Biomimetic inorganic-organic hybrid nanoparticles from magnesium-substituted amorphous calcium phosphate clusters and polyacrylic acid molecules

Abstract

Amorphous calcium phosphate (ACP) has been widely found during bone and tooth biomineralization, but the meta-stability and labile nature limit further biomedical applications. The present study found that the chelation of polyacrylic acid (PAA) molecules with Ca 2+ ions in Mg-ACP clusters (~2.1 ± 0.5 nm) using a biomineralization strategy produced inorganic-organic Mg-ACP/PAA hybrid nanoparticles with better thermal stability. Mg-ACP/PAA hybrid nanoparticles (~24.0 ± 4.8 nm) were pH-responsive and could be efficiently digested under weak acidic conditions (pH 5.0–5.5). The internalization of assembled Mg-ACP/PAA nanoparticles by MC3T3-E1 cells occurred through endocytosis, indicated by laser scanning confocal microscopy and cryo-soft X-ray tomography. Our results showed that cellular lipid membranes remained intact without pore formation after Mg-ACP/PAA particle penetration. The assembled Mg-ACP/PAA particles could be digested in cell lysosomes within 24 h under weak acidic conditions, thereby indicating the potential to efficiently deliver encapsulated functional molecules. Both the in vitro and in vivo results preliminarily demonstrated good biosafety of the inorganic-organic Mg-ACP/PAA hybrid nanoparticles, which may have potential for biomedical applications.

Advanced materials for enamel remineralization

“…The HPO and -COO- can work together to attract Ca 2+ and form stable Ca 2+ triangles, which can develop into the nucleation core of ACP ( Zeng et al, 2021 ). PAA can also chelate with Ca 2+ while maintaining liquid phase stability and transporting ions continuously for subsequent biomineralization ( Chen R. et al, 2020 ; Xu et al, 2020 ; Li N. et al, 2021 ). Furthermore, PAA can direct the transformation of ACP to form acicular microcrystals ( Wang et al, 2018 ).…”

Biodegradable magnesium phosphates in biomedical applications

“…The AMCP/PAA hybrid NPs exhibited good stability and pH-responsive dissolution characteristics, which could be efficiently digested under weak acidic conditions (pH 5.0–5.5). 19 The above examples indicate that the crystallization process of MCPs can be well controlled by adding biomolecules or organic additives, which provides guidance for the preparation of stable AMCP.…”

“…16 As most of the Mg in the human body is stored in bone, various Mg-doped calcium phosphate (CaP) biominerals have been widely developed for biomedical applications. [17][18][19][20][21] In addition, a Mg 2+ ion has a vital influence on the crystallization of CaP biominerals, and it can regulate the phase and structure of CaPs, [22][23][24] which provides a simple strategy for the design and synthesis of bionic CaP minerals.…”

3D biocompatible bone engineering foams with tunable mechanical properties and porous structures

“…29,30 Amorphous calcium phosphate is widely found in bones and readily transports calcium and phosphorus ions, promoting bone development. [31][32][33] Citrate promotes the stabilization of amorphous calcium phosphate, and calcium ions are able to induce osteoblast precursor differentiation via growth factor signaling pathways or support bone tissue growth by stimulating additional processes. 34,35 In this study, amorphous calcium phosphate/calcium citrate composite powders (CAP) were prepared by using a co-precipitation method.…”

“…To address this limitation, the mechanical properties are often enhanced by changing the ratio of reactants or adding inorganic fillers 29,30 . Amorphous calcium phosphate is widely found in bones and readily transports calcium and phosphorus ions, promoting bone development 31–33 . Citrate promotes the stabilization of amorphous calcium phosphate, and calcium ions are able to induce osteoblast precursor differentiation via growth factor signaling pathways or support bone tissue growth by stimulating additional processes 34,35 …”