![Hydroxyapatite3](https://upload.wikimedia.org/wikipedia/commons/e/ea/Hydroxyapatite3.png)
Hydroxyapatite, also called hydroxylapatite (HA), is a naturally occurring
mineral
In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. ( ...
form of
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
apatite
Apatite is a group of phosphate minerals, usually hydroxyapatite, fluorapatite and chlorapatite, with high concentrations of OH−, F− and Cl− ions, respectively, in the crystal. The formula of the admixture of the three most common e ...
with the
formula
In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...
Ca
5(PO
4)
3(OH), but it is usually written Ca
10(PO
4)
6(OH)
2 to denote that the
crystal unit cell comprises two entities. Hydroxyapatite is the
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
endmember
An endmember (also end-member or end member) in mineralogy is a mineral that is at the extreme end of a mineral series in terms of purity of its chemical composition. Minerals often can be described as solid solutions with varying compositions of ...
of the complex
apatite group. The OH
− ion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...
can be replaced by
fluoride
Fluoride (). According to this source, is a possible pronunciation in British English. is an inorganic, monatomic anion of fluorine, with the chemical formula (also written ), whose salts are typically white or colorless. Fluoride salts typ ...
,
chloride
The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...
or
carbonate
A carbonate is a salt of carbonic acid (H2CO3), characterized by the presence of the carbonate ion, a polyatomic ion with the formula . The word ''carbonate'' may also refer to a carbonate ester, an organic compound containing the carbonate g ...
, producing
fluorapatite
Fluorapatite, often with the alternate spelling of fluoroapatite, is a phosphate mineral with the formula Ca5(PO4)3F (calcium fluorophosphate). Fluorapatite is a hard crystalline solid. Although samples can have various color (green, brown, bl ...
or
chlorapatite
Apatite is a group of phosphate minerals, usually hydroxyapatite, fluorapatite and chlorapatite, with high concentrations of OH−, F− and Cl− ions, respectively, in the crystal. The formula of the admixture of the three most common en ...
. It crystallizes in the
hexagonal
In geometry, a hexagon (from Greek , , meaning "six", and , , meaning "corner, angle") is a six-sided polygon. The total of the internal angles of any simple (non-self-intersecting) hexagon is 720°.
Regular hexagon
A '' regular hexagon'' has ...
crystal system
In crystallography, a crystal system is a set of point groups (a group of geometric symmetries with at least one fixed point). A lattice system is a set of Bravais lattices. Space groups are classified into crystal systems according to their po ...
. Pure hydroxyapatite powder is white. Naturally occurring apatites can, however, also have brown, yellow, or green colorations, comparable to the discolorations of
dental fluorosis
Dental fluorosis is a common disorder, characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation.
It appears as a range of visual changes in enamel causing degrees of intrinsic tooth d ...
.
Up to 50% by volume and 70% by weight of
human bone
The human skeleton is the internal framework of the human body. It is composed of around 270 bones at birth – this total decreases to around 206 bones by adulthood after some bones get fused together. The bone mass in the skeleton makes up a ...
is a modified form of hydroxyapatite, known as
bone mineral
Bone mineral (also called inorganic bone phase, bone salt, or bone apatite) is the inorganic component of bone tissue. It gives bones their compressive strength. Bone mineral is formed predominantly from carbonated hydroxyapatite with lower cry ...
. Carbonated calcium-deficient hydroxyapatite is the main mineral of which
dental enamel and
dentin
Dentin () (American English) or dentine ( or ) (British English) ( la, substantia eburnea) is a calcified tissue of the body and, along with enamel, cementum, and pulp, is one of the four major components of teeth. It is usually covered by ena ...
are composed. Hydroxyapatite crystals are also found in pathological calcifications such as those found in
breast tumors, as well as calcifications within the
pineal gland
The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep, sleep patterns in both circadian rhythm, circ ...
(and other structures of the brain) known as
corpora arenacea
Corpora arenacea (''singular'': corpus arenaceum, also called brain sand or acervuli or psammoma bodies or pineal concretions) are calcified structures in the pineal gland and other areas of the brain such as the choroid plexus. Older organisms ...
or "brain sand".
Chemical synthesis
Hydroxyapatite can be synthesized via several methods, such as wet chemical deposition, biomimetic deposition,
sol-gel route (wet-chemical precipitation) or electrodeposition. The hydroxyapatite nanocrystal suspension can be prepared by a wet chemical precipitation reaction following the reaction equation below:
10 Ca(OH)
2 + 6 H
3PO
4 → Ca
10(PO
4)
6(OH)
2 + 18 H
2O
The ability to synthetically replicate hydroxyapatite has invaluable clinical implications, especially in dentistry. Each technique yields hydroxyapatite crystals of varied characteristics, such as size and shape. These variations have a marked effect on the biological and mechanical properties of the compound, and therefore these hydroxyapatite products have different clinical uses.
