COUCHES COMPOSITES DE PHOSPHATE DE CALCIUM BIOACTIVES DEPOSEES ELECTROCHIMIQUEMENT SUR DES IMPLANTS

BIOACTIVE CALCIUM PHOSPHATE COMPOSITE LAYERS ELECTROCHEMICALLY DEPOSITED ON IMPLANTS

Abrégé français

L'invention concerne des couches composites de phosphate de calcium bioactives déposées électrochimiquement sur des implants osseux. De tels implants sont implantés sans ciment et se caractérisent par un pouvoir d'ostéointégration amélioré. Lesdites couches composites ultra-poreuses destinées à des implants sont composées d'au moins deux phases de phosphate de calcium de solubilités différentes. La structure ultra-poreuse de ces couches permet de simplifier l'immobilisation de cellules à partir desquelles le tissu osseux peut se régénérer. Les solubilités différentes des composantes de couches individuelles permettent d'obtenir la concentration locale d'ions calcium et d'ions phosphate accélérant le processus de guérison et s'adaptant au processus dans le temps.

Abrégé anglais

The invention relates to calcium phosphate composite layers which are
electrochemically deposited on bone implants. Implants which are coated in
such a way are implanted without cement and are characterised by improved
growing-in behaviour. Said highly porous composite layers on implants are made
of at least two calcium phosphate phases of different solubility. The highly
porous structure of said layers facilitates the immobilisation of cells from
which new bone tissue can be made. The different solubility of the individual
layer components ensures local concentration of calcium and phosphate ions
which accelerates the incorporation process and which adapts to said process
over the course of time.

Revendications

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CLAIMS
1. A bone implant comprising:
an implant body; and
an electrochemically separated, bioactive, calcium-phosphate composite
layer on said implant body, said composite layer being absorbable in use and
comprising calcium-phosphate phases of relatively high solubility in body
fluids to which said implant will be exposed in use and calcium-phosphate
phases of lower solubility in said body fluids,
wherein said composite layer has a microporous structure,
wherein said calcium-phosphate phases of relatively high solubility comprise
monetite and/or brushite and
wherein said calcium-phosphate phases of lower solubility comprise
hydroxyapatite.
2. A bone implant according to claim 1, wherein said composite layer is
completely dissolved and substituted by new bone in use.
3. A bone implant according to any one of claims 1 to 2, wherein said
composite
layer further comprises osteoinductive additives.

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4. A bone implant according to any one of claims 1 to 3 wherein said composite
layer further comprises antimicrobial agents.
5. A process for producing a bone implant, said process comprising the deposit
of calcium- phosphate phases of relatively high solubility in body fluids to
which said implant will be exposed in use on an implant body and partially
converting same to calcium-phosphate phases of lower solubility body fluids
to which said implant will be exposed in use to produce an electrochemically
separated, bioactive calcium-phosphate layer on said bone implant body,
said layer having a microporous structure, said calcium-phosphate phases of
relatively high solubility in body fluids comprising monetite and/or brushite
and said calcium-phosphate phases of lower solubility in body fluids
comprising hydroxyapatite.

