"Biomimetic" approaches for heterogeneous growth of inorganic coatings have become particularly widespread in biomedical applications, where calcium phosphate (CaP) mineral coatings are used to improve biomedical implants. Changes in coating properties can influence the effects of mineral coatings on adjacent cells, but to date it has not been practical to systematically vary inorganic coating properties to optimize specific cell behaviors. Here, we present an approach to grow CaP mineral coatings in an enhanced throughput format to identify unprecedented capabilities in non-viral gene delivery. Subtle changes in coating properties resulted in widely variable transfection, and optimized coatings led to greater than 10-fold increases in transgene expression by multiple target cell types when compared to standard techniques. The enhanced transfection observed here is substrate-mediated, and related to the characteristics of the local environment near the surface of dissolving mineral coatings. These findings may be particularly translatable to medical device applications.