Amorphous calcium phosphate

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Amorphous calcium phosphate (ACP or ATCP) is a glassy precipitate of variable composition that is formed in double decomposition reactions involving a soluble phosphate and calcium salts (e.g. (NH4)2HPO4 + Ca(NO3)2) [1] performed under carefully controlled pH conditions. Such a mixture is also known as calcium phosphate cement. [2] The precipitate will either be "amorphous tricalcium phosphate", ATCP, or calcium deficient hydroxyapatite, CDHA, Ca9(HPO4)(PO4)5(OH), (note that CDHA is sometimes termed apatitic calcium triphosphate). [1] [3] [4] The composition of amorphous calcium phosphate is CaxHy(PO4)z·nH2O, where n is between 3 and 4.5. [4] Precipitation from the moderately supersaturated and basic solution containing magnesium produces amorphous magnesium calcium phosphate (AMCP) in which magnesium incorporated into the ACP structure. [5]


A commercial preparation of ACP is casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), derived from cow milk. It is sold under various brand names including Recaldent and Tooth Mousse, intended to be applied directly on teeth. Its clinical usefulness is unknown. [6]

Biogenic ACP

Biogenic ACP has been found in the inner ear of embryonic sharks, mammalian milk and dental enamel. However, whilst the unequivocal presence of ACP in bones and teeth is the subject of debate, there is evidence that transient amorphous precursors are involved in the development of bone and teeth. [4] The ACP in bovine milk (CPP-ACP) is believed to involve calcium phosphate nanoclusters covered in a shell of casein phosphopeptides. A typical casein micelle of radius 100 nm contains around 10,000 casein molecules and 800 nanoclusters of ACP, each of an approximate diameter of 4.8 nm. The concentration of calcium phosphate is higher in milk than in serum, but it rarely forms deposits of insoluble phosphates. [7] Unfolded phosphopeptides are believed to sequester ACP nanoclusters, [8] and form stable complexes in other biofluids such as urine and blood serum, thus preventing deposition of insoluble calcium phosphates and calcification of soft tissue. In the laboratory, stored samples of formulations of artificial blood, serum, urine and milk (which approximate the pH of the naturally occurring fluid) deposit insoluble phosphates. The addition of suitable phosphopeptides prevents precipitation. [7]

Posner's clusters

Following investigations into the composition of amorphous calcium phosphates precipitated under different conditions, Posner and Betts suggested in the mid 1970s that the structural unit of ACP was a neutral cluster Ca9(PO4)6. [4] Calculations support the description of a cluster with central Ca2+ ion surrounded by six phosphate PO43− anions, which in turn are surrounded by eight further calcium ions. [9] The resulting cluster is estimated to have a diameter of around 950 pm (0.95 nm). These are now generally referred to as Posner's clusters. Precipitated ACP is believed to be made up of particles containing a number of Posner's clusters with water in the intervening spaces. While plasma spray coated ACP may contain Posner's clusters, there cannot be any water present. [4]

Use in dental treatment

Amorphous calcium phosphate in combination with casein phosphopeptide has been used as a dental treatment to treat incipient dental decay. ACP sees its main use as an occluding agent, which aids in reducing sensitivity. Studies have shown that it does form a remineralized phase of hydroxyapatite consistent with the natural enamel.[ citation needed ] In addition, clinical studies have shown that patients who whiten their teeth have reduced sensitivity after treatment. [10] It is believed that ACP hydrolyzes under physiological temperatures and pH to form octacalcium phosphate as an intermediate, and then surface apatite.

Method of mineralization

ACP lacks the long-range, periodic atomic-scale order of crystalline calcium phosphates. The X-ray diffraction pattern is broad and diffuse with a maximum at 25 degree 2 theta[ clarify ], and no other different features compared with well-crystallized hydroxyapatite. Under electron microscopy, its morphological form is shown as small spheroidal particles in the scale of tenths nanometer. In aqueous media, ACP is easily transformed into crystalline phases such as octacalcium phosphate and apatite due to the growing of microcrystallites. It has been demonstrated that ACP has better osteoconductivity and biodegradability than tricalcium phosphate and hydroxyapatite in vivo. [11]

Moreover, it can increase alkaline phosphatase activities of mesoblasts, enhance cell proliferation and promote cell adhesion. The unique role of ACP during the formation of mineralized tissues makes it a promising candidate material for tissue repair and regeneration. ACP may also be a potential remineralizing agent in dental applications. Recently developed ACP-filled bioactive composites are believed to be effective anti-demineralizing/remineralizing agents for the preservation and repair of tooth structures. [11]

See also

Related Research Articles

Casein pronounced "kay-seen", is a family of related phosphoproteins. These proteins are commonly found in mammalian milk, comprising c. 80% of the proteins in cow's milk and between 20% and 45% of the proteins in human milk. Sheep and buffalo milk have a higher casein content than other types of milk with human milk having a particularly low casein content.

