Electric Field Assisted Microfluidic Platform for Generation of Tailorable Porous Microbeads as Cell Carriers for Tissue Engineering

Abstract

Injection of cell‐laden scaffolds in the form of mesoscopic particles directly to the site of treatment is one of the most promising approaches to tissue regeneration. Here, a novel and highly efficient method is presented for preparation of porous microbeads of tailorable dimensions (in the range ≈300–1500 mm) and with a uniform and fully interconnected internal porous texture. The method starts with generation of a monodisperse oil‐in‐water emulsion inside a flow‐focusing microfluidic device. This emulsion is later broken‐up, with the use of electric field, into mesoscopic double droplets, that in turn serve as a template for the porous microbeads. By tuning the amplitude and frequency of the electric pulses, the template droplets and the resulting porous bead scaffolds are precisely produced. Furthermore, a model of pulsed electrodripping is proposed that predicts the size of the template droplets as a function of the applied voltage. To prove the potential of the porous microbeads as cell carries, they are tested with human mesenchymal stem cells and hepatic cells, with their viability and degree of microbead colonization being monitored. Finally, the presented porous microbeads are benchmarked against conventional microparticles with nonhomogenous internal texture, revealing their superior performance.

Attractive Pickering Emulsion Gels

“…Therefore, APEGs form at the bottom of the vials with excess oil phase on the top even when the water phase only has a very low volume fraction of 20%, which is unachievable in systems of high internal phase emulsions. [ 28,29 ] The phase diagram of the APEG systems prepared using 20% water is shown in Figure 2e. A minimum concentration of shellac NPs of 0.21 mg mL −1 and a minimum concentration of NH 2 ‐PDMS‐NH 2 polymers of 1.25 mg mL −1 are required for the build‐up of attractive forces between neighboring water droplets to ensure successful gelation.…”

Microcarriers in application for cartilage tissue engineering: Recent progress and challenges

“… Emulsion-solidication Easily scaled-up, simple and convenient, low cost, Limited to low viscosity solutions, suffers from a wide particle size distribution. [ 37 , [49] , [50] , [51] ] Microfluidics Well adapted to produce monodispersed particles with narrow distribution of particle size Low production rate, costly and tedious device preparation [ [56] , [57] , [58] , 62 , 63 , 66 ] Mold methods Easily scaled-up, simple and convenient, low cost Low production rate, costly and tedious device preparation [ 68 , 69 ] Spray-drying Easily scaled-up, low cost Limited polymer range [ 73 , 74 ] Electrostatic spraying Small particle size Very low production rate [ 76 ]

Fig. 2 Schematic diagram of fabrication techniques and application of microcarriers.

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“…Microfluidics, inspired by an extrusion-solidification technique, perfectly overcome the problem of large particle size caused by injection needles. The microfluidics technique is based on the operation, and control of micro-fluids at the micro-scale using micro-pipes [ [56] , [57] , [58] ]. In these techniques, an aqueous polymer solution and typically a nonpolar oil or other fluids are co-extruded to produce consistently-sized droplets [ 59 ].…”

“…In addition to the above-mentioned widely used techniques, many other techniques are available, such as the spray-solidification technique [ 71 , 72 ], electrostatic spraying [ [73] , [74] , [75] ], and the use of electrostatic microdroplets [ 76 ]. Recently, Costantini et al reported a highly efficient method, pulsed electrodripping, to form porous microbeads with tailorable dimensions, and modeled the process to predict the size of the template droplets [ 56 ]. Moreover, Zhang et al designed a simple and low-cost acid-dissolved/alkali-solidified self-sphering shaping for rapid and facile production of chitosan/graphene oxide hybrid MCs via a peristatic pump method ( Fig.…”

Programmable Porous Polymers via Direct Bubble Writing with Surfactant-Free Inks

“… 15 , 18 Additionally, integrating complex 3D geometries 19 − 24 and a range of porosities within a single construct is still challenging. 25 A simple, robust, and scalable technique to produce surfactant-free foams with defined cellular size/structure and 3D cell arrangement with a broad access to aqueous/nonaqueous monomers and minimal shrinkage/postcuring would therefore represent a major step forward. 26 …”