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The proportion of cancer patients that survive is increasing because of improvements in cancer therapy. However, some cancer treatments, such as chemo- and radio-therapies, can cause considerable damage to reproductive function. The issue of fertility is paramount for women of childbearing age once they are cured from cancer. For those patients with prepubertal or haematogenous cancer, the possibilities of conventional fertility treatments, such as oocyte or embryo cryopreservation and transplantation, are limited. Moreover, ovarian tissue cryopreservation as an alternative to fertility preservation has limitations, with a risk of re-implanting malignant cells in patients who have recovered from potentially fatal malignant disease. One possible way to restore fertility in these patients is to mimic artificially the function of the natural organ, the ovary, by grafting isolated follicles embedded in a biological scaffold to their native environment. Construction and cryopreservation of an artificial ovary might offer a safer alternative option to restore fertility for those who cannot benefit from traditional fertility preservation techniques. This review considers the protocols for constructing an artificial ovary, summarises advances in the field with potential clinical application, and discusses future trends for cryopreservation of these artificial constructions.

Reproduction is the most important event for the continuation of life. Unfortunately, infertility is a widespread problem. Recently, biomaterials have been widely used in reproductive biology, including tissue engineering, regenerative medicine and contraception. In this review, we summarize the research progress of biomaterials applied in follicle culture, artificial ovary, tissue engineering, and contraception. We first introduce the applications and advantages of different biomaterials in follicle culture and artificial ovary. Then, we summarize the biomaterials for tissue engineering in reproductive biology. Also, we introduce the applications of biomaterials for contraception. Besides, some emerging technologies are also introduced, such as microfluidic chip, organ chip, 3D printing, electrostatic spinning and stem cell therapy in the fundamental research and clinical application. We believe that this review will promote the interdisciplinary communication between biomaterial science and reproductive biology.

The ovarian reserve (OR) indicates ovarian function by representing the quantity and quality of ovarian follicles, and it gradually decreases with increasing age. With the prolongation of women’s lives, the protection provided by estrogen is lost for decades in postmenopausal women, and the related cardiovascular and cerebrovascular diseases, osteoporosis, and decreased immunity are the main risk factors affecting women’s quality of life and longevity. Pharmacologic hormone replacement therapy (PHRT) has been controversial, and the construction of artificial ovary (AO) has attracted increasing attention. The most critical step of AO generation is the establishment of an in vitro culture (IVC) system to support the development of isolated follicles. This article mainly compares the advantages and disadvantages of different polymer biomaterials for use in follicle IVC, provides theoretical support for the development and construction of the follicle IVC system using natural biological materials, and provides a theoretical basis for establishing mature AO technology.

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

Background The aim of this study was to examine the effectiveness of Tumor Dissociation Enzyme (TDE) on the viability of follicles after digestion of fresh and cryopreserved ovarian cortex fragments (OCFs). Methods Fresh and thawed OCF from 14 patients (29 ± 6 years), sized 20 to 210 mm3 were randomly distributed into four treatment groups and digested with 16% TDE or 0.05 mg/ml Liberase TM: Group 1, frozen OCF digested with TDE; Group 2, frozen OCF digested with LiberaseTM; Group 3, fresh OCF digested with TDE; and Group 4, fresh OCF digested with Liberase TM. Evaluation of follicle viability was performed under light microscope after staining with Neutral red. For visualization of viable and dead cells under a confocal laser scanning microscope, the follicles were stained with Calcein AM and ethidium homodimer-1. Results The results showed that the number of retrieved follicles was significantly higher (990 vs 487; P

PURPOSE: To evaluate the tumor-inducing ability of a few leukemic cells xenotransplanted inside an artificial ovary. METHODS: Ten and 100 BV-173 leukemic cells were embedded in a fibrin matrix along with 50,000 human ovarian stromal cells, and grafted to the peritoneal bursa of 5 and 5 SCID mice respectively. Four mice grafted with 3x10(6) leukemic cells in fibrin served as positive controls. At 20 weeks post-transplantation, the grafts, liver, spleen, blood and bone marrow were analyzed for the presence of leukemia by anti-CD79α IHC, flow cytometry (FC) and PCR. RESULTS: All mice grafted with 3x10(6) cells developed peritoneal masses 4 weeks after xenotransplantation, and systemic disease was confirmed by IHC, PCR and FC. Among mice grafted with 10 or 100 leukemic cells, none showed any sign of leukemia after 20 weeks, and IHC, FC and PCR on the different recovered tissues all proved negative. CONCLUSION: This study investigates the tumor-inducing potential of a few leukemic cells grafted inside an artificial ovary. Transplantation of 100 leukemic cells appears to be insufficient to induce leukemia after 20 weeks. These results in an immunodeficient xenografting model are quite reassuring. However, for clinical application, follicle suspensions must be purged of leukemic cells before grafting, as even the slightest risk should be avoided.