Current State of The Art of Biphasic Calcium Phosphate Bioceramics
Current State of The Art of Biphasic Calcium Phosphate Bioceramics
Current State of The Art of Biphasic Calcium Phosphate Bioceramics
We have developed 15 years ago, with the collaboration of Lynch, Nery, and LeGeros in the
USA, a bioactive concept based on biphasic calcium phosphate (BCP) ceramics. The concept
is determined by an optimum balance of the more stable phase of HA and more soluble TCP.
The material is soluble and gradually dissolves in the body, seeding new bone formation as it
releases calcium and phosphate ions into the biological medium.
The bioactive concept based on the dissolution/transformation processes of HA and TCP
has been applied to both Bulk, Coating and Injectable Biomaterials. The events at the calcium
phosphate (CaP) biomaterial/bone interface represent a dynamic process, including physico-
chemical processes, crystal/proteins interactions, cells and tissue colonization, bone
remodeling, ®nally contributing to the unique strength of such interfaces. An important
literature and numerous techniques have been used for the evaluation of the fundamental
physico chemical and biological performance of BCP concept. This type of arti®cial bone
used from a long time in preclinical and in clinical trial, revealed the ef®ciency for bone ®lling,
performance for bone reconstruction and ef®cacy for bone ingrowth at the expense of the
micro macroporous BCP bioceramics.
# 2003 Kluwer Academic Publishers
The development of calcium phosphate ceramics and Europe, Brazil, Japan, USA, Australia as a bone-graft or
other related biomaterials for bone graft involved a better bone substitute materials for orthopaedic and dental
control of the process of biomaterials resorption and applications under various trade mark (BCP1, MBCP1,
bone substitution. Synthetic bone graft materials are Triosite1, Hatric1, Eurocer1, Biceram1, Bicalfoss1
available as alternatives to autogeneous bone for repair, . . .). It is now available in blocks, particulates,
substitution or augmentation. Synthetic biomaterials customized design (Fig. 1) and as an injectable material
include essentially special glass ceramics described as in a polymer carrier (Fig. 2).
bioactive glasses; calcium phosphates (calcium hydro- BCP is obtained when a synthetic or biological
xyapatite, HA; tricalcium phosphate, TCP; and biphasic calcium de®cient apatite (CDA) is sintered at tempera-
calcium phosphate (BCP)). These materials differ in tures above 700 C. The extent of calcium de®ciency
composition and physical properties from each other and (Ca/P molar ratio 5 1.67) depends on the method of
from bone [1±4]; and must be take into consideration for preparation (by precipitation, hydrolysis or mechanical
more ef®cient bone ingrowth at the expense of the mixture), the reaction pH and temperature in the
biomaterials and to adapt to new development of preparation of the unsintered apatite. The calcium
dedicated biomaterials. de®ciency determines the HA/b-TCP ratio in the BCP.
We have developed 15 years ago, with the collabora- The HA/b-TCP ratio in the BCP determines its reactivity
tion of Lynch, Nery, and LeGeros in USA, a bioactive [6, 8±10]: the lower the ratio, the higher the reactivity
concept based on BCP ceramics. The concept is (expressed in vitro as the extent of dissolution in an acid
determined by an optimum balance of the more stable buffer). Particle size, macro porosity and micro porosity
phase of HA and more soluble TCP. The material is (Figs. 3(a) and (b)) are also factors in the reactivity of
soluble and gradually dissolves in the body, seeding new BCP. Sintering temperature and conditions affect these
bone formation as it releases calcium and phosphate ions properties.
into the biological medium [5±8]. BCP bioceramics The interest of BCP concept is the controlled
consists of a mixture of hydroxyapatite (HA), dissolution and due to the structure, the bone ingrowth
Ca10 (PO4 )6 (OH)2 and beta-tricalcium phosphate (b- at the expense of the ceramic. Between 1920 and 1975, a
TCP), Ca3 (PO4 )2 of varying HA/b-TCP ratio. LeGeros very limited number of scienti®c articles reported that the
initiated in USA basic studies on preparation of BCP and use of calcium phosphate materials, described as
their in vitro properties in 1986 and Daculsi in France. At ``tricalcium phosphate'', to repair bone defects success-
the present time, BCP is commercially available in fully promoted bone formation [11, 12]; or periodontal
0957±4530 # 2003 Kluwer Academic Publishers 195
Figure 1 MBCP1 block, granules, cylinders, wedges and customized
design available for bone reconstruction.
