Comprehensive Review of Preparation Methodologies of Nano Hydroxyapatite
P. Anitha1, Haresh M. Pandya2*
1
2
PG Department of Physics, Vellalar College for Women, Erode, India.
Department of Physics, Chikkanna Government Arts College, Tirupur, India.
*Corresponding author: haresh.pandya@rediffmail.com
Abstract
The present paper provides a snapshot review of nano hydroxyapatite (HAP), its importance in biomedical and
orthopedic fields and its various preparation methodologies. Most recent research related to these preparation
methods are also reviewed comprehensively.
Key words: Hydroxyapatite, sol gel, hydrothermal, microwave, ultrasonic, mechanochemical
1 Introduction
I t is a we l l -e st ab l is h ed fac t t ha t t he H u ma n
b o ne co n si s t s o f 2 0 % o f co l le ge n fib r i ls, 6 9 %
o f na no s ize cr ys t al li n e i no r ga n ic p ha se a nd
9 % o f wa ter ( Mo l laz ad e h et a l.2 0 0 7 ; N ej ali et
al) T he s e Na no s ized cr ys tal li n e co mp o si te
in g red i e nt s ma i nl y r e s e mb le h yd r o x ya p a tit e
( H AP ) – Ca 1 0 ( P O 4 ) 2 ( OH ) 2 b as ica ll y a t yp e o f
calc i u m
p ho sp ha te,
wit h
s tr uct u ral
d i me n sio n s s i mi lar to a r o d o r a need l e
( le n gt h
4 0 -6 0 n m,
wid t h
1 0 -2 0 n m
a nd
th ic k n es s 1 - 3 n m) ( Lu i s C Me nd e s et al.
2 0 1 2 ). F urt h er, i t is a l s o co n sid er ed a s o ne o f
th e mo s t si g n i fic a nt h u ma n i mp l a ntab le
ma ter ia l s o n t h e b a s is o f t he d e gr e e o f it s
b io co mp a tib il it y,
b io ac ti v i t y
a nd
Os tero co nd uct i vi t y ( Al es sa nd r a B ia nco e t
al.2 0 0 7 ) . I n ad d it io n, it s a f f i n it y to crea te
q ui c k b o nd s wi t h ne i g h b o r i n g b o ne s ma k es i t
al so a d e si g n er ma te r i al fo r b o ne r ep a ir o r
ar ti fic ia l b o ne s ub st it ut e. T h e c he mic al,
str u ct ur al a nd mo r p ho l o gi ca l p r o p er tie s o f
H AP b io c era mi c ar e hi g h l y se n s it i ve to
ch a n ge i n p h ys i ca l p r o p er ti e s, c he mi c al
co mp o s it io n a nd p r o ce s s in g te mp er a t ur e.
J in g B i n g Li u et al . 2 0 0 3 ; De l i a e t a l.
2 0 1 2 ; Me h maz Sa lar ia n et a l. 2 0 0 8 )
(ii i)
Ult ra so nic
As s is ted
I rrad ia tio n
Met ho d ( Sa heb al i M a n afi et al. 2 0 0 8 ;
Gera nd Ed d y P io neer et al . 2 0 0 9 ;
Ko j i ma e t a l. 2 0 1 2 ; E n y K us i ni et al.
2 0 1 2 ; Co a L i Y u n et al . 2 0 0 5 )
(i v)
Mec ha no
C he mi ca l
M et ho d
( T o mo h iro I wa sa k i e t al . 2 0 1 1 ; Ad z ila
et a l. 2 0 1 1 ; Rad zal i Ot h ma n e t a l;
Yeo n g e t a l 2 0 0 1 ; Gret a Ger ge l y e t al .
2010)
(v)
Micro wa v e I rrad i at io n Met ho d ( Go b i
et a l. 2 0 1 3 ; Sid d ha rt ha n e t al . 2 0 0 5 ;
Sa h il J a lo ta et al. 2 0 0 4 ; Mo ha m ma d
B hi la l K ha n e t a l. 2 0 1 1 ; Sa ma r kal it a
et a l. 2 0 1 0 ) a nd
(v i)
So l G e l me t ho d ( Ald o n a et al . 2 0 0 6 ;
An b al a ga n et a l. 2 0 0 6 ; Sa nto s h et al .
2 0 0 9 ; C h a n gs h e n g Li u et al . 2 0 0 1 ;
K hel e nd ra Ag ar wa l et a l . 2 0 1 1 ) .
