National Engineering Research Centre for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China.
School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, P. R. China.
Proc Natl Acad Sci U S A. 2024 Dec 3;121(49):e2407809121. doi: 10.1073/pnas.2407809121. Epub 2024 Nov 18.
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.
勃起功能障碍（ED）是男性生育能力和生活质量的主要威胁，间充质干细胞（MSCs）是一种很有前途的治疗选择。然而，由于 MSC 在海绵体组织中的保留率和存活率低，治疗效果受到了影响。在这里，我们开发了一种由嵌入磁性纳米链的超软水凝胶微球组成的创新磁性软微机器人，用于 MSC 递送。该设计还具有苯硼酸基团，可清除活性氧（ROS）。超软微机器人的杨氏模量小于 1 kPa，可在狭窄的血管内自适应其形状，确保 MSC 在海绵体中均匀分布。我们的研究结果表明，与传统的 MSC 注射相比，MSC 递送微机器人（MSC-Rob）显著提高了 MSC 的保留率和存活率。在大鼠和比格犬 ED 模型中，MSC-Rob 治疗加速了海绵体组织的修复，并恢复了勃起功能。单细胞 RNA 测序（scRNA-seq）显示，MSC-Rob 治疗通过增加再生巨噬细胞的存在，促进了海绵体中的神经和血管再生。总的来说，我们的 MSC-Rob 不仅推进了 MSC 治疗 ED 的临床应用，而且拓宽了微机器人在其他细胞治疗中的应用范围。
