Structural effects of phosphate groups on apatite formation in a copolymer modified with Ca2+ in a simulated body fluid

Abstract

Organic–inorganic composites are novel bone substitutes that can ameliorate the mismatch of Young's moduli between natural bone and implanted ceramics. Phosphate groups contribute to the formation of apatite in a simulated body fluid (SBF) and the adhesion of osteoblast-like cells. Therefore, modification of a polymer with these functional groups is expected to enhance the ability of the organic–inorganic composite to bond with bone. Two phosphate groups have been used, phosphonic acid (–C–PO₃H₂) and phosphoric acid (–O–PO₃H₂). However, the effects of structural differences between these phosphate groups have not been clarified. In this study, the apatite formation of copolymers modified with Ca²⁺ and either –C–PO₃H₂ or –O–PO₃H₂ was examined. The mechanism of apatite formation is discussed based on analytical and computational approaches. The copolymers containing –O–PO₃H₂, but not those containing –C–PO₃H₂, formed apatite in the SBF, although both released similar amounts of Ca²⁺ into the SBF. Adsorption of HPO₄²⁻ from –O–PO₃H₂ in the SBF following Ca²⁺ adsorption was confirmed by zeta-potential measurement and X-ray photoelectron spectroscopy. The measurement of the complex formation constant revealed that the –O–PO₃²⁻⋯Ca²⁺ complex was thermodynamically unstable enough to convert into CaHPO₄, which was not the case with –C–PO₃²⁻⋯Ca²⁺. The formation of CaHPO₄-based clusters was found to be a key factor for apatite nucleation. In conclusion, this study revealed that modification with –O–PO₃H₂ was more effective for enhancing apatite formation compared with –C–PO₃H₂.