Gellan Gum Is a Suitable Biomaterial for Manual and Bioprinted Setup of Long-Term Stable, Functional 3D-Adipose Tissue Models

Abstract

Due to its wide-ranging endocrine functions, adipose tissue influences the whole body’s metabolism. Engineering long-term stable and functional human adipose tissue is still challenging due to the limited availability of suitable biomaterials and adequate cell maturation. We used gellan gum (GG) to create manual and bioprinted adipose tissue models because of its similarities to the native extracellular matrix and its easily tunable properties. Gellan gum itself was neither toxic nor monocyte activating. The resulting hydrogels exhibited suitable viscoelastic properties for soft tissues and were stable for 98 days in vitro. Encapsulated human primary adipose-derived stem cells (ASCs) were adipogenically differentiated for 14 days and matured for an additional 84 days. Live-dead staining showed that encapsulated cells stayed viable until day 98, while intracellular lipid staining showed an increase over time and a differentiation rate of 76% between days 28 and 56. After 4 weeks of culture, adipocytes had a univacuolar morphology, expressed perilipin A, and secreted up to 73% more leptin. After bioprinting establishment, we demonstrated that the cells in printed hydrogels had high cell viability and exhibited an adipogenic phenotype and function. In summary, GG-based adipose tissue models show long-term stability and allow ASCs maturation into functional, univacuolar adipocytes.

Gums as Macromolecular Crowding Agents in Human Skin Fibroblast Cultures

“…Furter, the cytocompatibility of CR has been well-established in the literature [58,93] and has even been used effectively in clinical settings [94,95]. Similarly, all assessed gums are used extensively in the biomaterials field with an equal well-documented cytocompatibility (e.g., GA [96][97][98][99], GG [100][101][102][103][104], GK [105][106][107], GX [108][109][110]) with a diverse range of cell populations.…”

Biofabrication's Contribution to the Evolution of Cultured Meat

“…Albrecht et al developed a protocol allowing for long-term cell culture (up to 84 days after differentiation) of bioprinted adipose tissue constructs initially fabricated from an ASC-laden gellan gum bioink stabilized by calcium ions. [87] It was shown that matured ACs were repeatedly able to secret expected amounts of leptin over time and demonstrated tissue-like lipid formation.…”