Physical aspects of the artificial ovary : characterization of human ovarian tissue and fibrin scaffolds

While the number of girls and young women reached by cancer increases year upon year, improvements in cancer treatments allow to cure most of them. However, these treatments can result in premature ovarian failure. To solve this problem, several fertility preservation and restoration techniques are already available. Nevertheless, for patients at prepubertal stage or that cannot postpone their cancer treatment, cryopreservation and transplantation of ovarian tissue is the only available option. Eventhough this technique has shown to be successful, it is not advisable for patients with certain types of cancer, since there is a risk of reintroducing malignant cells present in the cryopreserved tissue, which could lead to the recurrence of the primary disease. For these patients, research teams worldwide have been working on the development of a transplantable artificial ovary, which consists in the encapsulation of isolated ovarian preantral follicles and cells by a 3D matrix. As this matrix should ideally mimic the natural human ovary, the goal of the present study is to characterize and compare the morphological and physical properties of both human ovary and the matrix that yielded best results so far, i.e., fibrin. To this end, samples of human ovarian cortex and different fibrin formulations (F12.5/T1, F30/T50, F50/T50 and F75/T75) were analyzed using a scanning electron microscope and a shear rheometer. According to these analyzes, the fibrin hydrogels made of 30 mg/ml fibrinogen and 50 U/ml thrombin showed to be the most similar to human ovarian tissue and therefore seem to be the best candidate to encapsulate isolated preantral follicles.Master [120] : ingénieur civil biomédical, Université catholique de Louvain, 201

A novel fibrin-based artificial ovary prototype resembling human ovarian tissue in terms of architecture and rigidity.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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