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Phosphate based glasses for biomedical applications
Jonathan C. Knowles
Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College
London, 256 Gray’s Inn Road, London, UK WC1X 8LD
Received 23rd June 2003, Accepted 7th August 2003
First published as an Advance Article on the web 14th August 2003
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Biomaterials and tissue engineering are rapidly
expanding fields for research and also commercial
exploitation. A greater understanding of the interaction
of materials with cells has allowed implant materials to
be designed with the aim of promoting a specific
biological response. Phosphate-based glasses are a unique
group of materials that offer great potential for hard and
soft tissue engineering. The move from passive inert
implant materials to active degradable materials indicates
that phosphate glasses may have a role in tissue
engineering. Whilst significant work has been carried out
to elucidate the structure of these materials, there is a
paucity of data to correlate this information with the
physical properties such as dissolution rate. This paper
details some of the basic properties of these materials
and how these may be exploited in the design of a
biomaterial. Also a review of some of the current and
potential clinical uses for these materials is included.
Introduction
Biomaterials as a science is moving into a new era of implants.
Historically implants have been, and still are in the majority,
formed from metals and remain in the body for the long term.
They tend to be biotolerant, whereby the biological reaction to
these implants is at a low level. More recently, there has been
much interest in degradable materials that perform a
temporary functional role such as mechanical stabilisation of
tissue and which then degrade after the tissue has healed, but as
with the metals they tend to perform a biologically passive
function. A new and sometimes defined as ‘Third Generation’
Jonathan Knowles originally graduated in 1991 with a PhD in
Biomedical Engineering, working on degradable composites.
Following this he spent 6
months at Aichi Medical Uni-
versity as a Royal Academy of
Engineering Overseas Visiting
Research Fellow, also spon-
sored by the EPSRC. On
returning to the UK he
worked at the IRC in Biomedi-
cal Materials at Queen Mary
University of London and was
then appointed in 1995 as a
lecturer at the Eastman Dental
Institute, University College
London. He has remained at
the Eastman since then and has
recently been promoted to Pro-
Jonathan C. Knowles fessor of Biomaterials Science.
DOI: 10.1039/b307119g
This journal is # The Royal Society of Chemistry 2003
Materials
Feature Article
CHEMISTRY
of implants are being developed in which the implants not only
are temporary, but also take an active part in the tissue
regeneration process and this is encompassed in the field of
Tissue Engineering.
The National Science Foundation (NSF) defined tissue
engineering as ‘‘The application of the principles and methods
of engineering and life sciences towards the fundamental
understanding of structure/function relationships in normal
pathological mammalian tissues and the development of bio-
logical substitutes to restore, maintain or improve functions’’.1
Phosphate based glasses have many unique properties, the
most interesting of which, from a biomedical point of view, is
its ability to dissolve completely in aqueous media. Further-
more this dissolution behaviour may be easily altered via the
chemistry of the glasses to give glasses whose dissolution rate
can vary over several orders of magnitude. Of further benefit
from a biomedical standpoint is the fact that these glasses can
be synthesised to include ions routinely found in the body. The
benefits of a glass system to develop an implant can also be
exploited to give a huge range of tailored compositions
dependent on the final application.
Glass structure
Oxides used in glasses may be divided into three groups:
1. Network forming oxides. The primary network formers
are SiO2, B2O3 and P2O5. However the following compounds
may act as network formers under certain circumstances:
GeO2, Bi2O3, As2O3, Sb2O3, TeO2, Al2O3, Ga2O3 and V2O5
(the four classic Zachariasen2 network forming oxides are Si, P,
Ge and As). With the exception of GeO2, these oxides do not
readily form glasses by themselves unless rapidly quenched or
formed from vapour deposition.3 Also in chalcogenide glasses,
S, Se and Te can act as network formers and two common
halide glass formers are BeF2 and ZrF4,
2. Network modifying oxides (all oxides not found in 1 and
3), and
3. Intermediate oxides (Al, Ga, Ti, C, V, Bi, Mo, W, S, Se,
Te).