Calcium-deficient hydroxyapatite
Calcium-deficient (non-stochiometric) hydroxyapatite, Ca
10−''x''(PO
4)
6−''x''(HPO
4)
''x''(OH)
2−''x'' (where ''x'' is between 0 and 1) has a Ca/P ratio between 1.67 and 1.5. The Ca/P ratio is often used in the discussion of calcium phosphate phases.
Stoichiometric apatite Ca
10(PO
4)
6(OH)
2 has a Ca/P ratio of 10:6 normally expressed as 1.67. The non-stoichiometric phases have the hydroxyapatite structure with cation vacancies (Ca
2+) and anion (OH
−) vacancies. The sites occupied solely by phosphate anions in stoichiometric hydroxyapatite, are occupied by phosphate or hydrogen phosphate, HPO
42−, anions.
Preparation of these calcium-deficient phases can be prepared by precipitation from a mixture of
calcium nitrate
Calcium nitrate, also called ''Norgessalpeter'' (Norwegian salpeter), is an inorganic compound with the formula Ca(NO3)2(H2O)x. The anhydrous compound, which is rarely encountered, absorbs moisture from the air to give the tetrahydrate. Both anhyd ...
and
diammonium phosphate
Diammonium phosphate (DAP; IUPAC name diammonium hydrogen phosphate; chemical formula (NH4)2(HPO4) is one of a series of water-soluble ammonium phosphate salts that can be produced when ammonia reacts with phosphoric acid.
Solid diammonium phosp ...
with the desired Ca/P ratio, for example, to make a sample with a Ca/P ratio of 1.6:
:9.6 Ca(NO
3)
2 + 6 (NH
4)
2HPO
4 → Ca
9.6(PO
4)
5.6(HPO
4)
0.4(OH)
1.6
Sintering these non-stoichiometric phases forms a solid phase which is an intimate mixture of tricalcium phosphate and hydroxyapatite, termed
biphasic calcium phosphate:
:Ca
10−''x''(PO
4)
6−''x''(HPO
4)
''x''(OH)
2−''x'' → (1 − ''x'') Ca
10(PO
4)
6(OH)
2 + 3''x'' Ca
3(PO
4)
2
Biological function
Mantis shrimp
The clubbing appendages of the ''
Odontodactylus scyllarus
''Odontodactylus scyllarus'', commonly known as the peacock mantis shrimp, harlequin mantis shrimp, painted mantis shrimp, clown mantis shrimp or rainbow mantis shrimp, is a large stomatopod native to the epipelagic seabed across the Indo-Pacifi ...
'' (peacock mantis shrimp) are made of an extremely dense form of the mineral which has a higher specific strength; this has led to its investigation for potential synthesis and engineering use. Their dactyl appendages have excellent
impact resistance
In materials science and metallurgy, toughness is the ability of a material to absorb energy and plastically deform without fracturing.[bone
A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...]
and
teeth
A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, tear ...
; bone is made primarily of HA crystals interspersed in a
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
matrix—65 to 70% of the mass of bone is HA. Similarly HA is 70 to 80% of the mass of
dentin
Dentin () (American English) or dentine ( or ) (British English) ( la, substantia eburnea) is a calcified tissue of the body and, along with enamel, cementum, and pulp, is one of the four major components of teeth. It is usually covered by ena ...
and
enamel in teeth. In enamel, the matrix for HA is formed by
amelogenin
Amelogenins are a group of protein isoforms produced by alternative splicing or proteolysis from the ''AMELX'' gene, on the X chromosome, and also the ''AMELY'' gene in males, on the Y chromosome. They are involved in amelogenesis, the developmen ...
s and
enamelin
Enamelin is an enamel matrix protein (EMPs), that in humans is encoded by the ''ENAM'' gene. It is part of the non- amelogenins, which comprise 10% of the total enamel matrix proteins. It is one of the key proteins thought to be involved in ame ...
s instead of collagen.
Hydroxyapatite deposits in tendons around joints results in the medical condition
calcific tendinitis
Calcific tendinitis is a common condition where calcium deposits form in a tendon, sometimes causing pain at the affected site. Deposits can occur in several places in the body, but are by far most common in the rotator cuff of the shoulder. Aro ...
.
Hydroxyapatite in remineralisation of tooth enamel
Remineralisation
In biogeochemistry, remineralisation (or remineralization) refers to the breakdown or transformation of organic matter (those molecules derived from a biological source) into its simplest inorganic forms. These transformations form a crucial link ...
of tooth enamel involves the reintroduction of mineral ions into demineralised enamel. Hydroxyapatite is the main mineral component of enamel in teeth.