A re vi e w o n mo s t rec e nt wo r k d o ne i n t h es e
me t ho d s i s p ro v id ed b el o w.
2 Nano Hydroxyapatite Preparation Methods
Sci e nt i fi c l iter at ur e fi n d s me n tio n o f se ver al
me t ho d s o f p r ep ar a tio n o f Na no H AP . T he
mo st freq u e nt l y u sed me t ho d s a mo n g t h e se
ar e
( i)
( ii)
Co -P rec ip i ta tio n
Met ho d
( Zh a n g et al. 2 0 0 3 ; Da n N ico lae
U n g urea n u a t al. 2 0 1 1 ; J ainp i n g Zh u
et al 2 0 1 1 ; Lui s C Me nt es et a l. 2 0 1 2 ;
Ro z it a Ah ma d Ra mi l et al. 2 0 1 1 )
H yd ro t he r mal
M et ho d
( Na s ser
Y
Mu s ta fa e t al. 2 0 1 1 ; Ea r l et al . 2 0 0 6 ;
2.1 Co-Precipitation Method
T hi s i s t he o n e o f t he mo st wid el y ad o p ted
me t ho d s
d ue
to
it s
s i mp l ici t y,
r ap id
p rep ara tio n as we ll as e as y co ntro l o f p ar ti cle
si ze, co mp o s it io n a nd v ario u s p o s sib il it ie s to
mo d i fy o vera ll ho mo g e ne it y o f t he p ro d uc t.
T he fir st st a ge co n si st o f mi x i n g t he An io n
so l u tio n e . g. ca lc i u m so urce wi t h C at io n
so l u tio n e . g. p ho sp ho ro u s so l ut io n fo l lo we d
b y fo r ma tio n o f n uc le at io n , p r ecip it at io n a nd
fil trat io n. T he fi na l sta g e co ns i st s o f
calc i na tio n s u nd er d e si r ed te mp er at ur e (Fi g
1).
T ab le 1 s ho ws th e r ece n t r e vi e w o f
p ap er s re la ted to Co -P r ecip ita tio n me t ho d i n
th e la s t t wo d ecad es i n th i s met ho d . D ue to
th e si mu l t a neo u s o cc u r r e nce o f n u cl eat io n
and cr ys t a l gro wt h, t he re ac tio n i n t h i s
me t ho d r eq uir e s a s harp fi n e t u ni n g to
o p ti mi ze mo rp ho lo g y and mi n i ma l c r ys ta l
gro wt h.
Table 1: Co Precipitation Method
2.2 Hydrothermal Method
T hi s me t ho d i n vo l v es t h e u sa ge o f wat er as a
so l v e nt h eat ed i n a se aled v es s el. T ab l e 2
s ho ws t he rec e nt r e vi e w o f p ap er s r e la ted to
th e h yd ro t her ma l me t ho d
T he i n it ia l s ta g e i n t h e s yn t h e si s o f Na no
H AP i n t h i s me t ho d is cho o s i n g t h e Ca lc i u m
and P ho sp ho r o u s p r e cur so r fo llo wed b y
mi x i n g t he t wo b y ma i n tai n i n g t he Ca /P ra tio
at
a
co n st a nt
va l u e
of
1 .6 7
u nd e r
h yd ro t her ma l r eac to r m ec ha ni s m ( F i g 6 ) . T he
mi x i n g i s t he n al l o wed to a g e , a nd
s ub seq ue n tl y wa s h ed a nd f il ter ed . Fi n al l y it
is d ri ed i n a n o ve n a nd calc i ned us i n g mu ffle
f ur n ace. T ab l e 2 s h o ws t he r e vie w o f
h yd ro t her ma l me t ho d wo r k d o n e i n t h e la s t
t wo d ecad e s .
T he c ha n g e i n t he s o lv e nt a nd r e act a nt
p r o p erti e s a t a n e x tr e me t e mp er at ur e me a ns
th at e xp er i me n tal v ar i a b le s ca n b e co nt r o ll ed
to a h i g her d e gr e e i n t h is me t ho d . T h is
r eg u la te s t h e cr ys t al .