Toothpaste paste or gel dentifrice used to clean and maintain the health of teeth

Toothpaste is a paste or gel dentifrice used with a toothbrush to clean and maintain the aesthetics and health of teeth. Toothpaste is used to promote oral hygiene: it is an abrasive that aids in removing dental plaque and food from the teeth, assists in suppressing halitosis, and delivers active ingredients to help prevent tooth decay and gum disease (gingivitis). Salt and sodium bicarbonate are among materials that can be substituted for commercial toothpaste. Large amounts of swallowed toothpaste can be toxic.

Tooth enamel outer tooth tissue

Tooth enamel is one of the four major tissues that make up the tooth in humans and many other animals, including some species of fish. It makes up the normally visible part of the tooth, covering the crown. The other major tissues are dentin, cementum, and dental pulp. It is a very hard, white to off-white, highly mineralised substance that acts as a barrier to protect the tooth but can become susceptible to degradation, especially by acids from food and drink. In rare circumstances enamel fails to form, leaving the underlying dentin exposed on the surface.

Tooth decay disease involving breakdown of teeth

Tooth decay, also known as dental caries or cavities, is a breakdown of teeth due to acids made by bacteria. The cavities may be a number of different colors from yellow to black. Symptoms may include pain and difficulty with eating. Complications may include inflammation of the tissue around the tooth, tooth loss, and infection or abscess formation.

Ultrastructure the nanostructure of a biological specimen that can be viewed with ultramicroscopy or electron microscopy

Ultrastructure is the architecture of cells and biomaterials that is visible at higher magnifications than found on a standard optical light microscope. This traditionally meant the resolution and magnification range of a conventional transmission electron microscope (TEM) when viewing biological specimens such as cells, tissue, or organs. Ultrastructure can also be viewed with scanning electron microscopy and super-resolution microscopy, although TEM is a standard histology technique for viewing ultrastructure. Such cellular structures as organelles, which allow the cell to function properly within its specified environment, can be examined at the ultrastructural level.

Calcium phosphate is a family of materials and minerals containing calcium ions (Ca2+) together with inorganic phosphate anions. Some so-called calcium phosphates contain oxide and hydroxide as well. They are white solids of nutritious value. Calcium phosphates are found in many living organisms, e.g., bone mineral and tooth enamel. In milk, it exists in a colloidal form in micelles bound to casein protein with magnesium, zinc, and citrate - collectively referred to as colloidal calcium phosphate (CCP). Various calcium phosphate minerals are used in the production of phosphoric acid and fertilizers. Overuse of certain forms of calcium phosphate can lead to nutrient-containing surface runoff and subsequent adverse effects upon receiving waters such as algal blooms and eutrophication.

Hydroxyapatite phosphate mineral

Hydroxyapatite, also called hydroxylapatite (HA), is a naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but it is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities. Hydroxyapatite is the hydroxyl endmember of the complex apatite group. The OH ion can be replaced by fluoride, chloride or carbonate, producing fluorapatite or chlorapatite. It crystallizes in the hexagonal crystal system. Pure hydroxyapatite powder is white. Naturally occurring apatites can, however, also have brown, yellow, or green colorations, comparable to the discolorations of dental fluorosis.

An anticaking agent is an additive placed in powdered or granulated materials, such as table salt or confectioneries, to prevent the formation of lumps (caking) and for easing packaging, transport, flowability, and consumption. Caking mechanisms depend on the nature of the material. Crystalline solids often cake by formation of liquid bridge and subsequent fusion of microcrystals. Amorphous materials can cake by glass transitions and changes in viscosity. Polymorphic phase transitions can also induce caking.

Tricalcium phosphate chemical compound Ca₃O₈P₂

Tricalcium phosphate (sometimes abbreviated TCP) is a calcium salt of phosphoric acid with the chemical formula Ca3(PO4)2. It is also known as tribasic calcium phosphate and bone phosphate of lime (BPL). It is a white solid of low solubility. Most commercial samples of "tricalcium phosphate" are in fact hydroxyapatite.

Dicalcium phosphate chemical compound CaHPO₄

Dicalcium phosphate is the calcium phosphate with the formula CaHPO4 and its dihydrate. The "di" prefix in the common name arises because the formation of the HPO42– anion involves the removal of two protons from phosphoric acid, H3PO4. It is also known as dibasic calcium phosphate or calcium monohydrogen phosphate. Dicalcium phosphate is used as a food additive, it is found in some toothpastes as a polishing agent and is a biomaterial.