During demineralisation, calcium and phosphorus ions are drawn out from the hydroxyapatite. The mineral ions introduced during remineralisation restore the structure of the hydroxyapatite crystals.
If
fluoride
Fluoride (). According to this source, is a possible pronunciation in British English. is an inorganic, monatomic anion of fluorine, with the chemical formula (also written ), whose salts are typically white or colorless. Fluoride salts typ ...
ions are present during the remineralisation, through
water fluoridation
Water fluoridation is the controlled adjustment of fluoride to a public water supply solely to reduce tooth decay. Fluoridated water contains fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding ...
or the use of fluoride-containing
toothpaste
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, a ...
, the stronger and more acid-resistant
fluorapatite
Fluorapatite, often with the alternate spelling of fluoroapatite, is a phosphate mineral with the formula Ca5(PO4)3F (calcium fluorophosphate). Fluorapatite is a hard crystalline solid. Although samples can have various color (green, brown, bl ...
crystals are formed instead of the hydroxyapatite crystals.
Use in dentistry
, the use of hydroxyapatite, or its synthetically manufactured form, nano-hydroxyapatite, is not yet common practice. Some studies suggest it is useful in counteracting dentine hypersensitivity, preventing sensitivity after teeth bleaching procedures and caries prevention.
Avian eggshell hydroxyapatite can be a viable filler material in bone regeneration procedures in oral surgery.
Dentine sensitivity
Nano-hydroxyapatite possesses bioactive components which can prompt the mineralisation process of teeth, remedying hypersensitivity. Hypersensitivity of teeth is thought to be regulated by fluid within dentinal tubules.
The movement of this fluid as a result of different stimuli is said to excite receptor cells in the pulp and trigger sensations of pain.
The physical properties of the nano-hydroxyapatite can penetrate and seal the tubules, stopping the circulation of the fluid and therefore the sensations of pain from stimuli.
Nano-hydroxyapatite would be preferred as it parallels the natural process of surface remineralisation.
In comparison to alternative treatments for dentine hypersensitivity relief nano-hydroxyapatite containing treatment has been shown to perform better clinically. Nano-hydroxyapatite was proven to be better than other treatments at reducing sensitivity against evaporative stimuli, such as an air blast, and tactile stimuli, such as tapping the tooth with a dental instrument. However, no difference was seen between nano-hydroxyapatite and other treatments for cold stimuli. Hydroxyapatite has shown significant medium and long-term desensitizing effects on dentine hypersensitivity using evaporative stimuli and the visual analogue scale (alongside potassium nitrate, arginine, glutaraldehyde with hydroxyethyl methacrylate, hydroxyapatite, adhesive systems, glass ionomer cements and laser).
Co-agent for bleaching
Teeth bleaching agents release reactive oxygen species which can degrade enamel.
To prevent this, nano-hydroxyapatite can be added to the bleaching solution to reduce the impact of the bleaching agent by blocking pores within the enamel.
This reduces sensitivity after the bleaching process.
Caries prevention
Nano-hydroxyapatite possesses a remineralising effect on teeth and can be used to prevent damage from carious attacks.
In the event of an acid attack by cariogenic bacteria, nano-hydroxyapatite particles can infiltrate pores on the tooth surface to form a protective layer.
Furthermore, nano-hydroxyapatite may have the capacity to reverse damage from carious assaults by either directly replacing deteriorated surface minerals or acting as a binding agent for lost ions.
In the future, there are possibilities for using nano-hydroxyapatite for tissue engineering and repair. The main and most advantageous feature of nano-hydroxyapatite is its biocompatibility. It is chemically similar to naturally occurring hydroxyapatite and can mimic the structure and biological function of the structures found in the resident extracellular matrix. Therefore, it can be used as a scaffold for engineering tissues such as bone and cementum.
It may be used to restore cleft lips and palates and refine existing practices such as preservation of alveolar bone after extraction for better implant placement.
As a dental material
Hydroxyapatite is widely used within dentistry and
oral and maxillofacial surgery, due to its chemical similarity to hard tissue.
In some toothpaste hydroxyapatite can be found in the form of nanocrystals (as these are easily dissolved). In recent years, hydroxyapatite nanocrystals (nHA) have been used in toothpaste to combat dental hypersensitivity. They aid in the repair and remineralisation of the
enamel, thus helping to prevent tooth sensitivity. Tooth enamel can become demineralised due to various factors, including acidic erosion and dental
caries
Tooth decay, also known as cavities or caries, is the breakdown of teeth due to acids produced by bacteria. The cavities may be a number of different colors from yellow to black. Symptoms may include pain and difficulty with eating. Complicatio ...
. If left untreated this can lead to the exposure of dentin and subsequent exposure of the
dental pulp
The pulp is the connective tissue, nerves, blood vessels, and odontoblasts that comprise the innermost layer of a tooth. The pulp's activity and signalling processes regulate its behaviour.
