Biocompatibility of apatite-containing implant materials

Article abstract of DOI:10.1023/A:1004174030633

Thermochemical decomposition of hydroxyapatite in phosphoric acid was studied with the aim of producing polymineral gradient-resorptivity composites. The procedure was tested on the BAK-1000 glass-apatite composite. The results indicate an enhancement of resorptivity, without changes in the performance parameters or crystal structure, thereby suggesting a new approach to controlling the bioactivity of apatite-containing bioceramics.

Full text of DOI:10.1023/A:1004174030633

Inorganic Materials, Vol. 37, No. 2, 2001, pp. 180–183. Translated from Neorganicheskie Materialy, Vol. 37, No. 2, 2001, pp. 233–236.
Original Russian Text Copyright © 2001 by Malysheva, Beletskii.
Biocompatibility of Apatite-Containing Implant Materials
A. Yu. Malysheva and B. I. Beletskii
Mendeleev University of Chemical Technology, Miusskaya pl. 9, Moscow, 125820 Russia
Received November 18, 1999
Abstract—Thermochemical decomposition of hydroxyapatite in phosphoric acid was studied with the aim of
producing polymineral gradient-resorptivity composites. The procedure was tested on the BAK-1000 glass–
apatite composite. The results indicate an enhancement of resorptivity, without changes in the performance
parameters or crystal structure, thereby suggesting a new approach to controlling the bioactivity of apatite-con-
taining bioceramics.
INTRODUCTION
higher than that of HA [8]. The solubility of HA is
immeasurably low in pure water (dissociation constant,
10–100 [9]) but depends strongly on solution pH. The
presence of TCP increases the ionic strength of the
solution, changing the pH and raising the HA solu-
bility.
Materials based on hydroxyapatite (HA),
Ca10(PO4)6(OH)2, are the most widely used inorganic
biomaterials, because HA is closely similar in chemical
composition, structure, and physicochemical properties
to the mineral component of an osseous tissue and pos-
sesses unique biomimetic properties. A major draw-
back of all HA-based materials is their low resorptivity
in physiological solutions with pH 7.3. This is charac-
teristic even for materials prepared at temperatures
below that of the transition to a crystalline condensed
form with a high degree of structural ordering and low
resorptivity.
β-TCP can be introduced in a number of ways;
direct sintering of mechanical mixtures of HA and
β-TCP is not used. In some cases, it is expedient to syn-
thesize HA with the desired β-TCP content by solid-
state reaction. In most instances, however, use is made
of chemical treatment or partial thermal decomposition
of HA. Certain chemical reagents were found to yield
The main lines of research concerned with the prep- granules in which a HA core is sheathed by β-TCP. For
aration of apatite-containing biomaterials with con- example, Berger et al. [10, 11] treated HA with solu-
trolled bioactivity are as follows:
(1) Preparation of nonstoichiometric HA and deter-
mination of its stability conditions;
(2) Modification of the HA structure with foreign
ions;
(3) Design of polymineral composites incorporating
HA and calcium phosphates.
In the first two instances, resorptivity depends on
the structural perfection of HA: nonstoichiometry, type
of solid solutions, site occupancies, and distribution of
the effective charge in the presence of foreign cations.
As for the third line of research, note that the most com-
mon component of composites with HA is tricalcium
β-phosphate (TCP)—the only phosphate which fully
resorbs in human tissue, whereas other phosphates
experience weak resorption and belong to the class of
resistive compounds [1–4]. There is some evidence that
TCP-based implants resorb more rapidly than do HA-
based implants [5, 6]. Jarcho [7] points out that the
resorption rate of implants is proportional to the TCP
content: increasing the fraction of HA reduces the
resorption rate.
tions of phosphoric and sulfuric acids or a mixture of
phosphoric, sulfuric, and hydrofluoric acids and then
heat-treated it. The well-known material Interpore 500
also contains β-TCP and can be prepared by reacting
the carbonate skeleton of coral with (NH4)2HPO4 and
H3PO4 solutions [12]. To prepare gradient ceramics,
with the mineral composition varying with depth, dia-
mond powder is applied to an HA workpiece before fir-
ing. Burning of the powder leads to HA decomposition
into TCP on the surface [13].
TCP may also result from the reactions accompany-
ing sintering of HA. The polycrystalline ceramics fab-
ricated by Osborn [14] contained 70–95% rutile, HA,
and TCP, which results from the decomposition of HA
powder in the range 1200–1300°C and is present in the
form of a grain-boundary phase.
Yoshio et al. [15] produced high-porosity ceramics,
with the skeleton built from long TCP fibers, by sinter-
ing the products of acidic leaching of 46CaO · 54P2O5
ultraphosphate glass.
The objective of this work was to study the thermo-
These observations are consistent with the physico- chemical decomposition of stoichiometric HA into
chemical characteristics of these compounds in solu- β-TCP. This process might offer a means of controlling
tion: the solubility of TCP is one order of magnitude the bioactivity of apatite-containing implant materials
0020-1685/01/3702-0180$25.00 © 2001 MAIK “Nauka/Interperiodica”