Description

CA 02416201 2003-07-23
WO 02/05862 PCT/EPOO/06838
BIOACTIVE CALCIUM PHOSPHATE COMPOSITE LAYERS ELECTROCHEMICALLY
DEPOSITED ON IMPLANTS
For about 10 years investi.gations on c;alc::.iLir phosphate layers
electrochemically deposited ori k~,anr~~ im.pl,!:rnts have been carried
out with the objective to improve the compound between the bone
tissue and implant (Redepenning, J. et aL.: Chem. Mater.
2(1990) 625-7; Redepenning, J.G.: US 5, 3]..0, 464, US 5, 413, 693;
Teller, J. et al. :]aE 4 431 862, EP 774 ')82, US 5, 759, 3"76;.
Kumar, M. et al.: J. Fiiomed. Mat. Res. 4!::; t 1.999 ) 302-10) ,
Calcium phosphates as miner.a:l. c.onst:..it.uerlt:s of the bone tissue
have bioactive properties, ie. they assist the bone formation.
The genesis of calcium phosphate layers trom electrolytic baths
deposited on implants are ve.ry simi.lar t::,o the processes
proceeding during the bone cfrowt.:lr. 'I't-iei;_ r=,i..cr_oporous structure
encourages the immobi.lizat--.ion of ce_L1s,, whi.crl leads to :caew bone
tissue being allowed to forn ar~Gd to k,n_i :. together with the bone
tissue surrounditZg the implant such as with normal wound
healing.
In the literature, besides the preparatiari of phase-pur.e
calcium phosphates it. is also known to h.ave composite layers
electrochemically deposited on irnpiants. US :'atent 5, 20'>, 921
(Shirkhanzadeh, M.) and DE Patent 4, 43:1., 862 ;7:'eller, J. et.
al.) describe the electrochemical nepostt.l_on of calc.ium
phosphate composite layers from t:.r (:.ait.iuiTl prioUphate and
Y Y p from more :(-.ralf. a~.~1u~ible c~al~,iun;
h drox la atite ftwo mo.rE, dii'!"':E. ~
phosphate phases. DE 19 504 386 (Scharnweuer, D. et_ al.) deals
with an electrochenlical method fcx~ the preparation of a refined
adhesive-proof coating from Ual.ci.um pnosphat.e and metal oxide
phases on titanium implants by a mutua;l cathodic and anodic

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polarization. Another method for the preparation of adhesive-
proof hydroxylapatite/cobalt composites uses electrochemically
deposited brushite layers which are chemically convertESd into
hydroxylapatite ard are subsequent-1y c_:oat:ed with cobalt: in
another bath (Zhar:,g J.M. et. al.. J. Mat. ;>>c;i.. Lett. 11 (1998)
1077-9) . With the difficult so.l.cable calcium phosphate phases,
in particular hydroxylapat.ite, one seeks by the preparation of
these composite layexs to achieve a possibly great, similarity
to the structure of natural fuL1 developc.,d bone, and this will
encourage the implant to be het.lc,:!d int:c) i::he b~:)ne. It can be
assumed that due to its low so:i_:ibil:it.y the hyd.r.(:)xylapatite
remains on the implant, and thus a ciurab:l_e improvement of the
interaction between the implant surtace arid biological system
will be achieved. Also, attempLs to compLetely convert brushite
layers electrochemically depos,ited orr irti}->.lants into
hy(droxylapatite are made with the ok).,jecr.ive to arti.ficially
develop bone similiar rel.at.:.c:>n:-, cri the ir ipl.ant::, forever.
Although the body thus is offered :a sur_t;~~~~ace known to it, such
layers have a disadvantage in Lhat due to their low solubility
they only excite the bone moderatei.y for the endogenous
osteosynthesis.
From the literature it has been known for several years that
the grade of bioactivity of a:layer grows with its instability
in a physiological ambiance. Good conditions for the
reproduction and differentiation of the osteoblasts responsible
for bone formation are provideci by a local L'lcrease of ':-he
concentration of calci_um and ph,'-3slahaC:.e i.ars Ln the hea:1_;ing zorle
of the implant. (Ducheyne, P. 1i:ioma:verials 11(1990)
531-40) . Calcium phosphates with a so.luatdli.r-y very mucl-I higher
than that of brushite and monet.i.te in corr:parison with
hydroxylapatite thus have a paz_.icular importance, especially
for the healing phase of the implant ;irct.c the bone.

