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ABSTRACT: Hydroxyapatite (HAp) is the emerging most bioceramic, which is widely used in various biomedical
applications, mainly in orthopedics and dentistry due to its close similarities with inorganic mineral component of bone
and teeth. Synthetic HAp is known to be similar to naturally occurring HAp on the basis of crystallographic and
chemical studies. Several methodologies have been investigated and developed for the synthesis of HAp. But, new
economic and versatile methods for HAp synthesis are of interest due to its immense importance and wide utilization in
biomedical applications. This review presents various well known methodologies for HAp synthesis like precipitation
technique, sol-gel approach, hydrothermal technique, multiple emulsion technique, biomimetic deposition technique,
electrodeposition technique etc.
Key words: Hydroxyapatite; Bioceramic; Precipitation technique; Sol-gel approach; Biomimetic deposition
INTRODUCTION
During past few decades, considerable offers high binding affinity for a variety of
research efforts have been directed towards the pharmacological substances such as antibiotics,
synthesis of various bioceramics for biomedical hormones, enzymes, antibody fragments, steroids etc9-
14
applications. Among different classes of bioceramics, . This has opened the potential for using synthetic
hydroxyapatite (HAp) is the emerging most HAp to deliver pharmacological substances in many
bioceramic, which is widely used in various clinical applications with sustained release capacity for
biomedical applications, mainly in orthopedics and the treatment of osteomyelitis, osteoporosis, osseous
dentistry. HAp has close similarities with inorganic cancers etc in which local delivery is effective with the
mineral component of bone and teeth1. It possesses need to fill defects in the skeleton. New economic and
exceptional biocompatibility and unique bioactivity2-4. versatile methods for HAp synthesis are of interest due
Naturally occurring HAp is hexagonal in structure with to the importance of this material for various
the chemical formula of one unit cell being biomedical applications. The current communication
Ca10(PO4)6(OH)2 5. The hydroxyl ion (OH-) od it can deals with various methodologies for the preparation
be replaced by F-, Cl-, CO32-, etc in the collagen fiber of synthetic HAp with optimum properties closer to
matrix. those of living hard tissues like bone and teeth, aiming
Synthetic HAp is known to be similar to at better and more effective biomedical applications.
naturally occurring HAp on the basis of
crystallographic and chemical studies6. Because, METHODS FOR HAp SYNTHESIS
synthetic HAp is thermodynamically stable at Several methods have been utilized for the
physiological pH5 and osteoconductive, it has been synthesis of HAp include precipitation technique15-17,
widely used in hard tissue replacement and sol-gel approach18, hydrothermal technique19, multiple
reconstruction applications, such as implant coatings7, emulsion technique20, biomimetic deposition
and bone substitues8 etc. Its porous character also 21-22 23
technique , electrodeposition technique etc.
Amit Kumar Nayak /Int.J. ChemTech Res.2010,2(2) 904
calcium acetate and triethyl phosphate in water and Table 1: Ion concentrations of SBF solutions22
ethanol medium. Haddow et al35 used calcium acetate Ions Concentration, mM
together with various phosphorous precursors, i.e.
phosphoric acid [H3PO4], phosphorous pentoxide Na+ 142.00
[P2O5] and triethyl phosphite for HAp coating. Among Cl-
125.00
them, the HAp coating using calcium acetate and
triethyl phosphate showed the best result. The HCO3- 27.00
temperature required to form an apatite phase was > K +
5.00
600C Ca2+ 2.50
Hydrothermal technique: HPO42- 1.00
In the 20th century, the hydrothermal technique SO22- 0.50
for synthesis of materials was clearly identified as an 2+
important technology36 and using this technology Mg 1.50
various ceramic materials including HAp can be
synthesized. Hydrothermal synthesis is a process that The SBF is prepared according to the chemical
utilizes single or heterogeneous phase reactions in composition of human body fluid, with various ion
aqueous at elevated temperature (T > 25C) and concentrations nearly similar to the inorganic
pressure (P > 100 kPa) to crystallize ceramic materials constituent of human blood plasma. The ion
directly from solutions36. However, with the concentrations of SBF solution is given in Table 1.
hydrothermal treatment, the Ca/P ratio for the Metastable SBF has been proven to generate the
precipitates improves with the increase in growth of carbonated and bone-mimetic apatite on
hydrothermal pressure or temperature37. various orthopaedic and dental biomaterials like silica,
Manafi et al19 synthesized HAp by dissolving titania, bioglass etc at physiological pH and
CaHPO4. 2H2O/NaOH/distilled water, followed by temperature38-40. The formation of apatite layer by this
adding 2-3 gm cetyl trimethyl ammonium bromide biomimetic deposition process on several orthopaedic
(CTAB). The hydrothermal synthesis was conducted at and dental biomaterials was proven to promote in vitro
150C for 2 hours in an electric oven. cell differentiation in mineralized chondrocyte cell
culture system41 and induce osteogenic cell
Multiple emulsion technique: differentiation with subsequent bone-matrix
Kimura20 developed an alternative approaches apposition, which allows a strong bonding with bone42.
for HAp synthesis by interfacial reaction in a multiple Using this method, various porous implants
emulsion. The multiple emulsion was a w/o/w can be coated with nanosized carbonated HAp
emulsion, made of dipotassium hydrogen phosphate biomimmetically by immerging implants in SBF43.
[K2HPO4] solution as an inner aqueous phase, benzene The nature of the HAp coating, via its microstructure,
as an oil phase, and Ca(NO3)2. 4H2O as an outer its dissolution rate and its specific interactions with
aqueous phase. The interfacial reaction was carried out body fluids, can influence the osteogenecity of the
at 323 K for 24 hours. The crystalline phase was varied coating as well as the bone remodeling process.
with an initial pH of the inner aqueous phase, and a
single HAp was synthesized at an initial pH of 12. The Electrodeposition technique:
synthesized products were composed of porous Ultrafine-grained, nanophase HAp coating can
microspheres of less than 3 m in size. This method be synthesized by electrodeposition from dilute
has some advantages20. A common stirred tank is electrolytes [Ca2+] = 6.1 X 10-4 M, [PO43-] = 3.6 X 10-4
sufficient to be used as reactor, and therefore, any M at physiological pH23. The precursors used for the
special apparatus is unnecessary. Low synthesis electrodeposition of HAp coatings were Ca(NO3)2 and
temperature around room temperature are usable. NH4H2PO4. Sodium nitrate NaNO3 was used to
improve the electrolytes ionic strength. Manso et al44
Biomimetic deposition technique: investigated the growth of HAp coating induced by
Metastable synthetic body fluid (SBF) with an constant anodic voltages (2-4 V) in an alkaline
organic salt composition similar to that of human body electrolyte.
fluid (blood plasma), facilitate the spontaneous
nucleation and growth of nanosized, carbonated and CONCLUSION
bone-mimic HAp at physiological pH and It can be concluded that HAp can be
temperature. Thamaraiselvi et al22 synthesized synthesized by various methods like precipitation
biomimetic HAp from Ca(NO3)2. 4H2O and technique, sol-gel approach, hydrothermal technique,
(NH4)2.HPO4, dissolved in SBF at 37C. multiple emulsion technique, biomimetic deposition
Amit Kumar Nayak /Int.J. ChemTech Res.2010,2(2) 906
technique, electrodeposition technique etc. Scientists applications. We expect that, with continuous research
and researchers are engaged in solving various efforts they will develop various novel and economic
challenges related with synthesis HAp with optimum synthesis methodologies of HAp for the near future.
properties for the use in various biomedical
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