BIOCOMPATIBILITY OF APATITE-CONTAINING IMPLANT MATERIALS
181
via the production of polymineral composites incorpo-
rating calcium phosphates with different solubilities.
7
6
5
EXPERIMENTAL
HA was synthesized in aqueous solutions by neu-
tralizing calcium hydroxide (analytical grade) with
phosphoric acid (extrapure grade) at 100°C. The HA
powders thus prepared were heat-treated in a muffle
furnace, where temperature was maintained semi-auto-
matically. Phase composition of the resulting materials
was determined by qualitative x-ray diffraction (XRD)
analysis (DRON-3M diffractometer, CuKα radiation,
scan rate of 1°(2θ)/min). The β-CTP content of the
material was determined by quantitative XRD analysis
using mixtures of HA and β-TCP for calibration. The
weight fraction of β-TCP was evaluated from the inten-
sity of the peaks with d = 2.8139 Å for HA (ASTM,
9-432) and d = 2.8669 Å for β-TCP (ASTM, 9-169)
using the calibration plot of intensity vs. weight percent
of β-TCP. IR absorption spectra were measured
between 400 and 4000 cm–1 on a Specord 75 IR spec-
trophotometer using powder samples with an isopro-
panol binder. The resorptivity of the materials was eval-
uated before and after thermochemical processing from
weight loss data for 10-cm3 samples in a 0.6 N HCl
solution (USSR State Standard GOST 3118-77).
4
3
2
1
4000
3500 1500
1000
Wavelength, cm–1
500
Fig. 1. IR spectra of HA (1) before and (2–7) after reaction
with H PO and heat treatment for 1 h at (2) 200, (3) 500,
3
4
(4) 700, (5) 900, (6) 1000, and (7) 1200°C.
(brushite), which looses water of crystallization starting
at 25°C. The presence of hydrophosphate groups is evi-
denced by the prominent absorption at 875 cm–1, which
can be assigned to vibrations of the HPO42– group
(Fig. 1, spectrum 2) [16]. Increasing the temperature to
500°C gives rise to disproportionation reactions—proton
transfer between neighboring phosphate groups, without
rearrangement of ions in the crystal lattice:
RESULTS AND DISCUSSION
HA was obtained in the form of a readily agglomer-
ating white powder with a specific surface of 70 m2/g.
The size of individual needlelike crystallites was no
greater than 4 µm. According to chemical analysis and
IR absorption data (Fig. 1, spectrum 1), the Ca/P
atomic ratio in the synthesized HA was 1.67. The XRD
pattern contained only reflections from HA, indicating
that the material was phase-pure.
3HPO42–
2PO34– + H3PO4.
This process seems to be reversible, so that there is
a certain equilibrium between different phosphate spe-
In choosing the reagent for chemical treatment of
HA with the aim of obtaining calcium phosphates with
Ca/P < 1.67, we took into account the following:
Table 1. Phase composition of the products obtained by
thermochemical processing of HA in phosphoric acid (XRD
data)
The compound must contain monophosphate or
phosphorus ions.
t, °C
Phase composition
The reagent should not contain Ca in order not to
increase the Ca/P ratio.
The reagent must be volatile and readily soluble in
water.
The product of reaction between the reagent and HA
must be biocompatible and consist only of HA and
β-TCP.
All these requirements are fulfilled by phosphoric
acid. The phase compositions of the products obtained
by treating HA with phosphoric acid, followed by heat
treatment at different temperatures, are listed in
Table 1.
20
200
500
700
800
850
900
950
1200
Ca10(PO4)6(OH)2, CaHPO4 · 2H2O
Ca10(PO4)6(OH)2, CaHPO4
Ca10(PO4)6(OH)2, γ-Ca2P2O7
Ca10(PO4)6(OH)2, γ-Ca2P2O7, β-Ca3(PO4)2
Ca10(PO4)6(OH)2, β-Ca2P2O7, β-Ca3(PO4)2
Ca10(PO4)6(OH)2, β-Ca3(PO4)2
Ca10(PO4)6(OH)2, β-Ca3(PO4)2
β-Ca3(PO4)2
α-Ca3(PO4)2
At room temperature, HA reacts with phosphoric
acid to form acid calcium monophosphate hydrate
Note: The concentration of the H PO solution corresponded to a
3
4
Ca/P atomic ratio of 1.5. Reaction was run for 1 h.
INORGANIC MATERIALS Vol. 37
No. 2 2001

