Chem · Feb 16, 2026

TriCAN: A phase-transition molecular robot realizing closed-loop sense-compute-actuate control for inflammation-triggered bone regeneration

By Wei X, Ding F, Li J et al.

Programmable autonomy is central to nanorobotics, yet most molecular devices depend on enzyme cascades, gene circuits, or external fields for decision-making. We present TriCAN (tri-phasic cell-adaptive nanorobot), a single-peptide molecular robot that implements a closed-loop sense-compute-actuate cycle solely through reversible phase transitions. TriCAN contains three covalently linked domains: a mesenchymal stem cell (MSC)-homing sensor, a histidine-methionine pentamer processor that converts acidic pH and reactive-oxygen stress into gel-to-condensate-to-solution transitions, and a bone morphogenetic protein (BMP)-peptide effector that is sterically caged until the final phase. The processor executes an analog "enable" gate on MSC contact, a dual-input AND gate on acidic pH and reactive oxygen species (ROS), and a time-delay gate set by condensate dissolution kinetics. This phase-transition logic enables fully enzyme-free computation, requires no external power, and fits into a molecular footprint. In rodent models of chronic and diabetic periodontitis, TriCAN remained dormant in healthy sites yet restored osteogenesis and regenerated alveolar bone without ectopic ossification or toxicity.

doi.org/10.1016/j.chempr.2025.102906Open accessInterventions