The most important group is the first. These are oxides of
elements that will form glasses by themselves and are mainly
found in Groups IV and V of the Periodic Table. In terms of
volume use, clearly silicate based glasses are by far the most
common. However the others are of interest primarily driven
by the optoelectronics industry.4–6 As can be seen from the lists
above, oxides of some elements may perform a different role
depending on the other components in the glass.
Phosphate-based glasses are a unique group of materials that
differ quite considerably from the silicate based counterparts.
This starts at the fundamental level of the network forming
oxide and is illustrated in Fig. 1.
Some work has been carried out on pure P2O5 glass, but this
is severely limited due to its hygroscopic nature.7 The study of
J. Mater. Chem., 2003, 13, 2395–2401 2395

Fig. 1 Illustration of the basic silicate and phosphate tetrahedra.
pure P2O5 as a glass is further complicated by crystalline P2O5
having three polymorphic forms: hexagonal, orthorhombic and
tetragonal. As pure P2O5 they contain phosphate tetrahedra,
but the tetrahedra form rings which have different numbers of
tetrahedra per ring depending on the polymorph. These
structures may be retained when short melting times are used
and the properties only converge when extended melting times
are applied. Therefore consistency in the use of precursor
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chemicals and processing can be paramount in obtaining
reproducible results.
Whilst oxides of silicon and phosphorus are used by
themselves, the oxides of the above elements are not routinely
processed to form glasses and silicon dioxide and phosphorus
pentoxide are interesting to compare as they have diametrically
opposed reasons for adding other components to change their
properties: silicon dioxide has a relatively high melting point
and so components are added to reduce the processing
temperatures, and phosphorus pentoxide is very reactive and
other components are added to increase its durability. Indeed,
because of its reactivity, P2O5 is widely used as a drying agent.
Binary phosphate glasses
The most commonly introduced oxides are sodium oxide
(Na2O) and calcium oxide (CaO). The role that these oxides
play can have a significant effect on the glass structure and is
explained in Fig. 2.
The above diagram also serves to illustrate the three main
building blocks in condensed phosphates, which are the Q1 or
end unit, the Q2 or middle unit and the Q3 or branching unit.
Also in terms of naming, the ratio of P2O5 to M2O can
classify them into one of four different groups:
P2O5 1 3 M2O A Orthophosphates
P2O5 1 1 to 2 M2O A Pyrophosphates
P2O5 1 1 M2O A Metaphosphates
P2O5 1 v1 M2O A Ultraphosphates
The works of Hoppe8 and also Brow and Kirkpatrick9,10 give a
significant insight into the complex structure of these glasses
and it is Hoppe’s view that in addition to the depolymerisation
process, there are other structural principles at work. For a
simple system consisting of the P2O5 network former to which a
metal oxide is added, initially there is a large excess of terminal
oxygen atoms in the pure P2O5. As the metal (M) is added, it
initially occupies positions with high M–O coordination
numbers surrounded by terminal oxygen atoms on M–O–P
bridges. However as the M content increases, a point is reached
at which all the terminal oxygen atoms occupy this M–O–P
state. As the M content is now further increased, a modified
random network develops. However it should be borne in mind
that these glasses in the system M2O–P2O5 generally tend to be
in the compositional range where the M2O content is above
Fig. 2 Effect of monovalent ion addition to P2O5 network.
2396 J. Mater. Chem., 2003, 13, 2395–2401
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30 mol%11 due to the above mentioned volatility and thus a
significant portion of the phase diagram is not available in the
literature and even up to M2O contents of 50 mol%, the
structure of these glasses remains poorly understood.
Whilst these data considerably enhance our understanding of
the structure of glasses, as highlighted by Delahaye et al.,12
little work has been carried out on the dissolution of the
phosphate glasses and indeed on the physical properties in
general.
One group of binary phosphates that are of interest are based
on sodium polyphosphates.13 The work reported binary glass
production via a postulated condensation route from pre-
cursors of varying ratios of Na2HPO4 and NaH2PO4, which
gave a range of theoretical PO432 units between 22 and 6.
