Interaction of Citric Acid with Hydroxyapatite: Surface Exchange of Ions and Precipitation of Calcium Citrate

Misra, D.N.

doi:10.1177/00220345960750061401

Cited by 69 publications

(42 citation statements)

References 20 publications

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“…Given that a citrate molecule has a geometrical area of ca. 0.65 nm 2 (25), citrate covers about 1∕6 of the available apatite surface area in bone.…”

Section: Resultsmentioning

confidence: 99%

Strongly bound citrate stabilizes the apatite nanocrystals in bone

Rawal

Schmidt‐Rohr

2010

Proc. Natl. Acad. Sci. U.S.A.

472

495

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Nanocrystals of apatitic calcium phosphate impart the organicinorganic nanocomposite in bone with favorable mechanical properties. So far, the factors preventing crystal growth beyond the favorable thickness of ca. 3 nm have not been identified. Here we show that the apatite surfaces are studded with strongly bound citrate molecules, whose signals have been identified unambiguously by multinuclear magnetic resonance (NMR) analysis. NMR reveals that bound citrate accounts for 5.5 wt% of the organic matter in bone and covers apatite at a density of about 1 molecule per ð2 nmÞ 2 , with its three carboxylate groups at distances of 0.3 to 0.45 nm from the apatite surface. Bound citrate is highly conserved, being found in fish, avian, and mammalian bone, which indicates its critical role in interfering with crystal thickening and stabilizing the apatite nanocrystals in bone.T he load-bearing material in bone is a fascinating organicinorganic nanocomposite whose stiffness is provided by thin nanocrystals of carbonated apatite, a calcium phosphate, imbedded in an organic matrix consisting mostly of collagen, a fibrous protein (1-5). The small (ca. 3-nm) thickness of the apatite nanocrystals is favorable for mechanical properties, likely preventing crack propagation (6). While the size and shape of the nanocrystals have been studied extensively (4, 5), the mechanism stabilizing them at a thickness corresponding to only about four unit cells has not been elucidated. A better understanding of the factors controlling the nanocrystals in bone is desirable for prevention and treatment of bone diseases such as osteoporosis, which causes millions of fractures each year (7), and for more efficient synthesis of biomimetic nanocomposites (8, 9). In vitro experiments have shown that carboxylate-rich proteins such as osteocalcin and osteopontin (7) can affect hydroxyapatite crystal formation and growth (10, 11). These observations might suggest that such proteins limit nanocrystal thickening (12); however, these proteins are not sufficiently abundant in vivo to bind to all the nanocrystal surfaces at high enough area concentration; possibly, they control the length of the nanocrystals (7).Here we show instead that the surfaces of the apatite crystals in bone are studded with strongly bound citrate molecules, at a density of ca. 1∕ð2 nmÞ 2 , using advanced solid-state nuclear magnetic resonance (NMR) as a unique tool for probing buried interfaces. Citrate is quite abundant in bone (ca. 1 wt%, or 5 wt% of the organic components) (13,14). Before 1975, citrate in bone was studied by simple wet-chemical methods and thought to regulate bone demineralization (14). However, citrate is no longer even mentioned in most of the prominent literature on the bone nanocomposite published during the last thirty years (1)(2)(3)(4)(5)(15)(16)(17)(18). We now highlight the importance of citrate in bone by demonstrating that it is not a dissolved calcium-solubilizing agent but a strongly bound, integral part of the nanocomposite. Structurally, citrate s...

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“…Given that a citrate molecule has a geometrical area of ca. 0.65 nm 2 (25), citrate covers about 1∕6 of the available apatite surface area in bone.…”

Section: Resultsmentioning

confidence: 99%

Strongly bound citrate stabilizes the apatite nanocrystals in bone

Rawal

Schmidt‐Rohr

2010

Proc. Natl. Acad. Sci. U.S.A.