Cellular events
The BCP materials elicit responses from bone cells and
related cells in vitro and in vivo that are similar to those
elicited by bone. These materials allow cell attachment,
proliferation and expression. The ®rst biological events
after BCP ceramics implantation are biological ¯uid
diffusion, followed by cells colonization. These cells are
macrophages, in early steps, followed by mesenchymal
stem cells, osteoblasts, osteoclasts, into the macropores
of the implants (Fig. 4). The resorbing cells forming both
Figure 4 Newly formed bone into MBCP2 or Triosite1 macropore in
at the surface of the newly formed bone and the femoral epiphysis of rabbit after 14 days of implantation showing
bioceramic surface looks like osteoclast and are TRAP osteoclasts (arrow) and osteoblasts. Decalci®ed section stained with
positive (Fig. 5). In human spine arthrodesis we have Masson's Trichromic staining.
196
Figure 5 TRAP staining of osteoclast in femoral epiphysis of rabbit Figure 8 MBCP1 granules implanted 2 weeks in muscular area of
after 14 days of implantation. rabbit. Non-decalci®ed section with Movat's staining.
Figure 6 Human spine arthrodesis using Triosite1 blocks after 3.5 Figure 9 Bone reconstruction into MBCP1 implant associated with
months of implantation showing bone ingrowth at the expense of the autologous bone marrow and implanted in 65 grays irradiated femoral
Triosite1 (Tr) with osteoclast (arrow) near vascular channel (C). canine bone defects.
formed cartilage without ®brous encapsulation (Fig. 7). Netherlands [16]. This property can be used for arti®cial
Moreover, in non osseous site after implantation in sub- bone in irradiated implantation site. Irradiation produces
cutaneous area, we have sometimes observed into some irreversible effects on normal tissues, involving damages
macropores of micro macroporous biphasic calcium on their reparation properties. Nevertheless quality of life
phosphate (MBCP1) osteoid formation (Fig. 8). These of patients who undergo radiotherapy could be improved
observations suggest that BCP with macropores present by bone reconstructions. A preclinical study performed
suitable chemical environment associated to ef®cient in irradiated dogs demonstrated bone ingrowth at the
architecture able to catch mesenchymal stem cells and to expense of structured implants of micro macroporous
induce their phenotype to osteogenic cell lines. These biphasic calcium phosphate ®lled by autologous bone
observations have been also described by other groups in marrow after implantation in irradiated soft and bone
tissue [17] (Fig. 9).
198
incorporating ions ( principally carbonate) from the
biological ¯uid during its formation; (3) association of
the carbonate-apatite crystals with an organic matrix; and
(4) incorporation of these microcrystals with the
collageneous matrix in the newly formed bone (in
osseous sites). The events at the CaP biomaterial/bone
interface represent a dynamic process, including phy-
sico-chemical processes, crystal/proteins interactions,
cells and tissue colonization, bone remodeling, ®nally
contributing to the unique strength of such interfaces.
These type of arti®cial bone revealed from a long time in
preclinical and in clinical trial the ef®ciency for bone
®lling, performance for bone reconstruction and ef®cacy
for bone ingrowth at the expense of the micro
macroporous biphasic calcium phosphate bioceramics.
Figure 13 Cancellous bone formed into rabbit femoral epiphysis after 3
weeks of implantation of IBS1 (Movat's staining).
Acknowledgment
The individual and collaborative studies were supported
by research grants from the INSERM U225, CJF 93-05
and E 99-03 and CNRS EP 59 (Dr G Daculsi, Director)
and from the National Institute for Dental Research of the
National Institutes of Health Nos. DE04123 and
DE07223 and special Calcium Phosphate Research
Funds (Dr RZ LeGeros, Principal Investigator). The X-
ray microtomography and 3-D imaging have been
performed with the ESFR Grenoble France facilities.
We thank BIOMATLANTE (Vigmeure ok Bulagne
France) and ZIMMER France for samples providing.
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