Single-Step Synthesis of Alginate Microgels Enveloped with a Covalent Polymeric Shell: A Simple Way to Protect Encapsulated Cells

Abstract

Microgels of biopolymers such as alginate are widely used to encapsulate cells and other biological payloads. Alginate is an attractive material for cell encapsulation because it is nontoxic and convenient: spherical alginate gels are easily created by contacting aqueous droplets of sodium alginate with divalent cations such as Ca2+. Alginate chains in the gel become cross-linked by Ca2+ cations into a 3-D network. When alginate gels are placed in a buffer, however, the Ca2+ cross-links are eliminated by exchange with Na+, thereby weakening and degrading the gels. With time, encapsulated cells are released into the external solution. Here, we describe a simple solution to the above problem, which involves forming alginate gels enveloped by a thin shell of a covalently cross-linked gel. The shell is formed via free-radical polymerization using conventional monomers such as acrylamide (AAm) or acrylate derivatives, including polyethylene glycol diacrylate (PEGDA). The entire process is performed in a single step at room temperature (or 37 °C) under mild, aqueous conditions. It involves combining the alginate solution with a radical initiator, which is then introduced as droplets into a reservoir containing Ca2+ and monomers. Within minutes of either simple incubation or exposure to ultraviolet (UV) light, the droplets are converted into alginate–polymer microcapsules with a core of alginate and a shell of the polymer (AAm or PEGDA). The microcapsules are mechanically more robust than conventional alginate/Ca2+ microgels, and while the latter swell and degrade when placed in buffers or in chelators like sodium citrate, the former remain stable under all conditions. We encapsulate both bacteria and mammalian cells in these microcapsules and find that the cells remain viable and functional over time. Lastly, a variation of the synthesis technique is shown to generate multilayered microcapsules with a liquid core surrounded by concentric layers of alginate and AAm gels. We anticipate that the approaches presented here will find application in a variety of areas including cell therapies, artificial cells, drug delivery, and tissue engineering.

Cell‐Like Capsules with “Smart” Compartments

“…Because this layer is formed by covalent bonds, it makes the construct robust and allows it to survive the degradation steps. [ 29,30 ]…”

Alginate-Based Applications in Biotechnology with a Special Mention to Biosensors

“…Preparation of alginate composite with such hetero functionalities holds the prospect for exponential advancement of the application of alginate in industrial, biotechnological, and medical contexts. Thus, alginate and its derived composites hold a high prospect for the co-immobilisation and co-localisation of cells [175]…”

Improved Osteogenesis by Mineralization Combined With Double-Crosslinked Hydrogel Coating for Proliferation and Differentiation of Mesenchymal Stem Cells

“…Except for good biocompatibility and mimicking natural extracellular matrices, hydrogel was found to be the superior carrier for growth factors ( Liang et al, 2020 ). Alginate, a natural polymer, includes (1-4)-linked b-D-mannuronic acid and a-L-guluronic acid with good biocompatibility ( Drury et al, 2004 ; Ahn et al, 2021 ). With the participation of divalent cations (e.g., Ca 2+ ), rapid ionic crosslinking can be achieved in sodium alginate ( Ahn et al, 2021 ).…”

“…Alginate, a natural polymer, includes (1-4)-linked b-D-mannuronic acid and a-L-guluronic acid with good biocompatibility ( Drury et al, 2004 ; Ahn et al, 2021 ). With the participation of divalent cations (e.g., Ca 2+ ), rapid ionic crosslinking can be achieved in sodium alginate ( Ahn et al, 2021 ). Sodium alginate has been approved by the U.S. Food and Drug Administration (FDA) for medical use, because there is no toxic medium in the sodium alginate gel preparation process ( Wang et al, 2020 ).…”