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Photoacoustic image-guided corpus cavernosum intratunical injection of adipose stem cell-derived exosomes loaded polydopamine thermosensitive hydrogel for erectile dysfunction treatment
Bioactive Materials ( IF 18.0 ) Pub Date : 2021-08-09 , DOI: 10.1016/j.bioactmat.2021.07.024
Li Liang 1 , Yi Shen 2 , Zhifeng Dong 3 , Xin Gu 4
Affiliation  

Stem cell-derived exosomes (SC-EXO) was an emerging therapeutic agent in regenerative medicine. Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction (ED) treatment. However, high vascularization of cavernous body makes effective retention a major challenge for SC-EXO intratunical injection. In this study, a Polydopamine nanoparticles (PDNPs) incorporated poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PDNPs-PELA) thermosensitive hydrogels were fabricated by a facile in situ polymerization for intratunical administration of adipose stem cell-derived exosomes (EXO). The hydrogels exhibited sol-gel transition at body temperature. Moreover, the in-situ polymerization of PDNPs using poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PELA) block copolymer as a template was found to be more stable dispersion in the gel system. After being encapsulated into the hydrogel, EXO shows sustained release behavior within two weeks. In vivo animal experiments revealed that exosomes released from hydrogel lead to the healing of endothelial cells and neurons, increase of the cavity's pressure, thereby restoring the erectile function. In particular, since the PDNPs in thermosensitive gels have excellent photoacoustic performance, the hydrogel can be accurately delivered into the tunica albuginea by the guidance of real-time photoacoustic imaging. These results suggest that the as-prepared PDNPs-PELA has a promising future as an injectable exosome carrier for ED treatment.



中文翻译:

光声图像引导海绵体鞘内注射脂肪干细胞衍生的外泌体负载聚多巴胺热敏水凝胶治疗勃起功能障碍

干细胞衍生的外泌体(SC-EXO)是再生医学中的一种新兴治疗剂。鞘内注射 SC-EXO 被认为是治疗勃起功能障碍 (ED) 的一种前瞻性方法。然而,海绵体的高血管化使得有效保留成为 SC-EXO 鞘内注射的主要挑战。在这项研究中,聚多巴胺纳米粒子 (PDNPs) 掺入了聚(乙二醇)-聚(ε-己内酯-共-丙交酯)(PDNPs-PELA)热敏水凝胶,通过简单的原位聚合制备,用于脂肪干细胞的膜内给药-衍生外泌体(EXO)。水凝胶在体温下表现出溶胶-凝胶转变。而且,发现使用聚(乙二醇)-聚(ε-己内酯-共-丙交酯)(PELA)嵌段共聚物作为模板的 PDNPs 原位聚合在凝胶系统中更稳定地分散。EXO被包裹在水凝胶中后,在两周内表现出缓释行为。体内动物实验表明,水凝胶释放的外泌体导致内皮细胞和神经元愈合,增加腔内压力,从而恢复勃起功能。特别是,由于热敏凝胶中的 PDNPs 具有优异的光声性能,在实时光声成像的引导下,水凝胶可以准确地输送到白膜中。这些结果表明,所制备的 PDNPs-PELA 作为用于 ED 治疗的可注射外泌体载体具有广阔的前景。

更新日期:2021-08-09
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