Adaptive Closed-Loop Vascular Navigation: A Physical-AI Framework for State-Responsive Angiogenic Guidance and Self-Extinguishing Demand Fields

Abstract

Static scaffolds and fixed growth-factor gradients provide an initial instruction but cannot respond when a vascular sprout deviates, connects, leaks, regresses, or completes perfusion. This Version 2 proposal introduces state-responsive vascular navigation. A physical-AI controller observes angiogenic dynamics in a three-dimensional microfluidic tissue model and selects permitted updates to spatial growth-factor delivery, oxygen-demand fields, interstitial flow, matrix accessibility, and vascular-maturation support. The central innovation candidate is a self-extinguishing demand field. When successful perfusion resolves the oxygen and vascular demand of a local territory, its attraction signal is reduced. This may prevent continued stimulation of an already supplied region and redirect vascular exploration toward unresolved territories. The controller does not directly command endothelial cells. It adjusts only predefined environmental variables within laboratory-approved limits. Severe leakage, collapse, occlusion-like states, toxicity, abnormal growth, or excessive uncertainty act as noncompensatory stop conditions. The proposal compares neutral, fixed-gradient, fixed-time withdrawal, perfusion-triggered withdrawal, proportional demand extinction, closed-loop navigation, sham-feedback, and relapse-response conditions. Discovery-stage adaptation is separated from locked prospective confirmation. The primary hypothesis is that state-responsive guidance will increase persistent, perfusable, low-leakage destination connections while reducing total pro-angiogenic exposure and unstable excess branching compared with fixed or open-loop controls. This is an open, falsifiable, and unvalidated preclinical research hypothesis. It is not a clinical treatment, medical advice, surgical or manufacturing protocol, proof of safety or efficacy, world-first claim, or patentability claim.