Generation of Gellan Gum-Based Adipose-Like Microtissues

Abstract

Adipose tissue is involved in many physiological processes. Therefore, the need for adipose tissue-like analogues either for soft tissue reconstruction or as in vitro testing platforms is undeniable. In this work, we explored the natural features of gellan gum (GG) to recreate injectable stable adipose-like microtissues. GG hydrogel particles with different percentages of polymer (0.5%, 0.75%, 1.25%) were developed and the effect of obtained mechanical properties over the ability of hASCs to differentiate towards the adipogenic lineage was evaluated based on the expression of the early (PPARγ) and late (FABP4) adipogenic markers, and on lipids formation and accumulation. Constructs were cultured in adipogenic induction medium up to 21 days or for six days in induction plus nine days in maintenance media. Overall, no significant differences were observed in terms of hASCs adipogenic differentiation within the range of Young’s moduli between 2.7 and 12.9 kPa. The long-term (up to six weeks) stability of the developed constructs supported its application in soft tissue reconstruction. Moreover, their ability to function as adipose-like microtissue models for drug screening was demonstrated by confirming its sensitivity to TNFα and ROCK inhibitor, respectively involved in the repression and induction of the adipogenic differentiation.

High-throughput fabrication of cell-laden 3D biomaterial gradients

“…1) for the chondrogenic differentiation. In regards to the PPAR-γ responses, the observed trend, overall slight yet detectable, also supports previous results concerning the adipogenic differentiation in soft GG hydrogels 27 .…”

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

“…In sum, all suggest that GG is a suitable material for encapsulation, adipogenic differentiation, and maintenance of human primary ASCs. This was also demonstrated by another study which has shown the development of adipose-like microtissues based on GG [61]. Like us, they have shown successful adipogenic differentiation of encapsulated ASCs in different GG concentrations.…”

Construction of vascularized tissue-engineered breast with dual angiogenic and adipogenic micro-tissues

“…Micro-tissues engineering for adipose/breast have been explored by several groups. Most of them constructed adipose-like micro-tissues in vitro [ [19] , [45] ]. Hoefner, C cultured self-assembly ADSC spheroids using the liquid overlay technique and evaluated the ECM of differentiated ADSC spheroids, which was proved to be similar to native adipose [ 17 ].…”

“…Hoefner, C and co-workers cultured ADSCs spheroids and found that their ECM mainly consisted of fibronectin, collagen V, and VI and shifted into laminin, collagen I, IV, V and VI after adipogenic induction in vitro, like ECM in native adipose tissue [ 17 ]. Some ADSCs micro-tissues were fabricated and lipid accumulation were observed in vitro [ [18] , [19] , [20] ]. However, when it comes to animal experiments, single adipose micro-tissues are easy to result in adipose tissue atrophy and fibrosis due to insufficient vascularization [ 18 ].…”