Programmable immune biointerfaces for cell-state control through mechanotransduction, stimuli-responsive design, and AI-guided modeling in regeneration and cancer

Biomaterials are increasingly recognized as active immune-regulatory interfaces rather than passive structures tolerated by tissues. This Review develops the concept of programmable immune biointerfaces as material systems that organize immune-state behavior through coordinated mechanical, biochemical, structural, degradative, and stimulus-responsive cues. Mechanotransduction is presented as a central interface-to-cell signaling axis through which material properties are converted into immune-regulatory programs involving inflammatory activation, stromal remodeling, antigen presentation, fibrosis, suppression, and tissue integration. Stimuli-responsive materials extend this logic by enabling external or tissue-derived triggers to regulate when, where, and how immune-active signals are exposed, released, remodeled, or withdrawn. Regeneration and cancer illustrate divergent but related settings for engineered immune control: regenerative interfaces aim to support resolution, vascularization, matrix remodeling, and tissue integration, whereas cancer-associated interfaces model or redirect mechanically constrained, antigenically structured, and immunologically suppressive immune states. Finally, predictive programmable biocompatibility is framed as a design approach that links material variables, biological interface responses, immune-state outputs, AI-guided modeling, and closed-loop refinement. This framework shifts biocompatibility from tissue tolerance toward controllable immune-state trajectory design.