Anatomy
The pulp is the neurovascular bundle centr ...
. In various studies the use of nano hydroxyapatite in toothpaste showed positive results in aiding the remineralisation of dental enamel.
Synthetic hydroxyapatite (SHA) is proven to provide successful outcomes in alveolar socket preservation. Socket grafting using synthetic hydroxyapatite can result in successful bone regeneration.
Safety concerns
The
European Commission
The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...
's
Scientific Committee on Consumer Safety
The Scientific Committee on Consumer Safety (SCCS) is one of the independent scientific committees managed by the Directorate-General for Health and Consumer Protection of the European Commission, which provide scientific advice to the commission ...
(SCCS) issued an official opinion in 2021, where it considered whether the nanomaterial hydroxyapatite was safe when used in leave-on and rinse-off dermal and oral cosmetic products, taking into account reasonably foreseeable exposure conditions. It stated:
Chromatography
The mechanism of hydroxyapatite
chromatography
In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...
is complicated and has been described as "mixed-mode". It involves ionic interactions between positively charged groups on a biomolecule (often a protein) and the phosphate groups in hydroxyapatite, and metal chelation between hydroxyapatite calcium ions and negatively charged phosphate and/or carboxyl groups on the biomolecule. It may be difficult to predict the effectiveness of hydroxyapatite chromatography based on physical and chemical properties of the desired protein to be purified. For elution, a buffer with increasing phosphate and/or neutral salt concentration is typically used.
Use in archaeology
In
archaeology
Archaeology or archeology is the scientific study of human activity through the recovery and analysis of material culture. The archaeological record consists of artifacts, architecture, biofacts or ecofacts, sites, and cultural landscap ...
, hydroxyapatite from
human and animal remains can be analysed to reconstruct ancient
diets
The Low Countries comprise the coastal Rhine–Meuse–Scheldt delta region in Western Europe, whose definition usually includes the modern countries of Luxembourg, Belgium and the Netherlands. Both Belgium and the Netherlands derived their ...
, migrations and paleoclimate. The mineral fractions of bone and teeth act as a reservoir of
trace elements
__NOTOC__
A trace element, also called minor element, is a chemical element whose concentration (or other measure of amount) is very low (a "trace amount"). They are classified into two groups: essential and non-essential. Essential trace elements ...
, including carbon, oxygen and strontium. Stable isotope analysis of human and faunal hydroxyapatite can be used to indicate whether a diet was predominantly terrestrial or marine in nature (carbon, strontium); the geographical origin and migratory habits of an animal or human (oxygen, strontium) and to reconstruct past temperatures and climate shifts (oxygen). Post-depositional alteration of bone can contribute to the degradation of bone collagen, the protein required for stable isotope analysis.
Defluoridation
Hydroxyapatite is a potential
adsorbent
Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a ...
for the
defluoridation Defluoridation is the downward adjustment of the level of fluoride in drinking water. Worldwide, fluoride is one of the most abundant anions present in groundwater. Fluoride is more present in groundwater than surface water mainly due to the leachin ...
of
drinking water
Drinking water is water that is used in drink or food preparation; potable water is water that is safe to be used as drinking water. The amount of drinking water required to maintain good health varies, and depends on physical activity level, a ...
, as it forms
fluorapatite
Fluorapatite, often with the alternate spelling of fluoroapatite, is a phosphate mineral with the formula Ca5(PO4)3F (calcium fluorophosphate). Fluorapatite is a hard crystalline solid. Although samples can have various color (green, brown, bl ...
in a three step process. Hydroxyapatite removes F
− from the water to replace OH
− forming fluorapatite. However, during the defluoridation process the hydroxyapatite dissolves, and increases the
pH and
phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phospho ...
ion concentration which makes the defluoridated water unfit for drinking.
Recently, a ″calcium amended-hydroxyapatite″ defluoridation technique was suggested to overcome the phosphate leaching from hydroxyapatite.
This technique can also affect fluorosis reversal by providing calcium-enriched alkaline drinking water to fluorosis affected areas.
See also
*
Calcium hydroxyphosphate
*
Calcific tendinitis
Calcific tendinitis is a common condition where calcium deposits form in a tendon, sometimes causing pain at the affected site. Deposits can occur in several places in the body, but are by far most common in the rotator cuff of the shoulder. Aro ...
*
Mechanical properties of biomaterials Materials that are used for biomedical or clinical applications are known as biomaterials. The following article deals with fifth generation biomaterials that are used for bone structure replacement. For any material to be classified for biomedical ...
References
External links
{{Authority control
Calcium minerals
Phosphate minerals
Ceramic materials
Biomaterials
Hexagonal minerals
Minerals in space group 176