A novel fibrin-based artificial ovary prototype resembling human ovarian tissue in terms of architecture and rigidity
The aim of this study is to optimize fibrin matrix composition in order to mimic human ovarian tissue architecture for human ovarian follicle encapsulation and grafting.
Ultrastructure of fresh human ovarian cortex in age-related women (n = 3) and different fibrin formulations (F12.5/T1, F30/T50, F50/T50, F75/T75), rheology of fibrin matrices and histology of isolated and encapsulated human ovarian follicles in these matrices.
Fresh human ovarian cortex showed a highly fibrous and structurally inhomogeneous architecture in three age-related patients, but the mean ± SD of fiber thickness (61.3 to 72.4 nm) was comparable between patients. When the fiber thickness of four different fibrin formulations was compared with human ovarian cortex, F50/T50 and F75/T75 showed similar fiber diameters to native tissue, while F12.5/T1 was significantly different (p value < 0.01). In addition, increased concentrations of fibrin exhibited enhanced storage modulus with F50/T50, resembling physiological ovarian rigidity. Excluding F12.5/T1 from further analysis, only three remaining fibrin matrices (F30/T50, F50/T50, F75/T75) were histologically investigated. For this, frozen-thawed fragments of human ovarian tissue collected from 22 patients were used to isolate ovarian follicles and encapsulate them in the three fibrin formulations. All three yielded similar follicle recovery and loss rates soon after encapsulation. Therefore, based on fiber thickness, porosity, and rigidity, we selected F50/T50 as the fibrin formulation that best mimics native tissue.
Of all the different fibrin matrix concentrations tested, F50/T50 emerged as the combination of choice in terms of ultrastructure and rigidity, most closely resembling human ovarian cortex.
KeywordsHuman ovarian tissue microstructure Scanning electron microscopy Fibrin matrix Porosity Isolated follicles Artificial ovary
The authors thank Patricia Meijers for her collaboration and scientific advice on fibrin in the project. They also thank Mira Hryniuk, BA, for reviewing the English language of the manuscript and Delphine Magnin, Dolores Gonzalez, and Olivier Van Kerk for their technical assistance. This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS) awarded to C. A. Amorim as a research associate for the FRS-FNRS and M.M. Dolmans (grant 5/4/150/5), Fonds Spéciaux de Recherche, Fondation St Luc, Foundation Against Cancer, and Wallonie-Bruxelles International, and donations from the Ferrero family.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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