A glass ionomer cement is a dental restorative material used in dentistry as a filling material and luting cement, including for orthodontic bracket attachment. Glass-ionomer cements are based on the reaction of silicate glass-powder and polyacrylic acid, an ionomer. Occasionally water is used instead of an acid, altering the properties of the material and its uses. This reaction produces a powdered cement of glass particles surrounded by matrix of fluoride elements and is known chemically as glass polyalkenoate. There are other forms of similar reactions which can take place, for example, when using an aqueous solution of acrylic/itaconic copolymer with tartaric acid, this results in a glass-ionomer in liquid form. An aqueous solution of maleic acid polymer or maleic/acrylic copolymer with tartaric acid can also be used to form a glass-ionomer in liquid form. Tartaric acid plays a significant part in controlling the setting characteristics of the material. Glass-ionomer based hybrids incorporate another dental material, for example resin-modified glass ionomer cements (RMGIC) and compomers.

Remineralisation of teeth

Tooth remineralisation is the natural repair process for non-cavitated tooth lesions, in which calcium, phosphate and sometimes fluoride ions are deposited into crystal voids in demineralised enamel. Remineralisation can contribute towards restoring strength and function within tooth structure.


Bioceramics and bioglasses are ceramic materials that are biocompatible. Bioceramics are an important subset of biomaterials. Bioceramics range in biocompatibility from the ceramic oxides, which are inert in the body, to the other extreme of resorbable materials, which are eventually replaced by the body after they have assisted repair. Bioceramics are used in many types of medical procedures. Bioceramics are typically used as rigid materials in surgical implants, though some bioceramics are flexible. The ceramic materials used are not the same as porcelain type ceramic materials. Rather, bioceramics are closely related to either the body's own materials or are extremely durable metal oxides.

Amorphous calcium carbonate

Amorphous calcium carbonate (ACC) is the amorphous and least stable polymorph of calcium carbonate. ACC is extremely unstable under normal conditions and is found naturally in taxa as wide-ranging as sea urchins, corals, mollusks, and foraminifera. It is usually found as a monohydrate, holding the chemical formula CaCO3·H2O; however, it can also exist in a dehydrated state, CaCO3. ACC has been known to science for over 100 years when a non-diffraction pattern of calcium carbonate was discovered by Sturcke Herman, exhibiting its poorly-ordered nature.

Pulp capping

Pulp capping is a technique used in dental restorations to prevent the dental pulp from necrosis, after being exposed, or nearly exposed during a cavity preparation. When dental caries is removed from a tooth, all or most of the infected and softened enamel and dentin are removed. This can lead to the pulp of the tooth either being exposed or nearly exposed which causes pulpitis (inflammation). Pulpitis, in turn, can become irreversible, leading to pain and pulp necrosis, and necessitating either root canal treatment or extraction. The ultimate goal of pulp capping or stepwise caries removal is to protect a healthy dental pulp and avoid the need for root canal therapy.

Tetracalcium phosphate is the compound Ca4(PO4)2O, (4CaO.P2O5). It is the most basic of the calcium phosphates, and has a Ca/P ratio of 2, making it the most phosphorus poor phosphate. It is found as the mineral hilgenstockite, which is formed in industrial phosphate rich slag (called "Thomas slag"). This slag was used as a fertiliser due to the higher solubility of tetracalcium phosphate relative to apatite minerals. Tetracalcium phosphate is a component in some calcium phosphate cements that have medical applications.

Oligopeptide P11-4

P11-4 is a synthetic, pH controlled self-assembling peptide used for biomimetic mineralization e.g. for enamel regeneration or as an oral care agent. P11-4 consists of the natural occurring amino acids Glutamine, Glutamic acid, Phenylalanine, Tryptophan and Arginine. The resulting higher molecular structure has a high affinity to tooth mineral. P11-4 has been developed and patented by The University of Leeds, (UK). The swiss company credentis has licensed the peptide technology and markets it under the trade names including CUROLOX, REGENAMEL, and EMOFLUOR. They offer three products with this technology. As of June 2016 in Switzerland products are available with new Brand names from Dr. Wild & Co AG.

Sour cream dairy product produced by fermenting a regular cream with certain kinds of lactic acid bacteria

Sour cream or soured cream is a dairy product obtained by fermenting regular cream with certain kinds of lactic acid bacteria. The bacterial culture, which is introduced either deliberately or naturally, sours and thickens the cream. Its name comes from the production of lactic acid by bacterial fermentation, which is called souring.

Periodontal disease, also known as oral disease, is one of the most common diseases found in dogs and cats. It is caused by the buildup of various anaerobic bacteria in the mouth which forms plaque, eventually hardening into tartar on the teeth along the gum line, and is related to the development of gingivitis. Since small and toy breeds have a much smaller jaw but contain the same number of teeth, crowding allows higher bacterial build up and puts them at higher risk of developing periodontal disease.

