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Objective To develop and validate a machine learning (ML) approach for automatic three-dimensional (3D) histopathological grading of osteochondral samples imaged with contrast-enhanced micro-computed tomography (CEμCT). Design A total of 79 osteochondral cores from 24 total knee arthroplasty patients and two asymptomatic donors were imaged using CEμCT with phosphotungstic acid -staining. Volumes-of-interest (VOI) in surface (SZ), deep (DZ) and calcified (CZ) zones were extracted depth-wise and subjected to dimensionally reduced Local Bi