Combining submerged electrospray and UV photopolymerization for production of synthetic hydrogel microspheres for cell encapsulation

Abstract

Microencapsulation within hydrogel microspheres holds much promise for drug and cell delivery applications. Synthetic hydrogels have many advantages over more commonly used natural materials such as alginate, however their use has been limited due to a lack of appropriate methods for manufacturing these microspheres under conditions compatible with sensitive proteins or cells. This study investigated the effect of flow rate and voltage on size and uniformity of the hydrogel microspheres produced via submerged electrospray combined with UV photopolymerization. In addition, the mechanical properties and cell survival within microspheres was studied. A poly(vinyl alcohol) (PVA) macromer solution was sprayed in sunflower oil under flow rates between 1-100 µL/min and voltages 0-10 kV. The modes of spraying observed were similar to those previously reported for electrospraying in air. Spheres produced were smaller for lower flow rates and higher voltages and mean size could be tailored from 50 to 1,500 µm. The microspheres exhibited a smooth, spherical morphology, did not aggregate and the compressive modulus of the spheres (350 kPa) was equivalent to bulk PVA (312 kPa). Finally, L929 fibroblasts were encapsulated within PVA microspheres and showed viability >90% after 24 h. This process shows great promise for the production of synthetic hydrogel microspheres, and specifically supports encapsulation of cells.

Poly(vinyl alcohol)-heparin biosynthetic microspheres produced by microfluidics and ultraviolet photopolymerisation

“…17 UV polymerisation is a common method for encapsulating cells in bulk gels and has been used with many cell types including chondrocytes 49 and mesenchymal stem cells 50 with high viability. Additionally, L929 fibroblasts that were encapsulated in the same PVA microspheres produced by a UV photopolymerisation and electrospray method also had >90% viability at 24 h. 8 Heparin has been incorporated into bulk hydrogels for the purpose of sustained growth factor release and presentation to cells and was shown to have beneficial effects on viability. 51 Therefore, it is likely that the heparin in the gels in the current study acts as a reservoir for growth factors present in the media (from the FBS) or released by the cells in the gel and helps to present these to the cells and in this way helps to sustain the viability.…”

“…More recently, Young et al have reported on a novel electrospray method for producing synthetic hydrogel microspheres. 8 However the major issue with these techniques is the polydispersity of microspheres produced. Minimising the sphere polydispersity is particularly important for cell microencapsulation applications as size uniformity supports more controlled and predictable mass transport properties within the spheres, which is extremely important for cell function within the transplanted microspheres.…”

Surface tension effects on submerged electrosprays

“…28 This last approach has recently yield cell viability of more than 90% when combined with UV photopolimerization for cell encapsulation. 29 Regardless of the good perspective, most the authors report a lack of stability in the submerged electrospray when compared with the high stability and reproducibility of their counterparts in air. Quite often the solutions employed require stabilizing agents as surfactants.…”

Injectable PEGylated fibrinogen cell-laden microparticles made with a continuous solvent- and oil-free preparation method

“…Several parameters of this system were varied to 39 control the size and polydispersity of the microparticles, including the cell density, the flow rate and 40 the air pressure in the nozzle. The system was capable of producing cell-laden microparticles with an 41 average diameter of between 88.1 to 347.1 lm, and a dispersity of between 1.1 and 2.4, depending on 42 the parameters chosen. Varying the precursor flow rate and/or cell density was beneficial in controlling 43 the size and polydispersity of the microparticles; all microparticles exhibited very high cell viability, 44 which was not affected by these parameters.…”