Background Injectable materials offer promising alternatives to treat MI. While most of the examined materials have shown preserved or improved cardiac function in small animal models, none have been specifically designed for the heart and few have translated to catheter delivery in large animal models. Methods We have developed a myocardial specific hydrogel, derived from decellularized ventricular ECM, which self-assembles when injected in vivo. Female Sprague-Dawley rats underwent ischemia reperfusion followed by injection of the hydrogel or saline 2 weeks later. The implantation response was assessed via histology and immunohistochemistry, and potential for arrhythmogenesis was examined using programmed electrical stimulation 1 week post-injection. Cardiac function was analyzed with magnetic resonance imaging 1 week pre-injection and 4 weeks post-MI. In a porcine model, we delivered the hydrogel using the NOGA guided Myostar catheter, and utilized histology to assess retention of the material. Results We demonstrate that injection of the material in the rat MI model increases endogenous cardiomyocytes in the infarct area and maintains cardiac function without inducing arrhythmias. Furthermore, we demonstrate feasibility of transendocardial catheter injection in a porcine model. Conclusion To our knowledge, this is the first in situ gelling material to be delivered via transendocardial injection in a large animal model, a critical step towards the translation of injectable materials for treating myocardial infarction in humans. Our results warrant further study of this material in a large animal model of myocardial infarction and suggest this may be a promising new therapy for treating myocardial infarction.

Biomaterial‐Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives

“…(41,42) The gel has been shown to retain its gylcosaminoglycan (GAG) content and to allow migration of fibroblasts in vitro. (21) Further studies have demonstrated the ability of the gel to stimulate and allow migration of endothelial and smooth muscle cells in vitro and in vivo in rats. (21,43) It also has a pore size sufficient to promote vasculature infiltration.…”

“…(21) Further studies have demonstrated the ability of the gel to stimulate and allow migration of endothelial and smooth muscle cells in vitro and in vivo in rats. (21,43) It also has a pore size sufficient to promote vasculature infiltration.…”

“…(31,32) Improvement of >100m was demonstrated in treated patients, (improvement of >50 m has been reported as clinically very meaningful, (33) while decreases in walking distance were found in control patients. New York Heart Association (NYHA) index was shown to decrease from a mean of 2.9 in treated patients to 1.96 over six has progressed through pre-clinical studies, (20,21,34) and is currently waiting to start phase I clinical trials (NCT02305602). Use of the native extracellular matrix is advantageous as it provides cells with the complex combination of proteins and polysaccharides seen in vivo.…”

Biological and bactericidal properties of Ag-doped bioactive glass in a natural extracellular matrix hydrogel with potential application in dentistry

“…ECM hydrogels have been successfully isolated and used in several regenerative medicine applications Valentin et al, 2010;Singelyn et al, 2012). ECMs have been shown to promote tissue healing and regeneration in a number of anatomic locations, including skeletal muscle (Marelli et al, 2010;Mase et al, 2010), oesophagus (Nieponice et al, 2009) and urinary bladder (Boruch et al, 2010).…”

Simulated Associating Polymer Networks

“…Injectable hydrogels recently drew media attention as they were shown to be able to repair tissue damaged by a heart attack [15]. Hydrogels that are responsive to specific molecules, such as glucose and antigens, can be used in biosensors [16].…”