A Sustained Electronic Signaling Platform for Restoring Vascular Sensitivity and Systemic Homeostasis in Enzyme-Deficient Environments

Biological signaling fundamentally relies on enzymatic integrity; however, chronic disease and aging induce irreversible enzymatic "uncoupling," creating fatal metabolic bottlenecks. While recent advances in materials science have focused on overcoming physical barriers to improve drug delivery [1], a critical challenge remains: the functional failure of endogenous machinery even after successful delivery. To address this, we report a Solid-state Signaling Transducer (SST) platform, the Boron-induced Amorphous Carbon Engine (B-ACE), designed to physically bypass dysfunctional enzymatic pathways. B-ACE utilizes a functional amorphous state termed "Active Disorder," which provides a high-density, three-dimensional interface for charge transfer. Unlike rigid crystalline structures, this configuration offers a stochastic network of junctions that facilitate quantum tunneling via p-type holes (h+), effectively replacing traditional enzymatic catalysis with a direct physical relay. Electrochemical analysis identified a potential-triggered transition peaking at 0.8 V, marking the activation threshold for hole-induced signaling. Crucially, the acidic gastric environment (pH 1.5 to 2.5) functions as a "protonic primer," effectively lowering this activation energy by approximately 0.35 V through Nernstian kinetics. This synergy enables the SST to fire autonomously within the physiological potential range, transforming the gastrointestinal tract into a physical ignition site for systemic signaling. The efficacy of this "physical bypass" was validated through multi-organ studies. B-ACE demonstrated a 46-fold enhancement in non-enzymatic NO generation in eNOS-/- models, effectively substituting for missing enzymatic functions. In spontaneously hypertensive rat (SHR) models, it achieved a superior vasorelaxation potency of pD2 approx. 7.95 with sustained signaling exceeding 18 hours. Furthermore, the platform restored neural and intestinal homeostasis by protecting dopaminergic neurons and suppressing inflammatory factors (NLRP3), showcasing its potential as a "universal recalibrator." This marks a paradigm shift from delivery-centric pharmacology to a bypass-centric bio-electronic intervention for systemic homeostatic recovery.