182
wt % β-TCP
MALYSHEVA, BELETSKII
The thermochemical method was tested on an apa-
tite-containing composite with the BAK-1000 silicate
matrix, which is used in plastic surgery [17]. The prop-
erties of this material before and after thermochemical
processing in a solution of phosphoric acid are listed in
Table 2.
100
80
The reaction between HA and phosphoric acid
involves chemical and polymorphic transformations of
calcium phosphates in the range 20–900°C. The char-
acteristic features of this process correlate with earlier
results [18]. The absence of β-TCP among the products
of reaction at room temperature indicates the necessity
of heat treatment.
60
40
1
3
5
7
9
11
wt % H3PO4
The low-temperature form of TCP is observed start-
ing at 700°C. Two-phase materials, comprising only
HA and β-TCP, can be obtained in a narrow tempera-
ture range, between 850 and 900°C. Above 900°C, the
only reaction product is β-TCP (Fig. 1, spectrum 6),
which transforms into the α-form at 1200°C (Fig. 1,
spectrum 7).
Fig. 2. Content of β-TCP after thermochemical processing
of HA in different H PO solutions at 900°C.
3
4
cies, dominated by the one which lies at the basis of the
HA structure. The HPO4– groups can be thought of as
structural defects. Heating to 500°C gives rise to con-
densation of the HPO42– groups into diphosphate
CONCLUSION
groups, as evidenced by the feature at 720 cm–1 in the
IR spectrum (Fig. 1, spectrum 3). The disappearance of
this feature and the OH– stretching band (3560 cm–1)
upon heating to 800°C (Fig. 1, spectra 3–5) suggests
The temperature range in which two-phase materi-
als consisting of HA and β-TCP can be prepared is
fairly narrow, from 850 to 900°C. The major parameter
for controlling the relative amounts of HA and β-TCP
in this temperature range is the HA/H3PO4 ratio in the
reaction system.
that, in the range 500–800°C, P2O47– groups react with
hydroxyls:
As distinct from the thermal decomposition of sto-
ichiometric HA, thermochemical processing allows
two-phase composites to be prepared below 1000°C.
By varying the concentration of phosphoric acid, one
can obtain materials containing 40–100 wt % β-TCP
and also gradient ceramics in which the composition
varies from HA to β-TCP across the implant or from
the center to the surface of the granule.
P2O47– + 2OH–
2PO34– + H2O↑.
In the range 850–900°C, the content of HA and
β-TCP after 1 h of reaction is fairly low, 45–50 wt %.
The yield of the reaction between HA and phosphoric
acid can be fine-tuned by adjusting the reagent concen-
trations (Fig. 2).
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