Table 2: Hydrothermal Method
2.3 Ultrasonic Irradiation Method
T hi s
me t ho d p ro d uc e s
na no
H AP
by
irrad i at i n g t h e mi x t ure o f Ca So urc e a nd P
(Fi g 1 1 ) wi t h a s o urce o f ul tra so n ic rad ia tio n
o f var yi n g fr eq ue nc ie s a nd p o wer . T he
o b tai n ed mi xt u re i s a wel l -d e fi ned p ro d uct
wi t h hi g h p ur it y. T ab le 3 hi g h li g h t s t he
rece n t re v ie w o f p ap ers rel at ed to t h i s
me t ho d . P h ys i ca l a nd c he mi c al p ro p er tie s o f
th e o b t ai ned mi x t u re ha v e b e e n fo u nd to
ch a n ge wi t h vari at io n in freq ue n c y a nd
p o wer .
Mi xi n g Ca a nd P p rec ur so r, ma i nta i ni n g Ca /P
ratio a nd p H a s a co n st an t val u e i s t he fir st
and fo re mo st step i n t he s yn t h e si s o f N a no
H AP b y t hi s met ho d fo l lo wed b y t he p a s sa g e
o f u ltr a so nic wa v e s o f d es ired fr eq ue nc y a nd
p o wer fo r a sp e ci fic irr ad ia tio n t i me. D r yi n g
and ca lc i nat io n s ar e fo llo wed b y u ltr a so nic
trea t me n t. T ab l e 3 s ho ws t h e re v ie w o f
ul tra so n ic irrad ia t io n m et ho d wo r k d o ne fro m
2003
to
2012.
Table 3: Ultra sonic irradiation method
2.4 Mechano Chemical Method
T he Mec h a no C h e mi cal me t ho d i s t he
co mb i na tio n o f mec h an ica l a nd c he mi ca l
p he no me n a o n a n a no sca le so l id ma ter ia l.
Here na no ma te r ia l s ar e s yn t h e siz ed b y
me c ha n ica l a ct i va tio n and i n t h is me t ho d ,
b all mi l li n g i s a wi d el y u sed t ec h niq u e
wh ere i n t h e p o wd er mi xt u r e is p la ced i n a
b all mi ll a nd i s s ub j ected to h i g h e n er g y
co ll i sio n fro m t he b al l s and t h u s me c ha n ica l
fo r ce i s u sed to ac hi e v e ch e mi cal p r o c e ss i n g
and tra n s fo r ma tio n . Co nt a mi n at io n, lo n g
p r o ce ss i n g t i me, no co n tr o l o n p ar t ic le
mo rp ho lo g y, a g glo mer ate s, a nd r e s id ual
str ai n i n t h e cr ys ta ll ize d p ha se ar e t h e o t her
d is ad va nt a ge s o f h i g h -e n er g y b al l mi ll i n g
p r o ce ss. Ho we v er , t he me t ho d i s fa mo us fo r
it s re s ul ts , va rio u s ap p l ica tio n s a nd p o te n ti a l
sc ie nt i fi c va l ue s. T ab le 4 s ho ws t h e r ec e nt
r ev ie w o f p ap er s r e lat e d to na no H AP wi t h
Mec ha no C he mi ca l me t h o d
T he met ho d co ns i st s ma in l y o f m i x i n g Ca a nd
P , mai n tai n i n g Ca /P r a tio a nd p H ( F i g 1 6 ) .
T he h i g hl i g ht o f t hi s me t ho d i s c ho o s i n g a
me c ha n ica l mi ll i n g wit h s el ect ed mi ll i n g
med ia s uc h a s Zir co ni a, a ga te, a l u mi n a,
st ai n le ss s tee l e tc. wi t h p arti c ul ar sp eed a nd
d ura tio n as wel l a s cr it i cal l y m ai n ta i ni n g t he
b all ma s s ra tio . T h e s a mp le s are g i ve n hea t
trea t me n t. T ab l e 4 s ho ws t h e re v ie w o f
Mec ha no C he mi ca l me t ho d wo r k d o n e i n t he
la st t wo d ecad es .
2.5 Microwave Assisted Irradiation Method
T hi s met ho d is o n e o f th e ad va nc ed
me t ho d s fo r t he p rep a ratio n o f na no H AP
wi t h a n as so c ia ted d i sad va n ta g e t ha t t he
p ro ced ure i s e x te nd ed in co mp ari s o n wi t h
o th er
me t ho d s .