However this appeared to have little effect on the degradation
rate and thus a ring opening polymerisation route which
approached equilibrium was suggested. Also work was carried
out on the in vitro biocompatibility and confocal laser scanning
micrographs (CLSM) of craniofacial osteoblast cells (CFC’s)
showed a high level of actin organisation (Type II and III,
indicative of osteoblast biocompatibility) similar to the
Thermanox control. It should be noted that the Thermanox
plastic is a plasma treated tissue culture plastic designed to
optimise cell growth.
Ternary phosphate glasses
A significant proportion of work has centred on the Na2O–
CaO–P2O5 system14,15 and in particular the (Na2O)0.552x-
(CaO)x(P2O5)0.45 system. Initial work has investigated the basic
dissolution characteristics of this glass. Whilst not presenting
an exhaustive analysis of the dissolution–composition relation-
ship, some of the major relationships can be seen in the set of
glasses mentioned above with a fixed P2O5 content of 45 mol%.
Fig. 3 shows a plot of weight loss per unit area against both
time and CaO content. In general, the inverse relationship
between CaO content and dissolution rate can clearly be seen.
The dissolution rate also appears very linear with time.
However at CaO contents of 32 and 40 mol% (Fig. 3 inset)
there is clear non-linearity in the dissolution rate, with an initial
Fig. 3 Effect of CaO content on the weight loss per unit area against
time between CaO content of 24 and 40 mol% and inset an enlargement
of the region from 32 to 40 mol%. Reproduced with permission from
ref. 14.
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Fig. 4 Change in distilled water pH with time for glasses with 8, 24 and
40 mol% CaO (45 mol% P2O5 and the balance is Na2O).
high dissolution rate which decreases significantly after about
the first 10–20 hours. Initial interpretation of this data is that
there is a two stage degradation process occurring and this is
confirmed by reanalysis of the data and application of a
diffusion model.16 Explanation of this two stage degradation
may be found in the ion release mechanism. Further detailed
analysis shows that the pH of the solution initially increases
rapidly for all glasses from a low value of 5.5 for distilled water
(Fig. 4). This plateaus for the low dissolution rate glass but for
the higher dissolution rate glasses, the pH continues to increase
and then shows a slow decrease with time. Analysis of the ion
release shows that sodium ions are released at very high
concentrations for the high dissolution rate glasses and would
indicate their preferential release from the glass structure
during the early stages of dissolution (Fig. 5). Also as expected,
the glass with the highest level of Na2O, which also has the
highest dissolution rate, also releases the highest levels of
sodium ions. This correlates with the pH values seen because as
Na1 is released, H1 migrates back into the glass to perform a
charge balancing role thus leaving an excess of OH2 and hence
the increase in pH. For the calcium ion release with time
(Fig. 6) the reverse is seen with the low calcium content glass
(the highest dissolution rate glass) releasing the highest levels of
Ca21 for all time points. It should be noted that the lag between
the pH changes and the ion measurements is probably related
to the rapid ingress of H1 ions into the glass but the slower
diffusion of ions out.
Structural information has been obtained from both FTIR
studies and also magic angle spinning nuclear magnetic
Fig. 5 Change in sodium ion concentration in distilled water with time
for glasses with 8, 24 and 40 mol% CaO (45 mol% P2O5 and the balance
is Na2O).
View Article Online
Fig. 6 Change in calcium ion concentration in distilled water with time
for glasses with 8, 24 and 40 mol% CaO (45 mol% P2O5 and the balance
is Na2O).
resonance (MAS-NMR) and in particular 31P NMR studies.
Calculation of the theoretical phosphate species and the
subsequent measurement closely correlated with the predominant
groups being Q2 (metaphosphate) and Q1 (pyrophosphate).
Glasses of the composition (Na2O)0.552x(CaO)x(P2O5)0.45
where x ~ 0.3, 0.35 or 0.4 showed both Q2 and Q1 groups.17
However for glasses in the range (Na2O)0.52x(CaO)x(P2O5)0.5
and (Na2O)0.452x(CaO)x(P2O5)0.55 only Q2 were seen indicating
a polymerisation of the glass network. Also, within the glass
compositional range (P2O5)0.45(CaO)x(Na2O)0.552x, where x ~
0.08 to 0.36, showed a shift from about 219 ppm to 223 ppm
and this may be related to the shielding on the phosphorus.
