A multiscale pathoanatomical atlas guides the design of functionally graded, anatomically intelligent implants for chronic osteomyelitis.

Abstract

Chronic osteomyelitis remains a formidable clinical challenge because conventional biomaterials, which are designed for spatially uniform defects, cannot match the hierarchical, compartmentalized progression of deep bone infection. Using a clinically relevant rabbit femoral osteomyelitis model, we construct a multiscale pathoanatomical atlas of <i>S</i>. <i>aureus</i> infection, revealing a coherent disease cascade: medullary colonization, invasion of the immunoprivileged osteocyte lacuno-canalicular system (OLCS), region-specific bone destruction, and ultimate formation of a biomechanically incompetent sequestrum. Guided explicitly by this anatomical blueprint, we design and computationally optimize a dual-component bioactive material system that mirrors and counteracts the infection hierarchy. This dual-component implant integrates a 3D-printed, load-bearing macro-scaffold for mechanical stabilization and bone regeneration with infiltrative microspheres capable of penetrating trabecular microdomains and releasing antimicrobials within the marrow and cortical compartments, directly targeting bacterial reservoirs. <i>In vivo</i> validation demonstrates that this system enables simultaneous eradication of deep-seated infection, resolution of chronic inflammation, and restoration of structurally competent bone. Collectively, this work establishes imaging-resolved anatomical mapping as a generative framework for bioactive material design and provides a strategy that may be adapted for developing spatially adaptive therapeutic systems against complex tissue infections.