Types of bone grafts
Autografts: bone from the same individual (the gold
Allografts: another individual of the same species.
Xenografts: bone from different species, usually bovine
and coral origin.
Alloplast: synthetic material.
Disadvantages of autografts
Morbidity at the donor site.
Limited availability of bone.
Require a second surgery at the donor site coupled
with additional surgical risks, bleeding and possible
Expensive procedure due to the prolonged hospital
stay and extended medicare.
Disadvantages of allografts & xenografts
Do not provide viable osteogenic cells
Possible immune response.
Disadvantages of synthetic HA (stoichiometric &
Very slow resorbability. Long-term complications
include detachment of the coating from the implant
and peri-implant infection, as HA is known not only
as a bioactive mineral but also as an adsorbent. In
other words, HA can adsorb bacteria.
Osteoconduction means that bone grows on a surface.
Osteoconductive surface is one that permits bone
growth on its surface or down into pores or channels.
Osteoinductive material has the ability to induce bone
formation by instructing its surrounding environment
to form bone.
Osteoinduction involves the stimulation of
osteoprogenitor cells to differentiate into osteoblasts
(bone-forming cells) that then begin new bone
Another proposed definition of osteoinduction is
the process by which osteogenesis is induced.
Osteogenesis is the process of new bone formation.
Osteointegration describes a process whereby clinically
asymptomatic rigid fixation of alloplastic materials is
achieved, and maintained, in bone during functional
(Albrektsson T, Johansson C. Osteoinduction, osteoconduction
and osseointegration. Eur Spine J 2001; 10: S96–S101)
Table 1: Existing calcium phosphates (CaPO4) and their major properties.
Calcium phosphate cement (CPC) consists of one or
more calcium phosphate powders, which upon mixing
with water or an aqueous solution form a paste that is
able to set and harden forming either a non-
stoichiometric calcium-deficient hydroxyapatite (CDHA)
or brushite (dicalcium phosphate dihydrate, DCPD).
Apatite-forming CPCs Brushite-forming CPCs
TTCP + DCPA/DCPD
β-TCP + MCPM/MCPA
End-product: CDHA End-product: DCPD
Better solubility under
Faster reaction & setting
& resorption in vivo
Most commercial products
After hardening, all formulations can form only two
Calcium-deficient hydroxyapatite (CDHA) at pH > 4.2
or brushite (DCPD) at pH < 4.2.
Manual mixing: using a mortar and either a pestle or
Disadvantage: insufficient and inhomogeneous
mixing thus compromises the strength.
Mechanical mixing: Better.
Applied by the fingertips of a surgeon or
injected from a syringe.
Besides having excellent biological behavior, being
injectable and self-setting in vivo at body
temperature are the two main advantages of CPCs
as bone substitutes.
1. Setting time
Factors which could reduce the setting time
(i) Smaller particle size (high specific surface area)
(ii) Low crystallinity
(iv) Higher setting temperature
(v) Low liquid-to-powder ratio (L/P ratio).
2. Cohesion and anti-washout ability
Cohesion is the ability of a paste to keep its
geometrical integrity in an aqueous solution.
A bad cohesion may prevent setting and may lead to
negative in vivo reactions due to the release of
Another definition of cohesion is the ability of a CPC
to harden in a static aqueous environment without
disintegrating into small particles.
The definition of the ‘‘anti-washout ability’’ is
similar to that of cohesion, except that the former is
evaluated in a dynamic aqueous environment.
Numerous biopolymers, such as sodium alginate,
hydroxypropyl methylcellulose (HPMC), hyaluronic
acid, chitosan and modified starch, can significantly
improve the cohesion and anti-washout of CPCs.
The two best methods to increase the cohesion
(i) Smaller particle size
(ii) Increasing the viscosity
However, they may in some cases compromise the
setting time and mechanical properties.
Injectability is defined as an ability of a formulation
to be extruded through a small hole of a long needle
(e.g., 2 mm diameter and 10 cm length)
Inj = (WF − WA)/(WF − WE) × 100%
Inj is the percentage injectability
WF is the weight of the full syringe
WA is the weight of the syringe after the injection.
WE is the weight of the empty syringe
Factors which could increase the injectability
(i) Increasing the L/P ratio
(ii) Decreasing the viscosity
(iii) Smaller particle size
(iv) Round particles
CPCs can be prepared with compressive strengths
comparable to those reported for human cancellous
bone (4-12 MPa) or cortical bone (130-180 MPa).