Mi cro wa v e
irrad ia tio n
p ro v id e s
an
e ffi cie nt ,
e n v iro n me n tal l y
fr ie nd l y a nd eco no mic a ll y vi ab l e me t ho d o f
he at i n g d ue to i ts i nc re ased rea ct io n ki ne ti c s
and rap id i n it ia l he at i n g co up led wi t h red uc ed
reac tio n
ti me s
wh en
co mp ar ed
to
co n v e nt io nal
hea ti n g
met ho d s
fi na ll y
cu l mi n at i n g i n p ro d uc ts in p o wd er fo r m t h at
are we l l d e fi ned , o f h i g h p ur it y a nd
ho mo ge n eo u s . T ab le 5 s ho ws t he r ece n t
rev ie w o f p ap er s re lat ed to mi cro wa v e
as si s ted irrad iat io n me t h o d .
T he u s ua l s tep s o f mi x i n g Ca+P , ma i nta i ni n g
Ca /P rat io a nd p H ar e all fo llo wed . T he
seco nd s tep to b e fo llo wed is p a ss i n g
mi cro wa ve r ad ia tio n fo r a sp eci fic ti me
fo llo wed b y he at t rea t m en t ( Fi g 2 1 ) . T ab l e 5
rev ie ws wo r k d o ne i n t hi s me t ho d i n t he l as t
2 0 year s.
Table 5: Microwave Assisted Irradiation Method
2.6 Sol Gel Method
T he So l Ge l me t ho d ha s o f la te at tr a cte d
d ed ica ted
at te nt io n b y a
maj o r it y o f
r es earc h ers d u e to i ts ma n y sp e ci al fe at ure s
s uc h as lo w te mp er a t u r e gr o wt h , lo w co s t ,
ho mo ge n eo u s mo l ec ul a r p r o d uc t s a nd t h e
ab il it y to p ro d uce na no siz ed p ar t ic le s ea s il y
wh e n co mp ar e d wi t h o t her me t ho d s . T ab le 6
s ho ws t he rec e nt r e vi e w o f p ap er s r e la ted to
So l g el me t ho d
T he fir st s tep to b e fo llo wed i n so l g el
me t ho d i s t he c ho o si n g a Ca p r e c ur so r a nd
P ho sp ho r p rec ur so r ( Fi g 2 6 ) .T h e s eco nd s tep
is mi x i n g t h e ab o ve a n d f i xi n g t he p H wi t h
a m mo nia o r a m mo n i u m h yd r o xid e, fo llo wed
b y a gei n g, fi ltr at io n, d r yi n g a nd c al ci na tio n s.
T ab le 6 s ho ws t he r e vi e w o f so l ge l me t ho d
wo r k d o ne i n t h e l a st 2 0 ye ar s .
.
Table 6: Sol Gel Method
3 CONCLUSION
In t he p r e se nt r e sear c h ar ti cl e si x d i ffer e nt
me t ho d s fo r t he p r ep ar atio n o f na no H AP
ha v e b e e n d e sc r ib ed a nd t he la te st r e se arc h
in t ho se me t ho d s i n t h e la s t t wo d ecad e s
ha v e a lso b ee n r e v i e wed .
O f t he met ho d s l is ted ab o ve wi t h t he ir
var yi n g met ho d o lo gi e s, the a u t ho r s feel
th at t h e so l g el me t ho d is t h e s i mp l es t a nd
eas ie st o f t he d e scr ib ed me t ho d s to
p ro d uc e hi g h p ur it y, ho mo ge n eo u s na no
H AP fo r s ub seq u e nt u s ag e i n b io me d ic al
and o rt ho p ed ic ap p l ica ti o n s.
Reference:
Adzila, S., Sopyan, I., and Hamdi, M., Synthesis of
Hydroxyapatite
through
Dry
Mechanochemical Method and Its Conversion
to Dense Bodies: Preliminary Result, IFMBE
Proceedings, 35, 97–101(2011).
Doi.org/10.1007/978-3-642-21729-6_27
Aldona Beganskiene. Irma Bogdanoviciene and
Aivaras Kareiva., Calcium acetylacetonate- a
novel calcium precursor for sol - gel
preparation of Ca10(PO4)6(OH)2, Chemija,
17(2-3), 16-20(2006).
Alessandra Bianco., Ilaria Cacciotti., Mariangela
Lombardi., Laura Montanaro and Gusmano,
G., Thermal stability and sintering Behaviour
of Hydroxyapatite Nano powder, Journal of
thermal Analysis and calorimetry, 88(1), 237243(2007).
