Liang Li, Shen Yi, Dong Zhifeng, Gu Xin
Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
Bioact Mater. 2021 Aug 9;9:147-156. doi: 10.1016/j.bioactmat.2021.07.024. eCollection 2022 Mar.
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.
干细胞衍生的外泌体（SC-EXO）是再生医学中一种新兴的治疗剂。海绵体内注射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海绵体内注射的一项重大挑战。在本研究中，通过简便的原位聚合法制备了一种包含聚多巴胺纳米颗粒（PDNPs）的聚（乙二醇）-聚（ε-己内酯-共-丙交酯）（PDNPs-PELA）热敏水凝胶，用于脂肪干细胞衍生外泌体（EXO）的海绵体内给药。该水凝胶在体温下呈现溶胶-凝胶转变。此外，发现以聚（乙二醇）-聚（ε-己内酯-共-丙交酯）（PELA）嵌段共聚物为模板原位聚合的PDNPs在凝胶体系中具有更稳定的分散性。EXO被包裹入水凝胶后，在两周内呈现出缓释行为。体内动物实验表明，水凝胶释放的外泌体可促进内皮细胞和神经元的修复，增加海绵体压力，从而恢复勃起功能。特别是，由于热敏凝胶中的PDNPs具有出色的光声性能，该水凝胶可在实时光声成像的引导下准确地递送至白膜。这些结果表明，所制备的PDNPs-PELA作为一种用于治疗ED的可注射外泌体载体具有广阔的前景。
