Spermbots and Their Applications in Assisted Reproduction: Current Progress and Future Perspectives

Abstract

Sperm quality is declining dramatically during the past decades. Male infertility has been a serious health and social problem. The sperm cell driven biohybrid nanorobot opens a new era for automated and precise assisted reproduction. Therefore, it is urgent and necessary to conduct an updated review and perspective from the viewpoints of the researchers and clinicians in the field of reproductive medicine. In the present review, we first update the current classification, design, control and applications of various spermbots. Then, by a comprehensive summary of the functional features of sperm cells, the journey of sperms to the oocyte, and sperm-related dysfunctions, we provide a systematic guidance to further improve the design of spermbots. Focusing on the translation of spermbots into clinical practice, we point out that the main challenges are biocompatibility, effectiveness, and ethical issues. Considering the special requirements of assisted reproduction, we also propose the three laws for the clinical usage of spermbots: good genetics, gentle operation and no contamination. Finally, a three-step roadmap is proposed to achieve the goal of clinical translation. We believe that spermbot-based treatments can be validated and approved for in vitro clinical usage in the near future. However, multi-center and multi-disciplinary collaborations are needed to further promote the translation of spermbots into in vivo clinical applications.

Keywords: assisted reproduction; biohybrid nanorobot; clinical translation; male infertility; spermbot.

Graphical abstract

Figure 1

Summary of the classification and design of spermbots. (A) The main structure of mature sperm cell. (B) The structural design of sperm cell based spermbots. (C) The structural design of sperm-like nanorobots. Note that the cyborg sperm based on piezoelectric system is still in the conceptual design stage. (D) Summary of the current designed applications of spermbots.

Figure 2

The control and functional design of spermbots. (A) The controlling methods for the sperm and nano component parts of spermbots. (B) The functional features of sperm cells. The red star labels indicate potential new considerations of sperm features for designing spermbots in the future.

Figure 3

Fertilization related journey, conditions and the corresponding solutions of spermbots. The journey of sperm cells from production to fertilization includes five main processes: spermatogenesis for sperm production, sperm maturation to obtain basic motility, semen ejaculation, sperm travel in the female genital tract, and the final fertilization at the isthmus of fallopian tube. Correspondingly, the related conditions, diseases and spermbots based solutions are also listed at the bottom of the schematic diagram. The red star labels indicate potential new directions for the applications of spermbots.

Figure 4

The challenges, laws and roadmap for translating spermbots into clinical practice (A) The current stage and next steps for the translating of spermbots into clinical practice. (B) Comparison of the traditional ARTs and the spermbots based solutions for assisted reproduction. (C) The main classes of challenges, the three laws and the roadmap for clinical translation of spermbots.