An injectable alginate/extra cellular matrix (ECM) hydrogel towards acellular treatment of heart failure

Abstract

As treatments for myocardial infarction (MI) continue to improve, the population of people suffering from heart failure (HF) is rising significantly. Novel treatment strategies aimed at achieving long-term functional stabilization and improvement in heart function post MI include the delivery of biomaterial hydrogels and myocardial matrix-based therapies to the left ventricle wall. Individually alginate hydrogels and myocardial matrix-based therapies are at the most advanced stages of commercial/clinical development for this potential treatment option. However, despite these individual successes, the potential synergistic effect gained by combining the two therapies remains unexplored. This study serves as a translational step in evaluating the minimally invasive delivery of dual acting alginate-based hydrogels to the heart. We have successfully developed new production methods for hybrid alginate/extracellular matrix (ECM) hydrogels. We have identified that the high G block alginate/ECM hybrid hydrogel has appropriate rheological and mechanical properties (1.6 KPa storage modulus, 29 KPa compressive modulus and 14 KPa dynamic modulus at day 1) and can be delivered using a minimally invasive delivery device. Furthermore, we have determined that these novel hydrogels are not cytotoxic and are capable of enhancing the metabolic activity of dermal fibroblasts in vitro (p < 0.01). Overall these results suggest that an effective minimally invasive HF treatment option could be achieved by combining alginate and ECM particles.

A Natural Xenogeneic Endometrial Extracellular Matrix Hydrogel Toward Improving Current Human in vitro Models and Future in vivo Applications

“…The rapid remodeling of the ECM hydrogels could present some issues when considering in vitro application, reducing the time of exposition of their natural bioactive properties to their environment. In this context, the use of chemical crosslinking (i.e., Genipin; Výborný et al, 2019) or a semi-synthetic mixture with more stable compounds (Valdez et al, 2017;Curley et al, 2019) should be investigated as an alternative. In contrast to previous studies, ICE6-ICE7 and EEC-ESC constructs presented vimentin positive cells with few E-cadherin positive cells on the surface with no apical polarization, likely due to a lack of hormonal stimulation (Wang et al, 2012).…”

Injectable Myocardial Matrix Hydrogel Mitigates Negative Left Ventricular Remodeling in a Chronic Myocardial Infarction Model

“…Currently, there are various injectable biomaterials being investigated for the treatment of myocardial infarction (MI). Although there have been some studies that evaluate these therapeutics in a chronic MI model where the scar has fully formed, the majority of studies have focused on acute or subacute MI models, whereby the material is injected immediately or a short time frame following MI before full scar formation, respectively ( 2 , 3 , 4 , 5 ). We previously developed a decellularized injectable extracellular matrix (ECM) hydrogel derived from porcine left ventricular (LV) myocardial tissue as a tissue engineering approach for treatment after MI ( 6 ).…”

Rational Design of a Triple-Layered Coaxial Extruder System: in silico and in vitro Evaluations Directed Toward Optimizing Cell Viability

“…These values were 26, 34, and 40 kPa and the three of them fell within the material’s printing window, as they allowed controlled and continuous deposition of a filament. An alginate-based bioink embedded with MG-63 cells was chosen for this evaluation since alginate is a widely used biocompatible material, easily extrudable and features rapid crosslinking upon exposition to divalent cations, which enables excellent shape fidelity in bioprinted constructs[ 29 ].…”