The topology optimization (TO) of structures to be produced using additive manufacturing (AM) is explored using a data-driven constraint function that predicts the minimum producible size of small features in different shapes and orientations. This shape- and orientation-dependent manufacturing constraint, derived from experimental data, is implemented within a TO framework using a modified version of the moving morphable components (MMC) approach. Because the analytic constraint function is fully differentiable, gradient-based optimization can be used. The MMC approach is extended in this work to include a “bootstrapping” step, which provides initial component layouts to the MMC algorithm based on intermediate solid isotropic material with penalization (SIMP) topology optimization results. This “bootstrapping” approach improves convergence compared with reference MMC implementations. Results from two compliance design optimization example problems demonstrate the successful integration of the manufacturability constraint in the MMC approach, and the optimal designs produced show minor changes in topology and shape compared to designs produced using fixed-radius filters in the traditional SIMP approach. The use of this data-driven manufacturability constraint makes it possible to take better advantage of the achievable complexity in additive manufacturing processes, while resulting in typical penalties to the design objective function of around only 2% when compared with the unconstrained case.