The controlled release of cell differentiating agents is crucial in many aspects of regenerative medicine. Here we propose the use of hybrid calcite single crystals as micro-carriers for the controlled and localized release of retinoic acid, which is entrapped within the crystalline lattice. The release of retinoic acid occurs only in the proximity of stem cells, upon dissolution of the calcite hybrid crystals that are dispersed in the fibrin scaffold. These hybrid crystals provide a sustained dosage of the entrapped agent. The environment provided by this composite scaffold enables differentiation towards neuronal cells that form a three-dimensional neuronal network.