AbstractBioglass 45S5 is the most widely used bioactive glass composition in orthopedics to regenerate bone tissue. Although its reactions in vitro and in vivo are well established, the impact of the local environment on the dissolution behavior in the dynamic environment is not fully understood. Here, we show that the ion concentrations released from 45S5 into Tris‐buffer solution and simulated body fluid (SBF) in a cascade system of three reactors in a series significantly differed depending on the ion concentrations in the inflow solutions to each reactor. The ion concentrations and pH of the solutions were measured after each reactor for up to 7 days. Also, the reaction layers at the glass particles were analyzed. The release of Si species into Tris decreased in the consecutive reactors from 92% to 26% and 24% at 168 h. Correspondingly, the release of Si species into SBF decreased from 35% to 20% and 19%. The share of elements in the remaining glass particles markedly varied between the reactors throughout the dissolution. The results imply that gradients of local ion concentrations have an essential effect on the dissolution of 45S5. The results provide guidelines for utilizing Bioglass 45S5 in different bone and soft tissue applications.