3D culture of ovarian follicles in granular and nanofibrillar hydrogels

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  • Marko Mihajlovic
  • Dóra Katalin Pásztor-Jánoska
  • Jesús Cadenas
  • Cristina Subiran Adrados
  • tcg964, tcg964
  • Stine Gry Kristensen
  • Johan Ulrik Lind
3D culture of ovarian follicles in hydrogel matrices is an important emerging tool for basic scientific studies as well as clinical applications such as fertility preservation. For optimizing and scaling 3D culture of preantral follicles, there is a need for identifying biomaterial matrices that simplifies and improves the current culture procedures. At present, microencapsulation of follicles in alginate beads is the most commonly used approach. However, this technique involves notable manual handling and is best suited for encapsulation of single or several follicles. As a potential alternative, we here explore the suitability of different particle-based hydrogel matrices, where follicles can easily be introduced in tunable 3D environments, in large numbers. Specifically, we study the growth of secondary murine follicles in microgranular alginate and nanofibrillar cellulose matrices, with and without cell-binding cues, and map follicle growth against the viscoelastic properties of the matrices. We cultured follicles within the particle-based hydrogels for 10 days and continuously monitored their size, survival, and tendency to extrude oocytes. Interestingly, we observed that the diameter of the growing follicles increased significantly in the particle-based matrices, as compared to state-of-the-art alginate micro-encapsulation. On the other hand, the follicles displayed an increased tendency for early oocyte extrusion in the granular matrices, leading to a notable reduction in the number of intact follicles. We propose that this may be caused by impaired diffusion of nutrients and oxygen through thicker matrices, attributable to our experimental setup. Still, our findings suggest that viscoelastic, granular hydrogels represent promising matrices for 3D culture of early-stage ovarian follicles. In particular, these materials may easily be implemented in advanced culturing devices such as micro-perfusion systems.
OriginalsprogEngelsk
Artikelnummer213987
TidsskriftBiomaterials Advances
Vol/bind164
Antal sider12
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
Johan Ulrik Lind reports financial support was provided by the Technical University of Denmark. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.M.M and J.U.L gratefully acknowledge support from the Independent Research fund Denmark (1032-00435B). J.C. C.S.A, C.Y.A and S.G.K gratefully acknowledge support from European Union Horizon 2020 programme under the Marie Sk\u0142odowska-Curie (860960), the Interregional EU collaboration ReproUnion 2.0, (20201846) as well as the Independent Research fund Denmark (10.46540/2096-00060B).

Funding Information:
M.M and J.U.L gratefully acknowledge support from the Independent Research fund Denmark ( 1032-00435B ). J.C., C.S.A, C.Y.A and S.G.K gratefully acknowledge support from European Union Horizon 2020 programme under the Marie Sk\u0142odowska-Curie ( 860960 ), the I nterregional EU collaboration ReproUnion 2.0 , ( 20201846 ) as well as the Independent Research fund Denmark ( 10.46540/2096-00060B ).

Publisher Copyright:
© 2024 The Authors

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