Substitution of inorganic ions into β-tricalcium phosphate (β-TCP) is a well-known approach for facilitating biological functions of bioceramics. However, the dissolution mechanism of those β-TCPs is still under intensive debates. In the present study, the effect of copper substitution into β-TCP crystal structure on the local chemical structure and dissolution property of the copper-doped β-TCP (CuTCP) was investigated to clarify the dissolution mechanism of β-TCP. A copper-dependent decrease in the dissolution rate of CuTCP with time was observed. The 1H → 31P nuclear magnetic resonance (NMR) spectra of 10 mol% copper-doped β-TCP after the dissolution test demonstrated an amorphous hydrated layer on the surface of β-TCP core particles, which contained hydroxyapatite and dicalcium phosphate dihydrate and anhydrate. As such, all the dissolution curves could be curve-fitted by a heterogeneous dissolution model composing of fast and slow dissolution components. Overall, dissolution mechanism could be proposed as follows: the CuTCP particles initially dissolved by hydrolysis based on the fast dissolution component. Subsequently, the amorphous hydrated layers were formed on their surface, and caused the diffusion-controlled dissolution. As the result, the slow dissolution component would be dominant, and led to the decreased dissolution rate. Understanding the dissolution mechanism of copper doped β-tricalcium phosphate (CuTCP) is crucial for designing an angiogenetic controlled copper release CuTCP for therapeutic biomaterials. However, dissolution mechanism of β-TCP or CuTCP is still under intensive debates. This study demonstrated for the first time, that amorphous hydrated layers were formed on the CuTCP particle surface during its dissolution process, which caused a diffusion-controlled dissolution, and decreased the dissolution rate of CuTCP. This work not only provided a novel dissolution mechanism of β-TCP or CuTCP, but also a new finding for designing an angiogenetic controlled copper release CuTCP for therapeutic biomaterials. [ABSTRACT FROM AUTHOR]