Influence of injectable microparticle size on cardiac progenitor cell response

Abstract

Introduction: Injectable scaffolds are emerging as a promising strategy in the field of myocardial tissue engineering. Among injectable scaffolds, microparticles have been poorly investigated. The goal of this study was the development of novel gelatin/gellan microparticles that could be used as an injectable scaffold to repair the infarcted myocardium. In particular, the effect of particle size on cardiac progenitor cell response was investigated. Methods: Particles were produced by a water-in-oil emulsion method. Phosphatidylcholine was used as a surfactant. Particles with different diameter ranges (125-300 µm and 350-450 µm) were fabricated using two different surfactant concentrations. Morphological, physicochemical, and functional characterizations were carried out. Cardiac progenitor cell adhesion and growth on microparticles were tested both in static and dynamic suspension culture conditions. Results: Morphological analysis of the produced particles showed a spherical shape and porous surface. The hydrophilicity of particle matrix and the presence of intermolecular interactions between gellan and gelatin were pointed out by the physicochemical characterization. A weight loss of 75 ± 5 % after 90 days of hydrolytic degradation was observed. Injectability through a narrow needle (26 G) and persistence of the microparticles at the injection site were preliminarily verified by ex vivo test. In vitro cell culture tests showed a preservation of rat cardiac progenitor biologic properties and indicated a preferential cell adherence to microparticles with a smaller size. Conclusion: Overall, the obtained results indicate that the produced gelatin/gellan microparticles could be potentially employed as injectable scaffolds for myocardial regeneration.

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

“…Phosphatidylcholine (PC), a phospholipid from biological membranes, was used as surfactant. As already demonstrated, 19 Gel/GE microspheres present a marked capability to absorb water, which makes them very similar to soft tissues as the myocardium. Moreover, the hydrogelic nature of the proposed microspheres can favor the controlled release of bioactive agents.…”

“…Gel/GE microspheres were prepared by a water-in-oil emulsion, using a procedure adapted from our previous work. 19 Here the preparation procedure was optimized to obtain particles with spherical shape and reduced diameters. The water phase was made by 50 ml of a 2% (w/v) solution of the two biopolymers (Gel/GE, weight ratio 30/70) in bi-distilled water; the oil phase was 400 ml of a 1.5% (w/v) solution of PC in dichloromethane.…”

“…Based on microspheres swelling behavior knowledge, 19 a volume of IGF-1 solution adequate to achieve full adsorption was used in both methods (A and B).…”

“…18,19 In a previous study, we reported the preparation of gelatin/gellan (Gel/GE) microparticles and we demonstrated that their physicochemical and functional properties are adequate for tissue engineering application. 19 Moreover, we investigated the effect of their diameter on cardiac progenitor cells (CPCs), showing a preferential CPCs adhesion to microparticles with a smaller size. 19 However, even the smaller particles of our previous study had a swollen diameter above 200 µm.…”

“…19 Moreover, we investigated the effect of their diameter on cardiac progenitor cells (CPCs), showing a preferential CPCs adhesion to microparticles with a smaller size. 19 However, even the smaller particles of our previous study had a swollen diameter above 200 µm. As demonstrated in literarature, injectable microspheres for tissue engineering should have a diameter below 200 µm, to allow adequate diffusion of oxygen, nutrients and metabolic products.…”