A blueprint of the topology and mechanics of the human ovary for next-generation bioengineering and diagnosis

Abstract

Although the first dissection of the human ovary dates back to the 17th century, the biophysical characteristics of the ovarian cell microenvironment are still poorly understood. However, this information is vital to deciphering cellular processes such as proliferation, morphology and differentiation, as well as pathologies like tumor progression, as demonstrated in other biological tissues. Here, we provide the first readout of human ovarian fiber morphology, interstitial and perifollicular fiber orientation, pore geometry, topography and surface roughness, and elastic and viscoelastic properties. By determining differences between healthy prepubertal, reproductive-age, and menopausal ovarian tissue, we unravel and elucidate a unique biophysical phenotype of reproductive-age tissue, bridging biophysics and female fertility. While these data enable to design of more biomimetic scaffolds for the tissue-engineered ovary, our analysis pipeline is applicable for the characterization of other organs in physiological or pathological states to reveal their biophysical markers or design their bioinspired analogs.

Spatio-temporal remodelling of the composition and architecture of the human ovarian cortical extracellular matrix duringin vitroculture

“…Cortical sub-regions are also characterized by different patterns of collagen fibres in terms of thickness and packing, density, width, length, straightness and alignment. Comparable collagen fibre thickness, straightness coefficient, and angle have been previously reported in ovaries of reproductive-aged women (Ouni et al, 2020(Ouni et al, , 2021. These compartmental differences within the cortex may be functional, likely conferring the tissue with distinct regional mechanical properties.…”

When Electrospun Fiber Support Matters: In Vitro Ovine Long-Term Folliculogenesis on Poly (Epsilon Caprolactone) (PCL)-Patterned Fibers

“…Within this framework, the present work aimed to highlight the pivotal role of biomaterial properties and the related follicle–biomaterial interactions in an in vitro developmental context, comparing the results to a previously validated approach [ 14 , 86 ] and focusing attention on the electrospinning technique for fiber fabrications, which previously has been shown to be an appropriate technique to obtain a fibrillary morphology similar to the native ovarian cortex in a porcine model [ 35 , 36 , 79 ]. Moreover, the relevance of the fiber structure in the human ovary has been highlighted in recent work by Ouni et al [ 92 ]. Likewise, poly (epsilon-caprolactone) (PCL)-based electrospun randomic and patterned scaffolds were investigated as support for ovine preantral follicles in vitro development, evaluating the follicular and oocyte performance in terms of follicle and oocyte growth, as well as the follicle capability to develop antrum cavity, gene expression profile, and the achievement of oocyte meiotic competence.…”

Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling

“…A big advantage of using in vitro systems is that they may increase experimental variable control while maintaining physiologically relevant qualities, which is a substantial advantage. Most often utilized in vitro cancer models in the past were tumor-derived cell lines that had been immortalized histopathologically and grown as adherent 2D cultures [123,124]. They can also be used to do fast drug testing owing of their broad availability and ease of upkeep.…”