Research AppraisalSystematic Review

Multidimensional additive manufacturing micro/nanorobots: from elaborate design to smart cargo delivery

Nanoscale horizonsZhang, Yuxuan, Zeng, Guokai, Qin, Fang et al.7 July 2026DOI

Clinical Snapshot

10CEBM
Evidence: InsufficientSystematic Review

PICO Framework

P — PopulationNot applicable in the traditional clinical sense; the review addresses micro/nanorobots fabricated via multidimensional additive manufacturing (MAM) technologies intended for biomedical applications in humans
I — InterventionMultidimensional additive manufacturing (MAM) technologies — encompassing 3D, 4D, 5D, and 6D printing — for the design and fabrication of micro/nanorobots
C — ComparatorTraditional (non-additive) manufacturing methods for micro/nanorobot fabrication
O — OutcomesStructural complexity, multifunctionality, design flexibility, fabrication efficiency, and biomedical application performance (targeted drug delivery, lesion exploration, minimally invasive surgery); clinical translation potential

Bottom Line

This paper is a narrative review — not a systematic review or meta-analysis — examining multidimensional additive manufacturing (MAM) technologies for the fabrication of micro/nanorobots intended for biomedical applications. Despite its publication under a 'Review' label, it lacks the methodological hallmarks of a rigorous systematic review: there is no documented search strategy, no pre-specified inclusion criteria, no risk of bias assessment, no quantitative synthesis, and no GRADE evaluation of evidence certainty. The CEBM score of 10/100 reflects these fundamental gaps. The underlying science is genuinely interesting — 3D, 4D, 5D, and 6D printing offer conceptually compelling approaches to fabricating responsive, multifunctional micro/nanorobots — but the entire evidence base is preclinical. No human clinical data are presented or synthesised. For senior clinicians, this paper is best understood as a horizon-scanning technology overview rather than actionable clinical evidence. It has no current implications for practice change, prescribing, or patient management. Clinicians and researchers interested in this field should await first-in-human studies and regulatory engagement before considering any translational applications.

Evidence: Insufficient

Key Findings

  • Effect Size: Not applicable — no quantitative synthesis performed; no pooled effect size reported

  • Primary Outcome: Narrative synthesis of MAM technologies (3D, 4D, 5D, 6D printing) for micro/nanorobot fabrication and their reported biomedical applications including targeted drug delivery, lesion exploration, and minimally invasive surgery

  • Nnt Or Sensitivity: Not applicable — no clinical outcome data, NNT, diagnostic accuracy, or hazard ratios are reported; the review is a technology-focused narrative synthesis

  • Confidence Interval: Not applicable — no statistical analysis conducted

Clinical Application

Clinical feasibility is not established. Key barriers include: biocompatibility and long-term toxicity of fabrication materials, scalable and sterile manufacturing, in vivo actuation and navigation in complex biological environments, immune response and clearance, and regulatory approval pathways. The review acknowledges these challenges but does not provide a roadmap or timeline for resolution. No MAM-fabricated micro/nanorobots are currently approved by the Therapeutic Goods Administration (TGA) or listed on the Pharmaceutical Benefits Scheme (PBS). This technology is not referenced in current RACGP clinical guidelines for any indication. Australian researchers and clinicians should monitor this space through the TGA's Emerging Technologies program and relevant NHMRC-funded nanotechnology research initiatives. Any future clinical translation in Australia would require TGA regulatory approval as a therapeutic device or drug-device combination product, with full preclinical and clinical trial data packages. At present, this review has no direct implications for Australian clinical practice. No current clinical population. The technology is preclinical. Future potential applications may include patients requiring targeted intravascular drug delivery, oncology (tumour-targeted therapy), or minimally invasive surgical intervention — but none of these indications have been validated in human trials.

Abstract

Micro/nanorobots have attracted much attention because of their potential to perform complex tasks with high precision under controlled actuation within the human body, such as targeted cargo delivery, lesion exploration, and minimally invasive surgery. Among the various emerging fabrication technologies, multidimensional additive manufacturing (MAM) technology can enable the design and fabrication of complex structures with multifunctional characteristics. Compared with traditional manufacturing methods, MAM significantly reduces production complexity and time while enhancing design flexibility and customization. This review provides a comprehensive overview of MAM technologies for constructing micro/nanorobots, along with their applications and associated challenges in the biomedical field. In addition, emerging MAM approaches, including 4D, 5D, and 6D printing assisted by physical intelligence, machine learning, and artificial intelligence show great potential for designing and fabricating more sophisticated and intelligent micro/nanorobots, thereby advancing their clinical translation in the near future.

References

  1. 1.Zhang, Y., Zeng, G., Qin, F., Wu, B., Liang, J., Zeng, G., Tang, Y., Xu, C., Gui, C., Xiang, J., Yao, S., He, Q., Tu, Y., & Liu, K. (2026). Multidimensional additive manufacturing micro/nanorobots: from elaborate design to smart cargo delivery. Nanoscale Horizons. https://doi.org/10.1039/d5nh00795j
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