Next-generation smart ophthalmic biomaterials: From passive response to active interaction and closed-loop control.

Ophthalmic biomaterials are undergoing a rapid transition from inert implants to intelligent, adaptive systems that respond to the spatiotemporal complexity of ocular disease. Conventional materials provide structural support and baseline biocompatibility but rarely adapt to the evolving ocular microenvironment shaped by biochemical and biomechanical cues. Recent advances have delivered stimuli-responsive platforms that release therapeutics or modulate mechanics in response to stimuli such as pH, temperature, enzymatic activity, or mechanical strain. Yet most current strategies remain reactive or preprogrammed, lacking closed-loop, autonomous control. Here we present an evolutionary framework for ophthalmic biomaterials, tracing the shift from passive structures to interactive and emerging closed-loop systems that integrate sensing, on-board decision-making, and actuation. We synthesize advances across the first three generations, delineate core design principles, functional transitions, and clinical implementations, and highlight systems-level integration challenges. Finally, we identify critical opportunities and design principles for intelligent, self-adaptive platforms, providing a conceptual basis for the rational design of next-generation, closed-loop ocular therapies.