BioNICs: Biomaterial-enabled neural interfaces with closed-loop control for brain disorders

Biomaterial-enabled neural interfaces with closed-loop control (BioNICs) integrate neural sensing, state estimation, and responsive intervention within one therapeutic framework. Material composition and architecture influence tissue coupling, signal transduction, therapeutic actuation, and chronic stability. Mechanically compliant polymers and hydrogels can reduce interfacial strain; conductive and mixed ionic-electronic materials can improve electrical and electrochemical coupling; and stimulus-responsive materials can enable localized energy conversion or controlled drug release. BioNICs are therefore relevant to brain disorders requiring continuous physiological monitoring and state-dependent treatment. However, substantial translational gap remains. Clinically established closed-loop therapies rely mainly on metallic electrodes, polymer insulation, and hermetic packaging, whereas conductive polymers, nanocomposites, hydrogels, microbubbles, biohybrid interfaces, and integrated drug-delivery systems have been evaluated chiefly in vitro , in rodents, or over short implantation periods. Greater complexity in materials and functionality does not necessarily enhance therapeutic performance and may, in fact, give rise to delamination, electrochemical degradation, stimulation artifacts, calibration drift, and packaging failure, as well as additional safety risks. This review examines BioNIC architecture, including sensing, intervention, control algorithms, biomaterials, and system integration, and illustrates applications in episodic network disorders, psychiatric conditions, neurodegenerative diseases, and structural brain injury. We focus on trade-offs in combining high-fidelity electrophysiological recording, neurochemical and physical sensing, localized electrical, optical, acoustic, or magnetic actuation, and microenvironment-responsive drug delivery. Ultimately, this review emphasizes that translating the intrinsic advantages of intelligent biomaterials into clinical benefit requires moving beyond isolated component innovation toward long-term system-level validation linking material performance to reliability, biological safety, algorithmic interpretability, and clinically meaningful outcomes.