Injectable Materials for the Treatment of Myocardial Infarction and Heart Failure: The Promise of Decellularized Matrices

Abstract

Cardiovascular disease continues to be the leading cause of death, suggesting that new therapies are needed to treat the progression of heart failure post-myocardial infarction. As cardiac tissue has a limited ability to regenerate itself, experimental biomaterial therapies have focused on the replacement of necrotic cardiomyocytes and repair of the damaged extracellular matrix. While acellular and cellular cardiac patches are applied surgically to the epicardial surface of the heart, injectable materials offer the prospective advantage of minimally invasive delivery directly into the myocardium to either replace the damaged extracellular matrix or to act as a scaffold for cell delivery. Cardiac-specific decellularized matrices offer the further advantage of being biomimetic of the native biochemical and structural matrix composition, as well as the potential to be autologous therapies. This review will focus on the requirements of an ideal scaffold for catheter-based delivery as well as highlight the promise of decellularized matrices as injectable materials for cardiac repair.

Hydrogels for Cardiac Tissue Repair and Regeneration

“…A solution to these problems was represented by synthetic polymers. Synthetic polymers are capable of being tailored to meet specifi c applications because of their properties like porosity, tensile strength, elastic modulus and degradation rate [65][66][67]. For cardiac tissue engineering applications are used some synthetic polymers including poly (ethylene glycol) (PEG), polylactic acid (PLA), poly (lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), polyurethane (PU), etc [14].…”

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

“…(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.…”

“…(72) Poor cell retention is likely to be a major factor underling the failure of cell-based therapies for MI to achieve consistent and substantial efficacy to date. (34,73) Injected cells in a saline vehicle are lost extremely quickly with the majority lost within the first 24 hours. There has been significant variability in reported rates of retention in preclinical delivery, however, most studies confirm that the vast majority of cells are lost within the first few days post -1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 administration.…”

“…(131)(132)(133) Despite these challenges, there has been some progress in the catheter delivery of biomaterials alone whereby several pre-clinical studies have determined the feasibility using commercially available catheters. (34,79,134,135) The challenge to date remains in combining these two approaches to develop a minimally invasive delivery strategy for advanced biomaterials, which incorporates cells . 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 …”

Heart regeneration after myocardial infarction using synthetic biomaterials

“…PEG has also been combined with natural materials to formulate hydrogels for cell transplantation. Naturally occurring biomaterials allow for the appropriate cell-matrix interactions, thus favoring cell engraftment [56]. The first example is the study by Habib M. et al who PEGylated bovine fibrinogen to synthesize a biocompatible matrix where neonatal rat ventricular CMCs (3x10 6 ) were seeded.…”