双光子三维打印蛋白微室对卵母细胞体外成熟的影响及其机制研究

As China adopted the second-child policy, the number of elderly parturient women has surged. These pregnant women are facing all kinds of risks of advanced child birth. The first and foremost is the deterioration of ovarian function. This leads to a lower quality or distortion of the oocyte; Other dominant risks include the decline of oocytes function and the incidence of chromosomal abnormalities, etc. Therefore, it has become an urgent challenge that how to extend the childbearing age of women and improve the fertility of this group of women in clinical and reproductive medical engineering. This project aims to tackle this challenge by developing and applying an advanced 3D biomedical printing technology. Combining the computer-aided design with the two-photon excitation photochemical crosslinking technology, the liquid protein cross-curing could be solidified into a very fine and freely regulated single-follicular 3D micron-sized protein chamber. With the nanoscale control accuracy, we can fabricate a new 3D culture system of single ovarian follicle culture. The microenvironment of such culture system can be tuned by changing the mechanical properties, biochemical composition or topological features of the protein chamber. In the further, this 3D culture system will be used for in-vitro maturation of immature oocyte. The output of this project can not only help reveal the intrinsic functions of the ovary and the development mechanism of ovarian follicles, but also facilitate the further investigation of the in vitro development and maturation of human oocytes.

随着国家二胎政策的开放，高龄产妇的现象越来越多，这类人群正面临高龄生育各方面的风险，首当其冲的是卵巢功能的退化，卵子质量降低，易出现畸变；以及卵细胞功能减退，染色体异常疾病的发生率增加等问题。因此如何延长女性的生育年龄，挽救上述群体女性的生育能力成为临床与生殖医学工程领域中非常重要的挑战。本项目通过计算机辅助设计，结合双光子激发光化学交联作用，使液态蛋白质交联固化成超精微可自由调控的单卵泡3D蛋白微室。在控制精度达到纳米级别的基础之上，通过改变蛋白微室的机械性能、生物化学成分、以及拓扑形态等特征对单个卵泡培养建立全新的立体包裹式三维培养体系，使未成熟卵母细胞在体外发育成熟至可受精阶段。这些研究不仅有助于揭示卵巢的内在机能和卵泡发展的机制，并且为进一步研究人类卵母细胞的体外发育及成熟提供有益的探索。

目前我国不孕不育患者人数已超过5000万，呈年轻化趋势，加之恶性肿瘤患者的日趋年轻化，手术、放疗、化疗等治疗均可导致严重的女性生殖系统损伤，生殖能力的下降，因此如何延长女性的生育年龄，挽救上述群体女性的生育能力成为临床与生殖医学工程领域中非常重要的挑战。卵母细胞体外成熟培养可以实现未成熟卵泡在体外的正常发育，并将获得的成熟卵母细胞与精子体外授精，这能够为解决上述医学难题提供有利的基础医学研究和临床价值。本项目通过计算机辅助设计，结合双光子激发光化学交联作用，使液态蛋白质交联固化成超精微可自由调控的单卵泡3D微米级蛋白小室。在控制精度达到纳米级别的基础之上，通过改变蛋白小室的机械性能、生物化学成分、以及拓扑形态等特征对单个卵泡培养建立全新的立体包裹式三维培养体系，使未成熟卵母细胞在体外发育成熟至可受精阶段。这些研究不仅有助于揭示卵巢的内在技能和卵泡发生发展的机制，并且为进一步研究人类卵母细胞的体外发育及成熟提供有益的探索。

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