Molar incisor hypomineralisation human disease

Molar incisor hypomineralisation (MIH) is a type of enamel defect affecting, as the name suggests, the first molars and incisors in the permanent dentition. MIH is considered a worldwide problem and usually occurs in children under 10 years old. This developmental condition is caused by the lack of mineralisation of enamel during its maturation phase, due to interruption to the function of ameloblasts. Many factors have been suggested, such as genetics and medical problems during pregnancy, but only childhood illness, fever in particular, seems to be associated with MIH. However, further studies on the aetiology of MIH are required because it is believed to be multifactorial.


  1. 1 2 Destainville, A., Champion, E., Bernache-Assollant, D., Laborde, E. (2003). "Synthesis, characterization and thermal behavior of apatitic tricalcium phosphate". Materials Chemistry and Physics. 80 (1): 269–277. doi:10.1016/S0254-0584(02)00466-2. ISSN   1742-7061.CS1 maint: uses authors parameter (link)  via ScienceDirect  (Subscription may be required or content may be available in libraries.)
  2. Al-Sanabani, JS; Madfa, AA; Al-Sanabani, FA (2013). "Application of calcium phosphate materials in dentistry". International Journal of Biomaterials. 2013: 876132. doi:10.1155/2013/876132. PMC   3710628 . PMID   23878541.
  3. Rey, C.; Combes, C.; Drouet, C.; Grossin, D. (2011). "1.111. Bioactive Ceramics: Physical Chemistry". In Ducheyne, Paul (ed.). Comprehensive Biomaterials. 1. Elsevier. pp. 187–281. doi:10.1016/B978-0-08-055294-1.00178-1. ISBN   978-0-08-055294-1.  via ScienceDirect  (Subscription may be required or content may be available in libraries.)
  4. 1 2 3 4 5 Dorozhkin, Sergey V. (December 2012). "Amorphous calcium (ortho)phosphates". Acta Biomaterialia. 6 (12): 4457–4475. doi:10.1016/j.actbio.2010.06.031. ISSN   1742-7061. PMID   20609395.CS1 maint: uses authors parameter (link)  via ScienceDirect  (Subscription may be required or content may be available in libraries.)
  5. Babaie, Elham; Zhou, Huan; Lin, Boren; Bhaduri, Sarit B. (August 2015). "Influence of ethanol content in the precipitation medium on the composition, structure and reactivity of magnesium–calcium phosphate". Materials Science and Engineering: C. 53: 204–211. doi:10.1016/j.msec.2015.04.011. PMID   26042708.
  6. Hani, Thikrayat Bani; O'Connell, Anne C.; Duane, Brett (24 June 2016). "Casein phosphopeptide-amorphous calcium phosphate products in caries prevention". Evidence-Based Dentistry. 17 (2): 46–47. doi:10.1038/sj.ebd.6401168. PMID   27339237.
  7. 1 2 Holt, Carl (June 2013). "Unfolded phosphopolypeptides enable soft and hard tissues to coexist in the same organism with relative ease". Current Opinion in Structural Biology. 23 (3): 420–425. doi:10.1016/ ISSN   0959-440X. PMID   23622834.CS1 maint: uses authors parameter (link)  via ScienceDirect  (Subscription may be required or content may be available in libraries.)
  8. Holt, Carl; Sørensen, Esben S.; Clegg, Roger A. (2009). "Role of calcium phosphate nanoclusters in the control of calcification". FEBS Journal. 276 (8): 2308–2323. doi:10.1111/j.1742-4658.2009.06958.x. ISSN   1742-464X. PMID   19292864.
  9. Kanzaki, Noriko; Treboux, Gabin; Onuma, Kazuo; Tsutsumi, Sadao; Ito, Atsuo (November 2011). "Calcium phosphate clusters". Biomaterials. 22 (21): 2921–2929. doi:10.1016/S0142-9612(01)00039-4. ISSN   0142-9612. PMID   11561898.CS1 maint: uses authors parameter (link)  via ScienceDirect  (Subscription may be required or content may be available in libraries.)
  10. Van Haywood, B (2002). "Dentine hypersensitivity: bleaching and restorative considerations for successful management". International Dental Journal. 52: 376–384. doi:10.1002/j.1875-595x.2002.tb00937.x.
  11. 1 2 Zhao, J.; Liu, Y.; Sun, W. B.; Zhang, H. (2011). "Amorphous calcium phosphate and its application in dentistry". Chem. Cent. J. 5: 40. doi:10.1186/1752-153X-5-40. PMC   3143077 . PMID   21740535.