Injectable photocurable Janus hydrogel delivering hiPSC cardiomyocyte-derived exosome for post-heart surgery adhesion reduction

被引：24

作者：

Wang, Ling ^{[1
,2
]}

Chen, Peier ^{[3
,4
]}

Pan, Yuxuan ^{[3
]}

Wang, Zihan ^{[2
,5
]}

Xu, Jie ^{[1
]}

Wu, Xiaoqi ^{[6
]}

Yang, Qiao ^{[1
]}

Long, Meng ^{[2
]}

Liu, Sitian ^{[2
]}

Huang, Wenhua ^{[2
]}

Ou, Caiwen ^{[3
]}

Wu, Yaobin ^{[2
]}

机构：

[1] Southern Med Univ, Sch Biomed Engn, Biomat Res Ctr, Guangzhou 510515, Peoples R China

[2] Southern Med Univ, Sch Basic Med Sci, Dept Human Anat,Guangdong Prov Key Lab Digital Me, Guangdong Engn Res Ctr Translat Med 3D Printing A, Guangzhou 510515, Peoples R China

[3] Southern Med Univ, Affiliated Dongguan Hosp, Dongguan Peoples Hosp, Dongguan 523058, Peoples R China

[4] Southern Med Univ, Zhujiang Hosp, Dept Cardiol, Lab Heart Ctr,Heart Ctr, Guangzhou 510280, Peoples R China

[5] Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Peoples R China

[6] Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Urol & Androl, Shanghai 200001, Peoples R China

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 31期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

OXIDATIVE STRESS; FIBROBLASTS; TISSUE; DAMAGE; RISK;

D O I：

10.1126/sciadv.adh1753

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Postsurgical pericardial adhesions pose increased risks of sequelae, prolonged reoperation time, and reduced visibility in the surgical field. Here, we introduce an injectable Janus hydrogel, which exhibits asymmetric adhesiveness properties after photocrosslinking, sustained delivering induced pluripotent stem cell-derived cardiomyocyte exosomes (iCM-EXOs) for post-heart surgery adhesion reduction. Our findings reveal that iCM-EXOs effectively attenuate oxidative stress in hydrogen peroxide-treated primary cardiomyocytes by inhibiting the activation of the transcription factor nuclear factor erythroid 2-related factor 2. Notably, in rat cardiac postsurgery models, the Janus hydrogels loaded with iCM-EXOs demonstrate dual functionality, acting as antioxidants and antipericardial adhesion agents. These hydrogels effectively protect iCM-EXOs from GATA(6+) cavity macrophage clearance by inhibiting the recruitment of macrophages from the thoracic cavity. These results highlight the promising potential of iCM-EXO-laden Janus hydrogels for clinical safety and efficacy validation in trials involving heart surgery patients, with the ultimate goal of routine administration during open-heart surgeries.

引用

页数：18