Minimally Invasive In Vivo Fabrication of Multiscale Biohybrid Systems

Multiscale biohybrid systems integrating living materials with minimally invasive in vivo fabrication offer new opportunities for precise diagnosis, physiological monitoring, and tissue regeneration. This review provides a unified perspective on their design and therapeutic integration, organizing recent advances across multiscale material design, minimally invasive fabrication, spatiotemporal co-engineering, and functional applications. Three emerging principles are identified: multiscale coupling bridges material architectures with cellular and tissue responses; spatiotemporal coordination integrates precise in vivo construction with dynamic material and biological evolution; and sensing-regeneration feedback extends biohybrid systems from passive repair toward responsive therapeutic regulation. Building on these principles, we highlight machine learning-assisted material discovery, multi-site fabrication, and intelligent feedback control as key directions for developing adaptive, closed-loop therapeutic systems. Together, these insights provide design guidance for translating minimally invasive multiscale biohybrid systems toward next-generation patient-centered healthcare.