Programmable Antimicrobial Nanostructured Surfaces: Opportunities and Hurdles for Clinical Translation.

Surfaces with programmable nanostructures represent a promising antimicrobial strategy that eradicates bacterial pathogens through physical membrane disruption and/or mechanically induced oxidative stress, independently of conventional antimicrobial resistance mechanisms. Despite their demonstrated and often potent in vitro efficacy, the successful clinical translation of this nanotechnology remains limited. Here, we synthesize the current understanding of how nanoscale geometry, bacterial biomechanics, and host-associated environmental factors collectively govern the antimicrobial performance of programmable nanostructured surfaces. We identify the key bottlenecks hindering clinical translation, including fabrication complexity, limited scalability, the mechanical instability of programmable nanostructured surfaces, biofouling, and reduced efficacy under physiological conditions. Emerging solutions, including flexible polymeric materials and multifunctional nanostructured surfaces, are highlighted as promising strategies to overcome these challenges and facilitate clinical translation. Ultimately, translating programmable nanostructured surfaces from laboratory proof-of-concept systems to clinically relevant applications will require coordinated advances in nanofabrication, materials engineering, mechanobiological understanding, and scalable manufacturing.