Doi: 10.1007/s10973-006-8011-6
Anbalagan Balamurugan., Jean Michel., synthesis
and Structural analysis of Sol gel derived
Stoichiometric Monophasic Hydroxyapatite,
Ceramic, 50(1), 27-31(2006).
Changsheng Liu, Yue Huang, Wel Shen, Jinghua
Cui, Kinetics of hydroxyapatite precipitation at
pH 10 to 11, Biomaterials, 22, 301-306(2001).
doi.org/10.1016/S0142-9612 (00)00166-6
Coa Li Yun., Zhang Chuan Bo., Huang Jianteng.,
Influence of temperature, [Ca2+], Ca/P ratio
and ultrasonic power on the crystallinity and
morphology of hydroxyapatite nanoparticles
prepared with a novel ultrasonic precipitation
method, Materials letters, 59(14-15), 19021906(2005).
Doi: 10.1016/j.matlet.2005.02.007
Dan Nicolae Ungureanu., Nicolae Angelescu., Zorica
Bacinschi., Elena Valentina Stoian., Cristiana
Zizi Rizescu., Thermal stability of chemically
precipitated hydroxyapatite Nano powders,
International Journal of Biology and
Biomedical Engineering., 5(2), ( 2011).
Doi: 978-960-474-276-9
Delia, N.L., Gavina, A.W., and Messina, P.V.,
Synthesis
and
Characterization
of
hydroxyapatite Nano rod with potential
biomedical Application, Mab IV.
Earl, J.S., Wood, D.S., and Milne, S.J., Hydrothermal
synthesis of hydroxyapatite, Journal of
Physics: Conference Series., 26, 268–
271(2006).
Doi: 10.1088/1742-6596/26/1/064
Eny Kusrini., Aida R. Pudjiastuti., Sotya.
Astutiningsih. and Sri. Harjanto., Preparation
of Hydroxyapatite from Bovine Bone by
Combination Methods of Ultrasonic and Spray
Drying.,
International Conference on
Chemical, Bio-Chemical and Environmental
Sciences, 14-15, (2012).
Gerard Eddy Pioneer., Ravi Krishna Brundavanam.,
Nicholas Mondinos, Zhong Tao Jiang,
Synthesis and Characterization of Nano
hydroxyapatite using an ultrasound assisted
method, Ultrasonic Sonochemistry,16(4), 469474(2009).
Doi.org/10.1016/j.ultsonnch.2009.01.007
Gobi, D., Indira, J., Nithiya, S., Kavitha, L., Kmchi
Mudali, U., and Kanimozhi, K., Influence of
surfactant
concentration
on
nano
hydroxyapatite growth, Bull. Mater. Sci.,
36(5), 799–805(2013).
Doi: 10.1007/s12034-013-0540-6
Gréta Gergely., Ferenc Wéber., István Lukács.,
Levente Illés., Attila L. Tóth., Zsolt E.
Horvath, Judit Mihály., Csaba Balázsi., Nano
hydroxyapatite preparation from biogenic raw
materials, Cant. European
Journal of
Chemistry, 8(2)., 375-381.
Doi: 10.2478/s11532-010-0004-4
Jianping Zhu., Yin Zhang., Nengjian Yao., Yaqiu
Tao and Tai Qiu., The Influence of Conditions
on Synthesis Hydroxyapatite By Chemical
Precipitation Method, Materials Science and
Engineering., 18 (2011).
doi:10.1088/1757-899X/18/6/062023
Jing Bing Liu, Xiaoyur Ye, HaoWang, Mankang
Zhu, BO Wang, Hui Yan, The influence of pH
and temperature on the morphology of
hydroxyapatite synthesized by hydrothermal
method, Ceramic International., 29(6)., 629633(2003).
Doi.org/10.1016/S0272-8842 (02)00210-9
Khelendra Agarwal, Gurubhinder Sing, Devandra
Puri,
Satya
Prakash,
synthesis
of
hydroxyapatite powder by sol– gel method
for biomedical application Journal of
materials and material characterization and
Engineering, 10(8), 727-734
Kojima, Y., Kitazawa. K and Nishimiya, N.,
Synthesis of Nano-sized hydroxyapatite by
ultrasound irradiation, Journal of Physics:
Conference Series, 339(1), (20112).
Doi: 10.1088/1742-6596/339/1/012001
Luis C. Mendes., Geysy L. Ribeiro., Raphaella C.
