Micro/nanomotors for biofilm remediation: Nanoarchitectonic breakthroughs with a focus on regulatory and clinical translation challenges

Biofilm-associated bacterial infections, notorious for their resistance to standard therapies, pose a critical challenge in clinical practice. Micro and nanomotors (MNMs) have emerged as dynamic tools capable of penetrating biofilm matrices and enabling targeted antimicrobial delivery through autonomous motion. Recent advances in nanoarchitectonic design, spanning fuel-free or chemical propulsion, biohybrid systems, and multimodal actuation, significantly enhance their therapeutic precision and biocompatibility. This review critically examines the evolution of MNM materials, geometries, and designs, emphasizing their mechanical disruption of extracellular polymeric substances and synergistic bactericidal effects. Innovations such as cascade-driven MNMs and stimuli-responsive platforms demonstrate >90 % biofilm eradication in vitro and accelerated wound healing in vivo. What distinguishes this review from existing literature is its integrated focus on regulatory and translational barriers to clinical adoption, an aspect seldom addressed in prior MNM reviews. In addition to advances in materials and design, we discuss challenges that must be overcome for clinical translation, including long-term biosafety, degradation, scalable manufacturing under Good Manufacturing Practice (GMP), and regulatory ambiguities surrounding nanoscale medical devices. We outline a path forward for addressing these barriers by emphasizing the need for standardized toxicity testing, stronger interdisciplinary collaboration, and the use of emerging regulatory tools such as Safe(r) Innovation Approaches (SIA), the EU's Safe and Sustainable by Design (SSbD) initiative, and regulatory sandboxes to help accelerate clinical translation. By integrating material and design innovation with regulatory foresight, MNM technology holds transformative potential for combating antibiotic-resistant infections and redefining the eradication of biofilms.