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Considerable challenges in engineering the female reproductive tissue are the follicle's 25 unique architecture, the need to recapitulate the extracellular matrix, and tissue 26 vascularization. Over the years, various strategies have been developed for preserving 27 fertility in women diagnosed with cancer, such as embryo, oocyte, or ovarian tissue 28 cryopreservation. While autotransplantation of cryopreserved ovarian tissue is a viable 29 choice to restore fertility in prepubertal girls and women who need to begin chemo-or 30 radiotherapy soon after the cancer diagnosis, it is not suitable for all patients due to the risk 31 of having malignant cells present in the ovarian fragments in some types of cancer. Advances 32 in tissue engineering such as 3D printing and ovary-on-a-chip technologies have the 33 potential to be a translational strategy for precisely recapitulating normal tissue in terms of 34 physical structure, vascularization, and molecular and cellular spatial distribution. This 35 review first introduces the ovarian tissue structure, describes suitable properties of 36 biomaterials for ovarian tissue engineering, and highlights recent advances in tissue 37 engineering for developing an artificial ovary. 38 39 40 Keywords 41 Ovarian tissue engineering; follicle; in vitro culture; 3D printing; ovary-on-a-chip 42 157 9 Ovarian cells can be added to the isolated follicles to support their development 158 during in vitro culture or transplantation. These cells secrete autocrine/paracrine 159 factors involved in folliculogenesis [44], and some of them will be recruited by 160 growing follicles to differentiate into theca cells [48]. Moreover, to improve follicle 161 survival, one could play with the biomaterial used as a scaffold, its porosity, 162 mechanical strength, and bioactive sites, as well as the addition of hormones, growth 163 factors, etc. [8, 11, 49-53]. For instance, to enhance vascularization, follicles could be 164 encapsulated in biomaterials with sustained release of vascular endothelial growth 165 factor (VEGF) [54] or basic fibroblast growth factor (bFGF) [55]. 166 167 4 Development of follicle culture systems 168The 2D in vitro system has been routinely used for follicle' in vitro culture [56][57][58][59][60][61]. Several 169 approaches, such as multi-well plates, cell culture dishes, or coverslips coated by gels or ECM 170 proteins such as collagen, fibronectin, and laminin, have been used in this procedure [3, 33, 171 62]. When isolated follicles are attached to a 2D culture surface, the somatic cells migrate to 172 the bottom of the well, gradually losing their interaction with the oocyte, and consequently, 173 the follicle 3D structure is destroyed [7]. Indeed, 2D culture systems are different from in 174 vivo microenvironment conditions, where cells and tissues have complex connections with 709This study was supported by grants from the Fonds National de la Recherche Scientifique de 710 Belgique (the Excellence of Science (FNRS-EOS), number 30443682 (PhD scholarship 711 award...

Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently, COVID-19. However, DEX usage is often restricted in the clinic due to its poor water solubility. When administered through a systemic route, it can elicit severe side effects, such as hypertension, peptic ulcers, hyperglycemia, and hydro-electrolytic disorders. There is currently much interest in developing efficient DEX-loaded nanoformulations that ameliorate adverse disease effects inhibiting advancements in scientific research. Various nanoparticles have been developed to selectively deliver drugs without destroying healthy cells or organs in recent years. In the present review, we have summarized some of the most attractive applications of DEX-loaded delivery systems, including liposomes, polymers, hydrogels, nanofibers, silica, calcium phosphate, and hydroxyapatite. This review provides our readers with a broad spectrum of nanomedicine approaches to deliver DEX safely.

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An artificial ovary is a promising approach for preserving fertility in prepubertal girls and women who cannot undergo current cryopreservation strategies. However, this approach is in its infancy, due to the possible challenges of creating a suitable 3D matrix for encapsulating ovarian follicles and stromal cells. To maintain the ovarian stromal cell viability and proliferation, as a first step towards developing an artificial ovary, in this study, a double network hydrogel with a high water swelling capacity (swelling index 15–19) was developed, based on phenol conjugated chitosan (Cs-Ph) and silk fibroin (SF) through an enzymatic crosslinking method using horseradish peroxidase. The addition of SF (1%) to Cs (1%) decreased the storage modulus (G’) from 3500 Pa (Cs1) to 1600 Pa (Cs-SF1), and the hydrogels with a rapid gelation kinetic produced a spatially homogeneous distribution of ovarian cells that demonstrated 167% proliferation after 7 days. This new Cs-SF hydrogel benefits from the toughness and flexibility of SF, and phenolic chemistry could provide the potential microstructure for encapsulating human ovarian stromal cells.

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