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A Facile Strategy for the Fabrication of Cell‐Laden Porous Alginate Hydrogels based on Two‐Phase Aqueous Emulsions

Wen XueCollege of Biological Science and Medical Engineering Donghua University Shanghai 201620 ChinaDong-Hee LeeDepartment of Surgery University of Nebraska Medical Center Omaha NE 68198 USAYunfan KongDepartment of Internal Medicine University of Nebraska Medical Center Omaha NE 68198 USAMitchell KussDepartment of Internal Medicine University of Nebraska Medical Center Omaha NE 68198 USAYing HuangEppley Institute for Research in Cancer and Allied Diseases University of Nebraska Medical Center Omaha NE 68198 USATaesung KimDepartment of Biochemistry and the Redox Biology Center University of Nebraska‐Lincoln Lincoln NE 68588 USASoonkyu ChungDepartment of Nutrition University of Massachusetts Amherst Amherst MA 01003 USAAndrew T. DudleyDepartment of Genetics University of Nebraska Medical Center Omaha NE 68198 USASeung‐Hyun RoDepartment of Biochemistry and the Redox Biology Center University of Nebraska‐Lincoln Lincoln NE 68588 USABin DuanDepartment of Internal Medicine University of Nebraska Medical Center Omaha NE 68198 USA
2023en
ABI

Abstract

Porous alginate hydrogels possess many advantages as cell carriers. However, current pore generation methods require either complex or harsh fabrication processes, toxic components, or extra purification steps, limiting the feasibility and affecting the cellular survival and function. In this study, a simple and cell-friendly approach to generate highly porous cell-laden alginate hydrogels based on two-phase aqueous emulsions is reported. The pre-gel solutions, which contain two immiscible aqueous phases of alginate and caseinate, are crosslinked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the caseinate phase from the ion-crosslinked alginate hydrogel. Those porous alginate hydrogels possess heterogeneous pores around 100 μm and interconnected paths. Human white adipose progenitors (WAPs) encapsulated in these hydrogels self-organize into spheroids and show enhanced viability, proliferation, and adipogenic differentiation, compared to non-porous constructs. As a proof of concept, this porous alginate hydrogel platform is employed to prepare core-shell spheres for coculture of WAPs and colon cancer cells, with WAP clusters distributed around cancer cell aggregates, to investigate cellular crosstalk. This efficacious approach is believed to provide a robust and versatile platform for engineering porous-structured alginate hydrogels for applications as cell carriers and in disease modeling.

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