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. 2024 Sep;36(39):e2407750.
doi: 10.1002/adma.202407750. Epub 2024 Aug 8.

A Dopamine-Modified Hyaluronic Acid-Based Mucus Carrying Phytoestrogen and Urinary Exosome for Thin Endometrium Repair

Chenchen Li  1 , Xiyang Tan  2 , Dashi Deng  1 , Chenfan Kong  2 , Lida Feng  3 , Weijing Wang  4 , Kaida Lin  4 , Yuqing Li  5 , Qifang Lei  5 , Lisha Liu  1 , Tao Tao  1 , Ruile Pan  6 , Guangzhi Li  1 , Song Wu  1   5
Affiliations

A Dopamine-Modified Hyaluronic Acid-Based Mucus Carrying Phytoestrogen and Urinary Exosome for Thin Endometrium Repair

Chenchen Li et al. Adv Mater. 2024 Sep.

Abstract

Thin endometrium (TE) is closely associated with infertility in reproductive medicine. Estrogen therapy gains unsatisfactory outcomes. In this study, an artificial mucus based on dopamine (L-DOPA)-modified hyaluronic acid combining phytoestrogen cajaninstilbene acid and rat urinary exosomes (CUEHD) is constructed for TE treatment using a rat TE model. In the rat TE model, the dominant elastic behavior and adhesive properties of CUEHD guarantee adequate retention, rendering superior synergistic treatment efficacy and favorable biosafety characteristics. CUEHD treatment significantly increases endometrial thickness and promotes receptivity and fertility. Mechanistically, estrogen homeostasis, inflammation inhibition, and endometrial regeneration are achieved through the crosstalk between ER-NLRP3-IL1β and Wnt-β catenin-TGFβ-smad signaling pathways. Moreover, the therapeutic potential of exosomes from human urine and adipose tissue-derived stem cells (ADSCs) and rat ADSCs are also demonstrated, indicating extensive use of the artificial mucus system. Thus, this study illustrates a platform combining phytoestrogen and exosomes with promising implications for TE treatment.

Keywords: artificial mucus; phytoestrogen; thin endometrium; urinary exosome.

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