Restoring normal function and appearance after massive facial injuries with bone loss is an important unsolved problem in surgery. An important limitation of the current methods is heuristic ad hoc design of bone replacements by the operating surgeon at the time of surgery. This problem might be addressed by incorporating a computational method known as topological optimization into routine surgical planning. We tested the feasibility of using a multiresolution three-dimensional topological optimization to design replacements for massive midface injuries with bone loss. The final solution to meet functional requirements may be shaped differently than the natural human bone but be optimized for functional needs sufficient to support full restoration using a combination of soft tissue repair and synthetic prosthetics. Topological optimization for designing facial bone tissue replacements might improve current clinical methods and provide essential enabling technology to translate generic bone tissue engineering methods into specific solutions for individual patients.