IGF-1 loaded injectable microspheres for potential repair of the infarcted myocardium

Abstract

The use of injectable scaffolds to repair the infarcted heart is receiving great interest. Thermosensitive polymers, in situ polymerization, in situ cross-linking, and self-assembling peptides are the most investigated approaches to obtain injectability. Aim of the present work was the preparation and characterization of a novel bioactive scaffold, in form of injectable microspheres, for cardiac repair. Gellan/gelatin microspheres were prepared by a water-in-oil emulsion and loaded by adsorption with Insulin-like growth factor 1 to promote tissue regeneration. Obtained microspheres underwent morphological, physicochemical and biological characterization, including cell culture tests in static and dynamic conditions and in vivo tests. Morphological analysis of the microspheres showed a spherical shape, a microporous surface and an average diameter of 66 ± 17µm (under dry conditions) and 123 ± 24 µm (under wet conditions). Chemical Imaging analysis pointed out a homogeneous distribution of gellan, gelatin and Insulin-like growth factor-1 within the microsphere matrix. In vitro cell culture tests showed that the microspheres promoted rat cardiac progenitor cells adhesion, and cluster formation. After dynamic suspension culture within an impeller-free bioreactor, cells still adhered to microspheres, spreading their cytoplasm over microsphere surface. Intramyocardial administration of microspheres in a cryoinjury rat model attenuated chamber dilatation, myocardial damage and fibrosis and improved cell homing. Overall, the findings of this study confirm that the produced microspheres display morphological, physicochemical, functional and biological properties potentially adequate for future applications as injectable scaffold for cardiac tissue engineering.

Conductive and Semiconductive Nanocomposite‐Based Hydrogels for Cardiac Tissue Engineering

“…For example, Rosellini et al used gelatin/gellan microparticles as injectable scaffolds to regenerate the myocardium. [30] In general, many advances have been made in the field of tissue engineering and its evolution continues. Some technologies and trends that have a positive impact on this field include the use of new sources of stem cells, 3D bioprinting, the use of patches, injectable hydrogels, and microparticles.…”

Polymeric Biomaterials for the Treatment of Cardiac Post-Infarction Injuries

“…Moreover, by in vitro cell culture assays, the influence of particle diameter on cardiac progenitor cells was demonstrated, indicating a preferential cell adherence to microparticles with a smaller size [ 76 ]. After loading with insulin-like growth factor-1 (IGF-1) by absorption, in vivo experiments were performed, finding an attenuated chamber dilatation and myocardial damage and fibrosis, together with an improved cell homing [ 77 ].…”

De novo Drug Delivery Modalities for Treating Damaged Hearts: Current Challenges and Emerging Solutions

“…The results demonstrated cardiac progenitor cell adhesion to the MP's surface. These microspheres also reduced myocardial damage and improved overall cardiac function and successful cell engraftment ( 87 ).…”