Tuneable spheroidal hydrogel particles for cell and drug encapsulation

Abstract

The need to better mimic native tissues has accompanied research in tissue engineering and controlled drug delivery. The development of new platforms for cell and drug encapsulation followed the same trend, and studying the influence of the delivery material system's geometry has been gaining momentum. Aiming to investigate how an increase in surface area and varying particle shape could impact drug release and cell viability, a novel method was developed to produce spheroidal hydrogel particles with adjustable circularity, aiming to tune drug delivery. For this purpose, droplets of hydrogel precursor were squeezed between two superamphiphobic surfaces separated with spacers with different height, and then photo-crosslinked to maintain the acquired shape after "de-sandwiching". Numerical modelling studies were performed to study the polymeric droplet geometry deformation process, which were consistent with experimentally obtained results. The spheroidal particles were produced under mild conditions using methacrylated chitosan, capable of encapsulating proteins or cells. Likely due to their higher surface area to volume-ratio, compared to spherical-shaped ones, spheroids presented an improved viability of encapsulated cells due to enhanced nutrient diffusion to the core, and led to a significantly faster drug release rate from the polymer network. These results were also assessed numerically, in which the drug release rate was computed for different spheroidal-like geometries. Hence, the described method can be used to manufacture spheroidal particles with tailored geometry that can be broadly applied in the biomedical field, including for drug delivery or as cell encapsulation platforms.

Hybrid hydrogels for biomedical applications

“…One such example is the potential of using spheroid particles generated by squeezing chitosan droplets between two superamphiphobic surfaces, followed by UV-crosslinking, to increase the release rate of encapsulated BSA. BSA was encapsulated in the particles and faster release was observed from spheroids than from spheres, shown in Figure 3 [64].…”

“…The benefits of anisotropic microparticles, such as spheroids, ellipsoids, rods, and disks, also have been shown to extend to hemodynamic settings, with both theoretical modeling and experimental studies indicating better margination, wall interaction, and adhesion [65]. The enhancement of both diffusion and cell viability (demonstrated by the incorporation of spheroid particles) [64], as well as the potential hemodynamic transport benefits arising from anisotropic particles, suggests the potential of employing more complex and anisotropic particles in hybrid hydrogels. Non-circular micropatterned regions in hybrid hydrogels have also been shown to increase the absorption of toxins, thus increasing the detoxification efficacy of these materials [66].…”

“…However, the ability to tune the release from and into micro-domains is constrained due to geometry. With increased particle diameter, diffusion is limited as spheres possess a lower surface area to volume ratio [64]. In order to account for this shortcoming, particles of different geometries can be made to enable increased surface area and a correspondingly increased range in potential drug release rates.…”

“…Variation in height of spheroidal particles (¾, ½, and ¼) is presented relative to spherical particles, corresponding to 1. Adapted from Bjørge et.al[64]. (Reproduced with permission from the Royal Society of Chemistry, Copyright 2018.)…”

Protein: a versatile biopolymer for the fabrication of smart materials for drug delivery

“…These results were also assessed numerically, in which the drug release rate was computed for different spheroidal-like geometries. 43 In another study, Wang et al, discovered the effect of applied voltage, on the morphology of electrospun zein protein fabrics. They reported that these protein fabrics formed either flat sheets or self-rolled tubes when immersed in water on the application of different voltage.…”