A Kinetic Model for Hydroxyapatite Precipitation in Mineralizing Solutions

Amorphous calcium phosphate (ACP) is a metastable precursor phase for bone formation, and it can transform into the thermodynamic stable mineral phase, hydroxyapatite (HAP, the main inorganic phase in bone), under physiological conditions. In a biological system, it has been documented that Mg2+ can effectively stabilize ACP to ensure a regulation of biomineralization kinetics. In this study, we investigate the effect of another alkaline earth metal ion, Sr2+, on ACP stabilization. Although Sr2+ plays an important role in bone formation, its mechanism is poorly understood. We find that Sr2+ itself has less stabilization effect on ACP in comparison with Mg2+. However, the presence of Sr2+ can significantly enhance the stabilization of Mg2+ on ACP due to a synergic effect. The chemical analysis reveals more Mg2+ should be excluded from ACP to initiate the crystallization of HAP when Sr2+ ions coexist in the amorphous phase. This change results in additional energy barriers for the solid phase transformation to provide a better stabilization effect on ACP, which benefit bone formation. This finding highlights the process of dopant ion exclusion in ACP and its control, which enriches our understanding on the bioinspired regulation of crystallization by using the cooperation of multiple ions.

Section: Resultssupporting

confidence: 85%

Synergic Effect of Sr²⁺and Mg²⁺on the Stabilization of Amorphous Calcium Phosphate

Jin

Liu

et al. 2018

“…As mentioned above, ACP is a precursor phase that precedes the formation of crystalline hydroxyapatite in a supersaturated calcium phosphate solution. ACP particles consist of a random assembly of ion clusters, with a Ca/P molar ratio of about 1.2 compared to the ratio of 1.67 found in stoichiometric hydroxyapatite . The ratio of 1.91 determined for the studied LbL is higher than either of these values, suggesting that, in addition to calcium phosphate, calcium oxide (CaO) forms as well.…”

Section: Resultsmentioning

confidence: 80%

“…ACP particles consist of a random assembly of ion clusters, with a Ca/P molar ratio of about 1.2 compared to the ratio of 1.67 found in stoichiometric hydroxyapatite. 51 The ratio of 1.91 determined for the studied LbL is higher than either of these values, suggesting that, in addition to calcium phosphate, calcium oxide (CaO) is forming as well. Previous studies have demonstrated that higher Ca/P ratios induce increased osteoblast adhesion, 52 but can also lower osteoblast viability.…”

mentioning

confidence: 77%

Mineralization of Layer-by-Layer Ultrathin Films Containing Microfluidic-Produced Hydroxyapatite Nanorods

Rial

Costa

Reis

et al. 2019

We describe the assembly of layer-by-layer (LbL) ultrathin films containing bioactive hydroxyapatite (HAp) rod-shaped nanoparticles with mineralizing capacity. Monodisperse 96 nm long and nm wide HAp nanorods with a surface charge of-14 mV were produced with a microfluidic system. The negatively charged HAp nanorods were assembled with the polycation poly-L-lysine (PLL) in LbL fashion. The successful deposition of alternating layers was confirmed by quartz-crystal microbalance with dissipation monitoring. The Voigtbased viscoelastic model demonstrated steady film growth where three PLL/HAp bilayers reached a thickness of 70 nm. The bioactivity of [PLL/HAp] 3 was evaluated in vitro by following the formation of a mineralized hydroxyapatite layer in simulated body fluid (SBF). X-ray diffraction, energy-dispersive X-ray spectroscopy and scanning electron microscopy (SEM) demonstrated formation of a crystalline hydroxyapatite layer and complete surface coverage within 7 days. SaOs-2 osteoblasts-like cells attached to the mineralized surfaces and developed longer filopodia extensions when compared to non-mineralized samples. Our results showed that [PLL/HAp] 3 films are feasible osteoconductive coatings applicable to orthopedic implants and fixation devices.

“…As the calculations demonstrated, the overall decrease in pH can be explained by the formation of ion pairs that changed the ratio of free phosphate species toward a lower [HPO 4 2– ] content (see Supporting Information Figure S2). The fluctuations in pH before its stabilization has previously been attributed to the possible formation of unstable clusters and solids due to local areas of high supersaturation created by the addition of calcium solution, which then immediately dissociate to establish an equilibrium. , The drop of pH below the equilibrium value followed by its fast rebound supported a similar mechanism indicating formation of highly unstable solution species and/or solid upon fast addition of calcium (Figure A). Due to the slow dehydration rate of calcium ions compared to that of phosphate species, nonequilibrium complexes with a calcium deficiency can emerge in the system for a short time interval …”

Section: Resultsmentioning

confidence: 99%

Formation of Hydroxyapatite via Transformation of Amorphous Calcium Phosphate in the Presence of Alginate Additives

Ucar

Bjørnøy

Bassett

et al. 2019

Hydroxyapatite (HA) is the primary mineral of vertebral tooth and bone tissue, thus, it is often incorporated into synthetic composite materials designed for hard tissue engineering applications.Understanding the formation mechanisms of apatitic minerals and the effects of matrix molecules during mineralization is vitally important to instruct the design of synthetic biomaterials. Here we explore the mechanism of HA formation via an amorphous calcium phosphate (ACP) precursor and the effects of alginate-based additives on the reaction progression. We found that in additive-2 free experiments the solution speciation was dominated by the classical formation of ion pairs prior to the emergence of an ACP phase, which was then followed by a transformation to HA. In the presence of alginate-based additives, ACP formation was retarded by several orders of magnitude due to kinetic hinderance and possible stabilization of intermediates, depending on the functionality of the molecules. ACP lifetime was also prolonged in the presence of additives and this stabilizing effect was associated with the surface adsorption capacity of the additives which suggests a solvent-mediated transformation mechanism. When additives with G-units were introduced in the system, the final precipitates were composed of a mixture of octacalcium phosphate (OCP) and HA via effective suppression of HA formation. Our results demonstrate that compositional variations in the additive molecules strongly influence mineralization pathways.