3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization

Abstract

In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). In this work, a method to fabricate 3D scaffolds by the assembly of bicomponent microgels made of sodium alginate and gelatin was proposed. As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions.

Designing Advanced Drug Delivery Systems: Core-Shell Alginate Particles through Electro-Fluid Dynamic Atomization

“…EFDA is a non-continuous dropping mode, strongly influenced by the local polymer density and molecular weight and, consequently, by the electrical forces required to overcome the surface tension of the drop at the tip of the needle [ 24 ]. The formed droplets are collected into a crosslinking bath (i.e., CaCl 2 ) to allow their ionic gelation to finally obtain spherical beads of homogeneous size prior to reaching the excess of charge on the droplet surface [ 25 ]. The processing of ionotropic polymers as alginates allows for the entrapment of cells, active molecules, and/or pharmaceutical species to form chemically functionalized carriers suitable for differently addressing the biological response [ 25 , 26 ].…”

“…The formed droplets are collected into a crosslinking bath (i.e., CaCl 2 ) to allow their ionic gelation to finally obtain spherical beads of homogeneous size prior to reaching the excess of charge on the droplet surface [ 25 ]. The processing of ionotropic polymers as alginates allows for the entrapment of cells, active molecules, and/or pharmaceutical species to form chemically functionalized carriers suitable for differently addressing the biological response [ 25 , 26 ]. Morphology and particle sizes can be highly adjusted by accurately setting process parameters (i.e., polymer concentration, voltage applied, needle diameter, working distance) [ 27 , 28 ].…”

Designing Advanced Drug Delivery Systems: Core-Shell Alginate Particles through Electro-Fluid Dynamic Atomization

“…EFDA is a non-continuous dropping mode, strongly influenced by the local polymer density and molecular weight, and, consequently, by the electrical forces required to overcome the surface tension of the drop at the tip of needle [25]. The formed droplets are collected into a crosslinking bath (i.e., CaCl2), to allow their ionic gelation to finally obtain spherical beads with homogeneous size prior to reach the excess of charge on the droplet surface [26,27]. The processing of ionotropic polymers as alginates allows for the entrapment of cells, active molecules and/or pharmaceutical species to form chemically functionalized carriers suitable to differently address the biological response [27,28].…”

“…The formed droplets are collected into a crosslinking bath (i.e., CaCl2), to allow their ionic gelation to finally obtain spherical beads with homogeneous size prior to reach the excess of charge on the droplet surface [26,27]. The processing of ionotropic polymers as alginates allows for the entrapment of cells, active molecules and/or pharmaceutical species to form chemically functionalized carriers suitable to differently address the biological response [27,28]. Morphology and particle sizes can be highly adjusted by accurately setting process parameters (i.e., polymer concentration, voltage applied, needle diameter, working distance) [29,30].…”

Polydopamine-Coated Alginate Microgels: Process Optimization and In Vitro Validation

“…However, as reported in previous works, sodium alginates can present some limits for in vitro applications, mainly due to low adhesive properties—not comparable with those of other natural biopolymers such as gelatin or chitosan [ 12 , 13 ]—and the tendency to rapidly degrade, just after few weeks in cell culture, thus compromising their chemical and mechanical properties [ 14 ].…”