Spatiotemporal mapping of osteomyelitis pathogenesis guides the design of functionally graded bone regeneration scaffolds

Recurrent osteomyelitis remains a formidable challenge, with failure rates exceeding 25%. This study establishes a reproducible rabbit femoral model to systematically map the spatiotemporal pathogenesis of Staphylococcus aureus-induced osteomyelitis. Through longitudinal micro-CT and histo-morphometric analysis, we delineated a progressive pathological continuum: Acute trabecular destruction at 2 weeks advanced to subacute cortical devascularization by 4 weeks, culminating in chronic epiphyseal compromise with articular surface collapse at 6 weeks. A critical finding was the region-specific vulnerability to infection, with the diaphysis and condyle exhibiting distinct patterns of destruction. These quantitative pathoanatomical data directly inform a novel design paradigm for future bone regeneration strategies. We propose that effective therapeutic scaffolds must adopt a functionally graded approach, addressing the unique mechanical and biological requirements of each compromised region - specifically, tailored porosity gradients and architectural features for the diaphysis versus the condyle - rather than employing a uniform design. This work converts descriptive pathological progression into a set of predictive engineering criteria, providing a foundational platform for the future development of targeted infected-bone reconstruction.