In situ mechanostimulation of biohybrid millirobots for enhanced cell functionality and delivery

This study proposes a perforated, soft millirobot with dual functions: in situ mechanostimulation to enhance cell functionality and local cell delivery. Following protein modification and silica coating, the soft millirobots exhibit excellent biocompatibility, promoting cell adhesion and tissue ingrowth within their perforated architectures under both in vitro and in vivo conditions. They can apply in situ mechanostimulation to various cellular morphologies, including two-dimensional (2D) cell sheets, 3D cell-laden hydrogels, and ex vivo tissue models. The mechanical stimulation improves the functionality of muscle cells by enhancing cellular orientation, myotube contraction, and myocyte differentiation. In parallel, we develop an integrated robotic platform combining magnetic actuation with ultrasound imaging. It demonstrates the proof of principle that delivers 2D cell-sheet and 3D cell-laden biohybrid millirobots to narrow regions in an ex vivo pig liver model. This work expands the potential applications of soft millirobots in mechanobiology studies and future cell-based therapies.