472

495

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“…27 Citric acid revealed areas of intense CF marker signals and areas of a lower presence of gold particles; this can be related to a nonuniform demineralization due to the buffering of acidic potential by dissolved mineral components. 28,29 On the other hand, the appearance of the CFs after phosphoric acid etching was characterized by a very uniform labeling pattern on the dentin caused by the major aggressiveness of phosphoric acid (at 35%). 31 The lower labeling intensity of phosphoric acid compared to that of organic acids may depend on the aggressiveness of phosphoric acid and its effect on the structural integrity of the CFs, as previously reported after prolonged application of phosphoric acid.…”

Section: Discussionmentioning

confidence: 99%

Immunocytochemical analysis of dentin: A double‐labeling technique

Breschi

Gobbi

Lopes

et al. 2003

J Biomedical Materials Res

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Immunocytochemical analysis is a fundamental and selective technique for identifying different molecular components of human dental structure. The hypothesis tested here is that the application of different etching solutions on dentin does not hinder collagen fibrils and proteoglycans from maintaining their immunochemical antigenicity. Human dentin disks were treated with 0.5M of EDTA, citric acid, maleic acid, or phosphoric acid (for 15 or 30 s). A double-immunolabeling technique was performed to identify, simultaneously, collagen fibrils and chondroitin sulfate. The use of different acids resulted in different degrees of labeling. Maleic and citric acids revealed a diffuse and intense labeling for both collagen fibrils and proteoglycans. The use of phosphoric acid on dentin showed a massive coagulation of the proteoglycans (15 s) or very low labeling (30 s). These data clarify that the use of acids on dentin components is able to modify their antigenicity. Moreover, the double-labeling immunocytochemical technique allows understanding of the spatial relationships between the collagen fibrils and proteoglycans of the dentin matrix.

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“…40 The reaction of chlorhexidine digluconate is shown in Figure 6, and the uptake curves with time can be interpreted on the basis of the solubility of chlorhexidine phosphate, the salt that slowly precipitates out of the solution. 23 The interaction of citric acid 41 and o-phospho-l-serine 42 with hydroxyapatite can also be explained on the basis of the analysis of adsorbate-uptake, the concentrations of calcium and phosphate ions in solution, and their mutual ratios. In both cases, there is an ion-exchange adsorption from dilute concentrations.…”

Section: ϫmentioning

confidence: 99%

“…For dilute concentrations, there is an ion-exchange adsorption, and the territorial domain of the ions is determined by the lattice forces of the substrate. Even for ionic adsorption at dilute concentrations, if the ions are big, the domain may be determined by the size of the ions (e.g., citrate 41 and o-phospho-l-serine 42 ions).…”

Section: ϫmentioning

confidence: 99%

Adsorption from solutions on synthetic hydroxyapatite: Nonaqueous vs. aqueous solvents

Misra¹

1999

J. Biomed. Mater. Res.

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It is useful in restorative dentistry and etiology of bone diseases to know that certain general rules may be derived from a priori considerations of the adsorption of chemicals to synthetic hydroxyapatite (which is the structural prototype of tooth and bone mineral). This article systematically synthesizes the extensive studies on the subject by the author, and rationalizes and extends these rules. Though not a review article, the work of some researchers may not have found an adequate representation here, because they did not determine, in the case of nonaqueous solvents, the reversibility of adsorption; or, in the case of aqueous solvents, the concentration of all constituent ions of the system, thus missing the occurrence of processes other than adsorption. The adsorption of solutes from nonaqueous solvents on hydroxyapatite is mainly regulated by the interplay of hydrogen bonding between adsorbate, adsorbent, and solvent. It does not involve any significant role of ionic nature of the apatite surface, because it is masked by the chemisorbed and physisorbed water. This interplay of hydrogen bonding in conjunction with chemical and structural characteristics of the adsorbed molecules controls their reversibility and the orientation of the adsorbates on the surface. In general, the process may be considered as true adsorption, because no other material exchange process is involved. The "adsorption" of solutes from aqueous solutions generally involves ion-exchange with the apatite surface, and may be affected by the concentrations of potential determining ions (Ca(2+), phosphates, H(+), etc.) in the solution. The solute in aqueous solution may be removed by two other mechanisms, either by formation of a surface complex or by chemically reacting with calcium or phosphate ions to form a new phase that precipitates out of solution. Therefore, the concentration of calcium and phosphate ions in solution should also be monitored to elucidate the mechanism of the process. Adsorption of polymers seems to be determined primarily by their multiple hydrogen bonding, their relative molar mass, and their ability to self-associate. The hydrogen ion concentration plays a decisive role in each one of the above mechanisms.

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Interaction of Citric Acid with Hydroxyapatite: Surface Exchange of Ions and Precipitation of Calcium Citrate

Cited by 69 publications

References 20 publications

Strongly bound citrate stabilizes the apatite nanocrystals in bone

Strongly bound citrate stabilizes the apatite nanocrystals in bone

Immunocytochemical analysis of dentin: A double‐labeling technique

Adsorption from solutions on synthetic hydroxyapatite: Nonaqueous vs. aqueous solvents

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