Dual function of poly(acrylic acid) on controlling amorphous mediated hydroxyapatite crystallization

Hydroxyapatite (HAP, Ca5(PO4)3OH), as the main inorganic component of bone, is regulated by noncollagenous proteins (NCPs) that are rich in acidic amino acid. Poly(acrylic acid) (pAA) is widely used as an NCPs mimic because of its rich in carboxyl acid groups. Here we show that pAA plays a dual role in amorphous calcium phosphate (ACP, Ca3(PO4)2) mediated HAP crystallization, in which ACP is usually considered as the precursor phase of HAP crystallization in vitro and in vivo. The appropriate concentration of pAA can promote HAP crystallization due to it is mainly incorporated into ACP and more likely leads to form smaller ACP nanoparticles, thus provide a large specific surface area to HAP nucleation. While excessive pAA (incorporated into and adsorbed on the ACP) impairs the crystallization of HAP, in that surface associated pAA prevent the nucleation of HAP on ACP. Interestingly, pAA adsorbed on the ACP surface inhibits HAP nucleation significantly and changes the aggregation events of ACP. This finding points out that appropriate regulation of pAA concentration is vital for amorphous mediated biomineralization. Moreover, this study is of considerable importance for the future regulation and design of bone substitutes associated with NCPs.