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

• Published in: Advanced functional materials 2023-08, Vol.33 (35), p.n/a
• Main Authors: Xue, Wen, Lee, Donghee, Kong, Yunfan, Kuss, Mitchell, Huang, Ying, Kim, Taesung, Chung, Soonkyu, Dudley, Andrew T., Ro, Seung‐Hyun, Duan, Bin
• Format: Article
• Language: English
• Subjects: adipose‐cancer interaction; Alginates; Calcium ions; core‐shell; Current carriers; Emulsions; Hydrogels; Materials science; porous hydrogels; Spheroids; two‐phase aqueous emulsions
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202214129

Porous alginate (Alg) 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 Alg hydrogels based on two‐phase aqueous emulsions is reported. The pre‐gel solutions, which contain two immiscible aqueous phases of Alg and caseinate (Cas), are cross‐linked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the Cas phase from the ion‐cross‐linked Alg hydrogel. Those porous Alg hydrogels possess heterogeneous pores ≈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 Alg 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 Alg hydrogels for applications as cell carriers and in disease modeling. A simple and biocompatible approach to generate porous cell‐laden alginate (Alg) hydrogels based on two‐phase aqueous emulsions is developed. The heterogeneous pores, interconnected paths, and bioinert matrix of porous Alg hydrogels facilitate encapsulated cell survival, proliferation, in situ spheroid organization, and differentiation. This study also provides a feasible platform to investigate adipocyte and cancer cell crosstalk.