Marques., In Situ Hydroxyapatite Synthesis:
Influence of Collagen on Its Structural and
Morphological
Characteristic,
Materials
Sciences and Applications, 3, 580-586 (2012).
doi:10.4236/msa.2012.38083
Mehmaz Salarian., Mehran Solati Hashjin., Azadeh
Govdarzi., Effect of Surfactant in formation of
hydroxyapatite Nano rods under hydrothermal
Condition., Iranian Journal of Pharmaceutical
Sciences., 4(2), 157-162(2008).
Mohammad Bilal Khan, Rafaqat Hussaun,
Mohammad Aftab Akram, Nida Iqbal,
Structural and thermal stability of microwave
synthesized
nano
hydroxyapatite
Supplementary proceeding, 3, TMS, 2011.
doi.org/10.1002/9781118062173.ch45
Mollazadeh, S., Javadpour, J., Khavandi, A., In Situ
Synthesis and characterization of Nano size
hydroxyapatite in poly (vinyl alcohol) matrix,
Ceramics International, 33, 1579-1583 (2007).
Doi: 10.1016/j.ceramint.2006.06.006
Nasser Y. Mostafa.,
Characterization, thermal
stability and sintering of hydroxyapatite
powders prepared by different routes.,
Materials Chemistry and Physics., 94, 333–
341(2005).
Doi.org/10/1016/j.matchemphys.2005.05.0114
Nejati, E., Firouzdor, V., Eslaminejad, M.B., and
Bagheri,
F.,
Needle
like
Nano
hydroxyapatite/poly (l-lactide acid) composite
scaffold for bone tissue engineering
application.
Materials
Science
and
Engineering: C, 29(3), 942–949(2009).
Doi.org/10.1016/j.msec.2008.07.038
Radzali Othman.., Azlila Zakaria, Optimization of
Milling Parameters during mechanical
Activation
for
Direct
Synthesis
of
Hydroxyapatite. ASEAN Engineering Journal,
1(4), 5-11(2011).
Rozita Ahmad Ramli., Rohana Adnan., Mohammad
Abu Bakar and Sam’an Malik Masudi.,
Synthesis and Characterization of Pure Nano
porous Hydroxyapatite., Journal of Physical
Science., 22(1), 20-37 (2011).
Sahebali Manafi., Seyed Hossein Badiee., Effect of
Ultrasonic on Crystallinity of NanoHydroxyapatite via Wet Chemical Method,
Iranian Journal of Pharmaceutical Sciences,
4(2), 163-168(2008).
Sahil Jalota., Cuneyt Tass, A.,and Sarit B Bhaduri,
Microwave assisted synthesis of calcium
phosphate nano whiskers, Journal of Materials
Research., 19(6), 1876-1881(2004).
doi.org/10.1557/JMR.2004.0230
Samar J Kalita. Saurabh Verma., nano crystalline
hydroxyapatite bioceramic using microwave
radiation: synthesis and characterization,
Material Science and Engineering: C, 30(2),
295-303(2010).
doi.org/10.1016/j.msec.2009.11.007
Sanosh. K.P., Min Cheol chu, A.Balakrishnan, T.N
Kim and Seong Jai Cho, Preparation and
characterization of nano hydroxyapatite
powder using sol gel technique, Bull Material
science, 32(5)465-470(2009).
Doi: 10.1007/s12034-009-0069-x
Siddharthan,A., Seshadri, S.K., Sampath Kumar,T.S.,
Influence of microwave power on nanosized
hydroxyapatite particles, Scripta materialia,
55(2), 175-178(2006).
doi.org/10.1016/j.scriptamat.2006.03.044
Tomohiro Iwasaki., Mechanochemical Synthesis of
Magnetite/Hydroxyapatite Nano composites
for Hyperthermia, Material Science, 175194(2013)
Doi: 10.5772/54344
Yeong, K.C.B., Wang, J., Mechanochemical
synthesis of nano crystalline hydroxyapatite
from CaO and CaHPO4. Biomaterials 22,
2705-2712(2001)
doi.org/10.1016/S0142-9612 (00)00257-X
Zhang, S.M., Cui,F.Z., Liao,S.S., Zhu, Han,L.,
Synthesis and Characterization of porous Nano
hydroxyapatite/collagen/ alginate composite,
Journal of Material Science Material in
Medicine, 14, 641-645(2003).
Doi: 10.1023/A: 1024083309982