Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, 48109.
Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, 48109.
J Biomed Mater Res A. 2018 May;106(5):1381-1389. doi: 10.1002/jbm.a.36338. Epub 2018 Feb 5.
A common irreversible adverse effect of life-saving anticancer treatments is loss of gonadal endocrine function and fertility, calling for a need to focus on post-treatment quality of life. Here, we investigated the use of poly(ethylene glycol)-vinyl sulfone (PEG-VS) based capsules to support syngeneic donor ovarian tissue for restoration of endocrine function in mice. We designed a dual immunoisolating capsule (PEG-Dual) by tuning the physical properties of the PEG hydrogels and combining proteolytically degradable and nondegradable layers to meet the numerous requirements for encapsulation and immunoisolation of ovarian tissue, such as nutrient diffusion and tissue expansion. Tuning the components of the PEG-Dual capsule to have similar physical properties allowed for concentric encapsulation. Upon implantation, the PEG-based capsules supported ovarian tissue survival and led to a significant decrease in follicle stimulating hormone levels 60 days postimplantation. Mice that received the implants resumed regular estrous cycle activity and follicle development in the implanted grafts. The PEG-Dual capsule provided an environment conducive for tissue survival, while providing a barrier to the host environment. This study demonstrated for the first time that immunoisolating PEG-VS capsules can support ovarian follicular development resulting in the restoration of ovarian endocrine function and can be applied to future allogeneic studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1381-1389, 2018.
救命抗癌治疗的一个常见的不可逆的不良影响是性腺内分泌功能和生育能力的丧失,这就需要关注治疗后的生活质量。在这里,我们研究了使用聚乙二醇-乙烯砜(PEG-VS)基胶囊来支持同种异体供体卵巢组织,以恢复小鼠的内分泌功能。我们通过调整 PEG 水凝胶的物理性质并结合可蛋白水解降解和不可降解层来设计双重免疫隔离胶囊(PEG-Dual),以满足卵巢组织包封和免疫隔离的众多要求,例如营养扩散和组织扩张。调整 PEG-Dual 胶囊的成分使其具有相似的物理性质,从而实现同心包封。植入后,PEG 基胶囊支持卵巢组织存活,并导致植入后 60 天卵泡刺激素水平显着降低。接受植入物的小鼠恢复了植入移植物中的正常发情周期活动和卵泡发育。PEG-Dual 胶囊提供了有利于组织存活的环境,同时为宿主环境提供了屏障。这项研究首次证明,免疫隔离 PEG-VS 胶囊可以支持卵泡发育,从而恢复卵巢内分泌功能,并可应用于未来的同种异体研究。©2018 年 Wiley 期刊,公司。生物医学材料研究部分 A:106A:1381-1389,2018 年。