Production of hyaluronic‐acid‐based cell‐enclosing microparticles and microcapsules via enzymatic reaction using a microfluidic system

Abstract

This article describes the preparation of cell-enclosing hyaluronic acid (HA) microparticles with solid core and microcapsules with liquid core through cell-friendly horseradish peroxidase (HRP)-catalyzed hydrogelation. The spherical vehicles were made from HA derivative possessing phenolic hydroxyl moieties (HA-Ph) cross-linkable through the enzymatic reaction by extruding cellsuspending HA-Ph aqueous solution containing HRP from a needle of 180 lm in inner diameter into the ambient coaxial flow of liquid paraffin containing H 2 O 2 in a microtubule of 600 lm in diameter. By altering the flow rate of liquid paraffin, the diameters of gelatin and HA-Ph microparticles were varied in the range of 120-220 lm and 100-300 lm, respectively. The viability of the enclosed human hepatoma HepG2 cells in the HA-Ph microparticles of 180 lm in diameter was 94.2 6 2.3%. The growth of the enclosed HepG2 cells was enhanced by decreasing the HRP concentration. The microcapsules of 200 lm in diameter were obtained by extruding HA-Ph aqueous solution containing thermally liquefiable cell-enclosing gelatin microparticles of 150 lm in diameter using the same microfluidic system. The enclosed cells grew and filled the cavity within 10 days. Spherical tissues covered with a heterogeneous cell layer were obtained by degrading the microcapsule membrane using hyaluronidase after covering the surface with a heterogeneous cell layer.

TEMPO-Nanocellulose/Ca2+ Hydrogels: Ibuprofen Drug Diffusion and In Vitro Cytocompatibility

“…Three-dimensional cell culture in hydrogels has become an outstanding tool both for the fabrication of tissue engineered scaffolds [6] and for the development of 3D in vitro models [7]. The versatility of hydrogels allows for their fabrication, with embedded cells, by different technologies, including wet spinning [8], 3D printing [9], microspheres [10], and microfluidics [11]. In particular, injectable hydrogels have recently been gaining increasing interest regarding the localized introduction of small functional molecules for diagnostic purposes [12], for drug release and delivery [13] or injection of stem cells in regenerative therapy [14,15].…”

Biopolymer Microparticles Prepared by Microfluidics for Biomedical Applications

“…The MSCs also maintained viability after long term culture up to 4 weeks and exhibited the multipotency and differentiation potential upon induction (Figure C). Another derivate of HA with phenolic hydroxyl moieties (HA‐Ph) was also used to fabricate HA MPs via cell‐friendly horseradish peroxidase (HRP)‐catalyzed oxidative crosslinking for cell encapsulation . The HRP enzyme catalyzes the crosslinking of phenolic hydroxyl moieties using hydrogen peroxide (H 2 O 2 ) as an electron donor .…”

“…Another derivate of HA with phenolic hydroxyl moieties (HA-Ph) was also used to fabricate HA MPs via cell-friendly horseradish peroxidase (HRP)-catalyzed oxidative crosslinking for cell encapsulation. [112] The HRP enzyme catalyzes the crosslinking of phenolic hydroxyl moieties using hydrogen peroxide (H 2 O 2 ) as an electron donor. [113] The human hepatocyte (HepG2)-laden HA-Ph microspheres showed ≈94% of viability.…”

Microfluidic technologies to engineer mesenchymal stem cell aggregates—applications and benefits

“…The focus of many studies is on incorporating various hydrogels for the generation of microgel structures that could be solid spheres, hard shell and soft core, and hollow type microgels (Ashida et al, 2013;Sakai et al, 2014;Khanmohammadi et al, 2016). Multicellular aggregates encapsulated within microgels serve as bioinks inducing (Pajoumshariati et al, 2018;Chen et al, 2019b;Abdulghani and Morouço, 2019).…”