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A novel reconstructive prosthesis was designed with topological optimization (TO) and a lattice structure to enhance biome-chanical and biological properties in the proximal tibia. The biomechanical performance was validated through finite element analysis (FEA) and biomechanical tests. The tibia with inhomogeneous material properties was reconstructed according to computed tomography images, and different components were designed to simulate the operation. Minimum compliance TO subject to a volume fraction constraint combined with a graded lattice structure was utilized to redesign the prosthesis. FEA was performed to evaluate the mechanical performances of the tibia and implants after optimization, including stress, micromotion, and strain energy. The results were analyzed by paired-samples t tests, and p<0.05 was considered significant. Biomechanical testing was used to verify the tibial stresses. Compared to the original group (OG), the TO group (TOG) exhibited lower stress on the stem, and the maximum von Mises stresses were 87.2 and 53.1 MPa, respectively, a 39.1%reduction (p<0.05). Conversely, the stress and strain energy on the tibia increased in the TOG. The maximum von Mises stress values were 16.4 MPa in the OG and 22.9 MPa in the TOG with a 39.6% increase (p <0.05), and the maximum SED value was 0.026 MPa in the OG and 0.042 MPa in the TOG, corresponding to an increase of 61.5%(p<0.05). The maximum micromotions in the distal end of the stem were 135 μm in the OG and 68 μm in the TOG, almost a 50%reduction. The stress curves of the biomechanical test coincided well with the FEA results. The TO approach can effectively reduce the whole weight of the prosthesis and improve the biomechanical environment of the tibia. It could also pave the way for next-generation applications in orthopedics surgery.