The strength decreases globally with increasing
With comparable porosities, apatite cements
generally have higher strengths than brushite
In similar conditions, dry samples have a higher
strength than wet samples.
The smaller the particle size of the starting
materials, the faster they will convert into apatite
and the smaller the apatite crystals formed, which,
in turn, will lead to more and dense crystal
entanglement and thus to an increase in strength.
A general conclusion is obtained: crystalline
structures that are more compact and
homogeneous, with smaller crystals, seem to give
better mechanical properties than less compact or
less homogeneous ones with larger crystals.
It is difficult to increase strength of the self-setting
CPCs without having a negative influence on the
4.2. Fracture toughness
Fracture toughness (KIc) is a property which is used
to describe the ability of a material containing
cracks or notches to resist crack propagation.
CPCs have low fracture toughness (typically KIc < 0.5
KIc values are comparable to the reported values for
cancellous bone (0.1-0.8 MPa.m1/2), but much lower
than those for cortical bone (2-12 MPa.m1/2),
indicating that more effort is still required to increase
the fracture toughness of CPCs for their application
in load-bearing locations.
Carbon nanotubes (CNT) and multi-walled carbon
nanotubes, which find wide applications in sintered
HA–CNT composites, have also been used as
reinforcing agents in CPCs.
By adding certain amounts of apatite seeds, the
setting time of CPCs decreased and the compressive
strength concomitantly increased; conversely,
however, excess apatite prolonged the setting time
and decreased the compressive strength.
Incorporation of 10 wt% CaCO3 causes a decrease in
crystallite size and improved compressive strength
by a maximum of 40% compared to samples free of
Hydroxyl acids (citric acid or glycolic acid) and their
salts (sodium citrate), which allow easier mixing of
the cement and processing with a decreased L/P
ratio (relating to a decreased porosity), thus
resulting in improved strength.
However, these additives generally have optimal
concentrations that can be used in the cement,
whereas a higher concentration of such additives
can decrease strength.
The incorporation of fibers into brittle cement
improves fracture toughness as well as tensile and
In the fiber-added composite cements for civil
engineering, three mechanisms of fiber
reinforcement (fiber bridging, crack deflection and
frictional sliding) appear to be operative (Fig. 2).
Fig. 2. Schematic illustration showing three mechanisms of fiber reinforcement
(fiber bridging, crack deflection and frictional sliding) in fiber-added composite cements.
Specifically, first, when the matrix starts to crack,
the fibers bridge the crack to resist its further
opening and propagation.
Secondly, crack deflection by the fibers prolongs the
distance over which the crack propagates,
consuming more energy in newly formed surfaces.
* These two mechanisms have also been reported to be
the major contributors to the fracture toughness of
human bone, which is a composite consisting of hard
mineral nanoparticles (carbonated apatite) and a
fibrous polymer (collagen).
* Finally, the frictional sliding of fibers against the
matrix during pullout further consumes the applied
energy and increases the fracture resistance of the
Due to the chemical similarity between CPCs and
cements for civil engineering, it is strongly expected
that, by adding fibers, the above toughening
mechanisms can also be achieved in CPCs.
A fiber with a high tensile strength is essential.
Fiber length, volume fraction, orientation and
fiber/matrix adhesion, are also critical for the final
properties of the composite.
The mechanical properties gradually increased with
increasing fiber volume fraction.
However, a plateau or a decrease following the
increase was often observed in the mechanical
properties at high fiber volume.
This is mainly because the high volume of fibers may
compromise their workability, making it difficult for
them to be mixed and wetted by the CPC paste,
leaving space between fibers and matrix.
A similar evolution in mechanical properties was
also found in CPCs with increasing fiber length. The
authors ascribed the decrease in mechanical
properties to the heterogeneous distribution of the
The addition of chitosan lactate into the CPCs
produced a stronger matrix to support the fibers to
better resist crack propagation.
Types of fibers
Non-resorbable fibers: collagen fibers, polyamides,
carbon fibers and glass fibers.
Resorbable fibers: natural or synthetic polyesters
such as polylactide (PLA), poly(lactic-co-glycolic acid)
(PLGA) and polycaprolactone (PCL) or chitosan.