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Hence, the present invention seeks to deposa.t a layer on the
bone implant which optimally assists heali.ng the implant into
the bone, which then wi li be eritirc:ly resorbed and thus enables
the immediate and complet.e frict.:i.on--fit contact of the bone
with the i.mplant.
According to the inventiori, a bone irnplant (.~omprises an i_mplant
body and an electrochemicaliy se=j~:)a:rated, bicoact.:ivE~~, calcium-
phosphate composition layE,,r on t.}ze i.rnpl.arit k.~)ody, the composite
layer being fully absorbable an(i comprises i:reely soluble
calcium-phosphate phases of young bone 'vissue and less soluble
calcium-phosphate phases of mo.,_e developt~d x;,one, wherein the
composite layer has a mi.cropor,:)_a:.,
The composite layer according to the invention especially
includes the more easily solubie phases of the young bone
tissue in addition to the more di.ff icõult c~;oluab:Le calcium
phosphate phaes of the more developed b~.:)ne. Tn particuar, the
easily soluble phases of brushi_te and monetite are allowed to
actively assist the endogenous osteUgene:ais by locally
increased calcium and phosj,:>hat_ c7 c f=r,r t t,icn:> since the
reproduction and matur.ati,Dn of osteobla:at:.cs required for the
osteogenesis is accelerated under these condit;.ons. After the
dissolution of the more easily soluble p},ases has taken place
the more difficult soluble phases erisure a s:Liyhtly increased
concentration of calcium and pl tosphat.e :i.c,ns Over a longer time
period in the healing zone of the -impl.arit, thus encouraging the
enlargement and st3biLization of the new bone tissue.
Due to the high-porous st.ructuz:'(~ aci.justak;~l.e by t:he pararnet.ers
of the electrochem.icai. depos:i_t.:ic3n, the corrpos:i.t:e layer is not
allowed to serve and does not serve as a barrier betwee:i the
implant and bone. However, the coiTrposi.tr~ l.ayer serves as a
harmonizing factor or host with e.ndc~genous structuring ~.:)f the
boundary layer between the imp:i.ara.k: and b(:)rie. 'i'he high

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bioactivity of this spongy comi;, .itF inani.te: ts, ;itsel.f iii
excellent moistening due to the body f1,iid F.,re.sent in the wound
bed of the bone and the adhesi<:;n c.r)nnc~c.~~r,<:i therewith due to the
contents of this fluid, and in st.i.rculati.nq the ost.eogenesis.
The composite layers c:an be adapted tU zespect:ive irnplant
and the bone surrounding the i.crtplant wi.th xe.spect to the
structure, compositiori and t:hickne.;s.
The preparation of this composite is carried out so that the
individual phases are simuitanF-~oi.~,sly or ~uk:,sequent::ly deposited
as well, the portions of orie pPaaFe, e.g of the more soi_uble
calcium phosphate phase, respe~~tivel.y ar~, ccnvF_ rted into a less
soluble phase by means of a c:.herrr.ica.l re.ak:t::i.on. With this
method, superficially i_t is ro': :interided provide a v,~rtical
solubility gradient i.n the composi_t:e. ln.>tead, the different
phases laterally develop side t,y side and di s_-.olve agair after
iplantation. Then, the porosity of the composite first will
increase due to the decrease ot- the more easi:ly soluble phases,
and this will make room for new borie tissue until the entire
composite is converted into borie tissue after dissolving the
less soluble calcium phosphate phases. from first
coritacts of the immobilized cel1.:: with irrrpl.ant via the
pores of the compos.ite, a c,:nnncct ion between the
bone and implant deve7_ops rz--om 1:1;e k>egi rirl i_r.q by tlie proc.eeding
dissolution of the :i.ndivi.dua1. phases.
The time history of ttie dissoli..at::iori. of the composite layer_ can
be simply characerized by thref:-~ phases. Izl phase I, the
greatest local increase of t:t- e concentraÃ.::i.on o:t: calcium and
phosphate ions available in the boundary Layer between the
implant and bone is s;.zbstant.i.a:L:l_y :.:!etc.:r:rni.ned by the more easily
soLuble phases. In this section it must ;:>c, ensured that a
fibrous encapsulation of the implant dcc=;-~ r,c t: ~::ac::cur, thus
enablirig its immediate oster>~~ni.~ gra.t...ion, 1:n phase II th~> more

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difficult soluble compsite po t:ion wi:L~l. determine the local ion
budget, and in paritcular will assist the mineralization of the
new bone tissue. In phase III t.i-ie ent::i.z--c-'. composite is (lissolved
and substituted by a new l,-)orre.. '['he implc,r-st. Ls healed :i.r:to thE?
bone in a frictiorl-fit manner.
In case of need, osteoinductive additives and/or antim1.crobial
agents carl also be released frorn the c:;ompos:t e.
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