Injectable Acellular Hydrogels for Cardiac Repair

Abstract

Injectable hydrogels are being developed as potential translatable materials to influence the cascade of events that occur after myocardial infarction. These hydrogels, consisting of both synthetic and natural materials, form through numerous chemical crosslinking and assembly mechanisms and can be used as bulking agents or for the delivery of biological molecules. Specifically, a range of materials are being applied that alter the resulting mechanical and biological signals after infarction and have shown success in reducing stresses in the myocardium and limiting the resulting adverse left ventricular (LV) remodeling. Additionally, the delivery of molecules from injectable hydrogels can influence cellular processes such as apoptosis and angiogenesis in cardiac tissue or can be used to recruit stem cells for repair. There is still considerable work to be performed to elucidate the mechanisms of these injectable hydrogels and to optimize their various properties (e.g., mechanics and degradation profiles). Furthermore, although the experimental findings completed to date in small animals are promising, future work needs to focus on the use of large animal models in clinically relevant scenarios. Interest in this therapeutic approach is high due to the potential for developing percutaneous therapies to limit LV remodeling and to prevent the onset of congestive heart failure that occurs with loss of global LV function. This review focuses on recent efforts to develop these injectable and acellular hydrogels to aid in cardiac repair.

Influence of matrix and bulk behaviour of an injectable hydrogel on the survival of encapsulated cardiac cells

“…The injectable hydrogels are well known for high tissue-like water content, limited surgical invasion and bulking effects. 6 The proper porosity (to promote immunoisolation and metabolite diffusion), 7 and degradation proportional to allow the cell growth and moldability to ll the defective regions are some of the essential requirements for tissue engineering. 8 The hydrogels can be prepared from both natural and synthetic polymers by physical (polyelectrolyte complexation, hydrogen bonding and hydrophobic association) or chemical (free radical polymerization, irradiation crosslinking) methods.…”

Hydrogels for Cardiac Tissue Repair and Regeneration

“…In another study, collagen injections were administered at 1-week-old rat infarcts and it was observed that infarct thickness, stroke volume and ejection fraction have increased compared to the control (saline injection) [6]. Suuronen E.J.…”

“…Molecules (with repair and/or regeneration capacities of the damaged tissue) are encapsulated in the hydrogel and released locally over time (the hydrazone bond is then broken and occurs the molecules release from nanoparticles). In several studies it was reported that polymer matrices can be used to sustain the release of encapsulated molecules for up to 100 days and the release profi le initially showed a quick release followed by a slower release rate [6][7][8][9][10]. …”

Materials for cardiac tissue engineering

“…Interestingly, injectable hydrogels also preserve cardiac function when administrated without cells, demonstrating that the cells may not be responsible [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. For instance, promising preliminary results obtained in rodents and pigs using alginate [45,46] led to the first clinical trials in MI patients (NCT00557531 and NCT01226563) [55].…”