The incorporation of non-resorbable fibers into
resorbable CPCs could cause fiber release into the
surrounding tissues, with the subsequent
As for resorbable fibers, macropores produced from
fiber degradation can promote bone ingrowth.
However, these macropores are detrimental to the
mechanical stability of CPCs before new bone grows
into the pores.
To solve this problem, several types of fibers having
different resorption rates could be used
simultaneously. The fast degradable fibers create
pores for bone ingrowth, while fibers with a low
degradation rate provide strength to the implant.
Brushite-forming CPCs are soluble in physiological
conditions, and therefore they degrade and resorb
in vivo faster than apatite-forming CPCs.
It might take from 3 to 36 months for different
formulations to be completely resorbed and
replaced by bone.
At physiological pH, the in vitro solubility of DCPD is
approximately 100 times higher than that of β-TCP;
roughly, the same order of magnitude applies for the
in vivo resorption kinetics of these calcium
Porosity of self-setting calcium orthophosphate
formulations is a very important factor for their
Osteoclastic cells degrade the hardened calcium
phosphates layer-by-layer only (from outside to
inside) due to lack of macroporosity and
Active resorption: by the cellular activity of
macrophages, osteoclasts and other types of living
Passive resorption: due to either dissolution or
chemical hydrolysis (brushite-forming formulations
Dissolution might be both chemical and physical.
The former occurs with calcium phosphates of a low
solubility (those with Ca/P ratio > ~1.3).
The latter occurs with calcium phosphates of a high
solubility (those with Ca/P ratio < ~1.3).
For example, for MCPM, MCPA, DCPD and DCPA the
solubility product are several times higher;
therefore, they might be physically dissolved in vivo,
which is not the case for α-TCP, β-TCP, CDHA, HA
Therefore, biodegradation of the latter materials is
only possible by osteoclastic bone remodeling and is
limited to surface degradation since cells cannot
penetrate the microporous structure.
Osteoclastic cells resorb calcium phosphates with
Ca/P ratio > ~1.3 by providing a local acidic
environment which results in chemical dissolution.
1) Self-setting ability in vivo.
2) Can be injected directly into the bone defects,
where they intimately adapt to the bone cavity
regardless its shape (injectable, moldable & perfect
Note: Being injectable and self-setting in vivo at
body temperature are the two main advantages of
CPCs as bone substitutes.
3)Minimal invasive surgery, quicker recovery & less
pain. Shorter hospital stays cheapen the expenses
4) Biocompatible, bioactive & osteoconductive.
5) Bioresorbable & can be replaced by newly formed
6) Can be loaded with drugs (drug delivery system).
7) Easy manipulation.
1. Brittleness and low fracture toughness limit their
application to non-stress bearing areas.
2. Lack of macroporosity and interconnected pores,
which prevents fast bone ingrowth, and the
cements degrade layer-by-layer from the outside to
3. Can washout from surgical defect if excess of blood.
Compression during setting is recommended. In
addition, formulations containing sodium alginate
have been studied to solve this problem.
Unfortunately, the perfect grafting material does not
exist. The self-setting CPCs are not an exception to
Bone substitute &repair of bone defects in non-
stress bearing areas, e.g., craniofacial applications.
Bone filler for gaps around oral implants.
Drug delivery system: for the treatment of bone
diseases, e.g., tumours, osteoporosis and
osteomyelitis, which normally require long and
Other dental applications
*Direct pulp capping: Compared to calcium
hydroxide, both materials were equally capable of
producing secondary dentin at ~24 weeks.
1. Two liquids or pastes
3. Premixed CPC
4. Fibers having different resorption rates
1. Two liquids or pastes
An aqueous one and a non-aqueous one based on
Advantage: easier to homogenize than powder with
Twin-chambered syringe that allows injection
immediately after mixing.
* More homogenous mix without air bubbles.
* More reproducible.
* Immediate injection into the bone defects.
* Less contamination risks.
3. Premixed CPC (water-settable cement)
Already prepared paste, which is stored until use.
A non-aqueous but water-miscible liquid is used to
prepare the paste.
Hardens after being injected into the bone defect.
Advantages: fast & no mixing.
Disadvantages: sensitive to moisture during storage
& poor mechanical properties.
4. Fibers having different resorption rates
The fast degradable fibers create pores for bone
ingrowth, while fibers with a low degradation rate
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3. Chow LC. Next generation calcium phosphate-based biomaterials.
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