Document Type : Review Article
Authors
1
Department of Biology, Faculty of Engineering and Basic Sciences, University of Science and Arts, Yazd, Iran.
2
Medical Nanotechnology Department, School of Advanced Medical Technologies, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
3
Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
4
Tissue Engineering and Applied Cell Sciences Department, School of Advanced Medical Technologies, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
10.22034/jrb.2026.07.V2I1A3
Abstract
Premature Ovarian Insufficiency (POI), is a clinically significant reproductive endocrine disorder defined by the cessation of ovarian function prior to age 40, with a global prevalence of approximately 1–2% among women of reproductive age. The condition manifests as a constellation of reproductive and systemic sequelae, including infertility, hypoestrogenism, accelerated bone loss, heightened cardiovascular risk, and considerable psychosocial burden. While current standard of care predominantly centers on hormone replacement therapy, which merely compensates for hormonal deficiency without addressing the underlying pathological process of follicular depletion, nanoengineered exosome platforms have emerged as a paradigm-shifting therapeutic opportunity for restoring functional ovarian capacity. This comprehensive review synthesizes advances published between 2022 and 2026 in the evolving landscape of nanoengineered exosome-based interventions for POI. Exosomes represent superior alternatives to intact mesenchymal stem cells due to their inherent biocompatibility, low immunogenicity, ability to traverse biological barriers, and greater potential for standardization. Recent developments in advanced cargo loading technologies (CRISPR-Cas9-mediated genetic engineering of parent MSCs, and sonication-mediated encapsulation of small-molecule therapeutics), surface engineering strategies (ovarian homing peptides, AMHR2-targeting aptamers, and bio orthogonal click chemistry conjugation), and hybrid nanoplatforms (exosome-liposome hybrids, ROS-responsive polymer coatings, and injectable thermosensitive hydrogel composites) are critically evaluated. The evidence base has substantially advanced both mechanistic understanding and engineering capabilities, with CRISPR-guided cargo enrichment, aptamer-based ovarian targeting, and stimuli-responsive polymer-exosome hybrids representing standout developments. As these technologies mature, nanoengineered exosomes stand as one of the most promising vehicles for achieving genuine ovarian regeneration in POI transitioning from theoretical aspiration toward clinical reality.
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