Intrauterine adhesions (IUAs) are common sequelae of cervical mucosa damage caused by uterine curettage. Establishing an anti-adhesion barrier between the damaged endometrium with a sustained-release drug capability and hence promoting endogenous regeneration of the endometrium is an available treatment for IUA. However, current therapy lacks long-term intracavitary residence, drug-delivery permeability, and tissue anti-adhesion to the endometrium. Here, we report the design of a Janus microneedle patch consisting of two layers: an adhesive inner layer with an exosomes-loaded microneedle, which endows the patch with a tissue adhesive capability as well as transdermal drug-delivery capability; and an anti-adhesion outer layer, which prevents the intrauterine membrane from postoperative adhesion. This Janus adhesive microneedle patch firmly adhered to uterine tissue, and sustainedly released ∼80% of the total loaded exosomes in 7 days, hence promoting the expression of vascular- and endothelial-related cell signals. Furthermore, the anti-adhesive layer of the microneedle patch exhibited low cell and protein adhesion performance. In rats, the microneedle patch successfully prevented uterine adhesions, improved endometrial angiogenesis, proliferation, and hormone response levels. This study provides a stable anti-adhesion barrier as well as efficient drug-release capability treatment for intrauterine adhesion treatment.

中文翻译：

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载有外泌体的 Janus 粘性微针贴片用于宫腔粘连治疗

宫腔粘连（IUAs）是刮宫术引起的宫颈粘膜损伤的常见后遗症。在受损子宫内膜之间建立具有缓释药物能力的抗粘连屏障，从而促进子宫内膜的内源性再生是IUA的一种可行治疗方法。然而，目前的治疗缺乏长期的腔内滞留、药物输送渗透性和组织对子宫内膜的抗粘连。在这里，我们报告了 Janus 微针贴片的设计，该贴片由两层组成：具有负载外泌体的微针的粘合内层，赋予贴片组织粘合能力以及透皮药物递送能力；防粘连外层，防止宫内膜术后粘连。这种Janus粘性微针贴片牢固地粘附在子宫组织上，并在7天内持续释放总负载量的约80%的外泌体，从而促进血管和内皮相关细胞信号的表达。此外，微针贴片的抗粘附层表现出较低的细胞和蛋白质粘附性能。在大鼠中，微针贴片成功预防了子宫粘连，改善了子宫内膜血管生成、增殖和激素反应水平。该研究为宫腔粘连治疗提供了稳定的抗粘连屏障以及高效的药物释放能力治疗。