Alginate Scaffolds for Mesenchymal Stem Cell Cardiac Therapy: Influence of Alginate Composition

Abstract

Despite the success of alginate scaffolds and mesenchymal stem cells (MSCs) therapy in cardiac failure treatment, the impact of the physicochemical environment provided by alginate matrices on cell behavior has never been investigated. The purpose of this work was double: to determine the alginate composition influence on (1) encapsulated rat MSC viability, paracrine activity, and phenotype in vitro and (2) cardiac implantability and in vivo biocompatibility of patch shape scaffolds. Two alginates, differing in composition and thus presenting different mechanical properties when hydrogels, were characterized. In both cases, encapsulated MSC viability was maintained at around 75%, and their secretion characteristics were retained 28 days postencapsulation. In vivo study revealed a high cardiac compatibility of the tested alginates: cardiac parameters were maintained, and rats did not present any sign of infection. Moreover, explanted hydrogels appeared surrounded by a vascularized tissue. However, scaffold implantability was highly dependent on alginate composition. G-type alginate patches, presenting higher elastic and Young moduli than M-type alginate patches, showed a better implantation easiness and were the only ones that maintained their shape and morphology in vivo. As a consequence of alginate chemical composition and resulting hydrogel structuration, G-type alginate hydrogels appear to be more adapted for cardiac implantation.

3D Cell Culture in Alginate Hydrogels

“…Immobilizing myocardial stem cells within a scaffold ensures that they will remain within the cardiac tissue after implantation. Ceccaldi et al [138] has studied the influence of alginate composition on mesenchymal stem cells in alginate scaffolds. Their conclusion was the G-rich alginate hydrogels provided the most appropriate milieu for MSCs intended for cardiac therapy.…”

Preconditioning Stem Cells for In Vivo Delivery

“…104 The MSCs encapsulated in alginate also retained high viability and trophic functions (e.g., secretion of VEGF, IGF-1, FGF-2, and HGF), while minimizing the immune response once injected into hearts. 105 The injection of encapsulated MSCs in hydrogel functionalized with PGE2 in an MI model of rat heart reduced scar area and improved left ventricular functions. 106 Encapsulated MSCs in gelatin/laminin gels enhanced survival while reducing the neuro-inflammation in ischemic rat hippocampus.…”

Mechanostimulation Protocols for Cardiac Tissue Engineering

“…In this case, a scaffold should provide a structured environment with tissue-specific mechanical properties and the ability to integrate with surrounding tissue [22, 23]. Biomaterials used for scaffold fabrication include biological molecules (e.g., alginate, collagen, fibrin, and hyaluronan) and biomimetic synthetic polymers (e.g., polylactic and polyglycolic acids and their copolymers, polycaprolactone) where a specific supramolecular architecture is designed to sustain the differentiation and functional organization of the seeded cells [24–31]. …”