Synergistic interplay between the two major bone minerals, hydroxyapatite and whitlockite nanoparticles, for osteogenic differentiation of mesenchymal stem cells.

The inorganic part of human bone is mainly composed of hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) minerals, where the WH phase occupies up to 20-35% of total weight. These two bone minerals have different crystal structures and physicochemical properties, implying their distinguished role in bone physiology. However, until now, the biological significance of the presence of a certain ratio between HAP and WH in bone is unclear. To address this fundamental question, bone mimetic scaffolds are designed to encapsulate human mesenchymal stem cells (MSCs) for assessing their osteogenic activity depending on different ratios of HAP and WH. Interestingly, cellular growth and osteogenic differentiation are significantly promoted when MSCs are grown with a 3-1 ratio of HAP and WH nanoparticles, which is similar to bone. One of the reasons for this synergism between HAP and WH in hydrogel scaffolds is that, while WH nanoparticles can enhance osteogenic differentiation of MSCs compared to HAP, WH counterintuitively decreases the mechanical stiffness of nanocomposite hydrogels and hinders the osteogenic activity of cells. Taken together, these findings identify the optimal ratio between two major minerals in bone mimetic scaffolds to maximize the osteogenic differentiation of MSCs. STATEMENT OF SIGNIFICANCE: Human bone minerals are composed of HAP and WH inorganic nanoparticles which have different material properties. However, the reason for the coexistence of HAP and WH in human bone is not fully identified, and HAP and WH composite biomaterial has not been utilized in the clinic. In this study, we have developed bone mimetic HAP and WH nanocomposite hydrogel scaffolds with various ratios. Importantly, we found out that HAP can promote the mechanical stiffness of the composite hydrogel scaffolds while WH can enhance the osteogenic activity of stem cells, which together induced synergism to maximize osteogenic differentiation of stem cells when mixed into 3-1 ratio that is similar to human bone.

Plaque mineral induction and inhibition properties in the formation of supragingival calculus.

Several individual species of dental plaque bacteria have the ability to initiate the precipitation of calcium phosphate minerals in vitro; other plaque components have been shown to inhibit mineralisation. We have examined subjects' overall plaque mineralisation promoter and inhibitor properties, and have attempted to correlate them with supragingival calculus development over 6 months. Three-day-old plaque was collected from 22 adult subjects at the start and end of the study. To detect promoter activity, the plaque was placed in a suspension of brushite, the liquid phase of which was supersaturated with respect to hydroxyapatite. The extent of mineralisation was determined by the rise in phosphate concentration over 4 days. To detect inhibitor activity, plaque was placed in a similar suspension, which also contained hydroxyapatite. Promoter activity was compared with that hydroxyapatite, and inhibitor activity was compared with polyaspartate. The subjects' teeth were scaled at the start of the study, and calculus deposition was measured at the end using the Volpe Manhold method. Most plaque samples showed some promoter or inhibitor activity, or both, but no significant correlation existed between these activities and a subject's development of calculus. A significant inverse correlation existed between plaque mineralisation promoter activity and its inhibitor activity at the start of the study. Our results suggest that the nucleating and mineralisation inhibitory properties of young plaque will probably not be a useful target for a practical preventive methodology for supragingival calculus.