The inability to sufficiently prevent and/or repair chemically-etched dental enamel serves as one example that underlines the importance and need for the development of innovative biomaterials for therapeutic applications. In this work we explored the seeding capability of 225 ppm and 1100 ppm fluoride with and without a novel β-tricalcium phosphate-silica-urea (TCP-Si-Ur) biomaterial (concentrations of 20, 40, 80, and 200 ppm) to mineralize into acid-etched bovine enamel. The nature of the mineralization was evaluated by measuring the fluoride and phosphate uptake into the eroded enamel, as well as the orthophosphate microstructure using infrared (IR) spectroscopy. These enamel fluoride uptake and IR experiments revealed a fluoride dose response exists for eroded enamel treated with 225 and 1100 ppm F. The inclusion of 20, 40, and 80 ppm TCP-Si-Ur with 225 ppm F was similar to 225 ppm F alone and did not produce a fluoride uptake dose response; however, 200 ppm TCP-Si-Ur combined with 1100 ppm F improved raw fluoride uptake relative to 1100 ppm F. Furthermore, we found the combination of either 225 ppm or 1100 ppm fluoride plus TCP-Si-Ur at different loading levels leads to unique and significant mineral integration into the PO4 enamel network, including the formation of P-F bonds. The observations reported herein demonstrate the combination of fluoride plus a novel TCP-Si-Ur biomaterial produces synergistic mineralization and bears significantly on eroded enamel microstructure.