Erectile dysfunction (ED) is a major threat to male fertility and quality of life, and mesenchymal stromal cells (MSCs) are a promising therapeutic option. However, therapeutic outcomes are compromised by low MSC retention and survival rates in corpus cavernosum tissue. Here, we developed an innovative magnetic soft microrobot comprising an ultrasoft hydrogel microsphere embedded with a magnetic nanoparticle chain for MSC delivery. This design also features phenylboronic acid groups for scavenging reactive oxygen species (ROS). With a Young's modulus of less than 1 kPa, the ultrasoft microrobot adapts its shape within narrow blood vessels, ensuring a uniform distribution of MSCs within the corpus cavernosum. Our findings showed that compared with traditional MSC injections, the MSC delivery microrobot (MSC-Rob) significantly enhanced MSC retention and survival. In both rat and beagle ED models, MSC-Rob treatment accelerated the repair of corpus cavernosum tissue and restored erectile function. Single-cell RNA sequencing (scRNA-seq) revealed that MSC-Rob treatment facilitates nerve and blood vessel regeneration in the corpus cavernosum by increasing the presence of regenerative macrophages. Overall, our MSC-Rob not only advances the clinical application of MSCs for ED therapy but also broadens the scope of microrobots for other cell therapies.
Proceedings of the National Academy of Sciences of the United States of America. 2024 Nov 18 [Epub]
Shuting Wang, Zhenqing Wang, Zongshan Shen, Min Zhang, Dongdong Jin, Ke Zheng, Xuemin Liu, Muyuan Chai, Zhenxing Wang, Ani Chi, Serge Ostrovidov, Hongkai Wu, Dan Shao, Guihua Liu, Kai Wu, Kam W Leong, Xuetao Shi
National Engineering Research Centre for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China., Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, P. R. China., Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, P. R. China., Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China., School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen 518071, P. R. China., School of Materials Science and Engineering, Dongguan University of Technology, Dongguan 523808, P. R. China., Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku 113-8510, Tokyo, Japan., Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong 999077, P. R. China., Reproductive Centre The Sixth Affiliated Hospital Sun Yat-sen University, Guangzhou 510655, P. R. China.