This shielding is due to the extent of the double bond and the
number of bonded cations and their electronegativity.
Significant work has been carried out on these glasses in
terms of biocompatibility and some initial cell proliferation
assays15 have been carried out via an MTT assay.18 This assay
is sensitive to the number of living cells present and is related to
the mitochondrial activity of the living cell. The substrate is
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide
and is transformed to a blue colour (and hence can be measured
spectrophotometrically at 570 nm) by active mitochondria.
Glass disks were incubated in cell culture media and after 2
days the disks were removed. This culture medium was then
used neat (1), or diluted 1 in 4 (0.25), 1 in 16 (0.0625) and 1 in 64
(0.015625). Tissue culture medium with no disk was used as a
control and the results were normalised with respect to this
value. Fig. 7 shows the MTT assay results. In general the values
are around 1, i.e. comparable with the tissue culture plastic
control. Some reduction in proliferation was seen for the high
dissolution rate glasses. However, for the high CaO content
glass, i.e. the low dissolution rate glass, a significant increase in
cell proliferation was seen even with the neat solution, by
several orders of magnitude. Consideration of the possible
reasons why, led us to speculate that the phosphate in the glass
may be playing a significant role and the reason this conclusion
is reached is if we consider the ionic content of cell culture
medium. Dulbecco’s Minimum Essential Medium (d-MEM),
as used in these assays, contains approximately 72 ppm Ca21
and 3550 ppm Na21 and thus we start to speculate that for the
low dissolution glass, it is not contributing large excesses of
Na1 and Ca21 to the medium and so it may be that the
phosphate and the form in which it is released is having a
central role to play in the cell proliferation. We are currently
investigating the form in which the phosphate is released and
the amount with time via ion chromatography.
When placed in solution, the glasses form a surface gel
layer.19 The culturing of cells on the surface (Fig. 8) has shown
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Fig. 7 Effect of glass composition and extract dilution on cell
proliferation for glasses with 24, 28, 32, 36 and 40 mol% CaO
(45 mol% P2O5 and the balance is Na2O). Reproduced with permission
from ref. 15.
Fig. 8 Growth of osteoblasts on the surface of a phosphate glass.
Evidence for encapsulation of the cells by the glass gel layer may be
seen.
evidence of cell encapsulation by this layer or the precipitation
products from the dissolution of the glass.
Work was also carried out on a K2O–CaO–P2O5 glass
system. In general the results closely mirrored those found for
the Na2O–CaO–P2O5 system. However the solubility was
found to be too high for biomedical use.
Quaternary and more complex glass systems
We have also investigated a number of other glass systems,
including Na2O–K2O–CaO–P2O5,20 Na2O–MgO–CaO–P2O5
and Na2O–CaO–CaF2–P2O5 systems. The first system was of
interest to investigate the presence of any mixed alkali effects.
This effect is particularly of interest in electrochemical devices21
and gives rise to large changes in dynamic properties and
significant deviation from linearity. Clear evidence20 for this
mixed alkali effect has been seen in the glass transition
temperature (Tg), which reduces and then increases in value as
K2O substitutes for Na2O for glasses with a fixed P2O5 content
of 45 mol%, CaO contents of 20, 24, 28 and 32 mol% and the
balance K2O and Na2O varying between 0 and 30 mol%.
Solubility behaviour for this system also differed from that seen
for the Na2O–CaO–P2O5 system in that in general the addition
of K2O appeared to make the dissolution with time more
linear. However the glasses with high CaO content also showed
a weight increase i.e. moisture uptake prior to weight loss. The
Na2O–MgO–CaO–P2O5 system will not be discussed here,
because, whilst it gave some interesting data on divalent ion
substitution in a phosphate glass structure, the biocompatibility
2398 J. Mater. Chem., 2003, 13, 2395–2401
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results were not as positive as for the Na2O–CaO–P2O5 and
Na2O–K2O–CaO–P2O5 systems. A number of glasses in the
system Na2O–CaO–CaF2–P2O5 were synthesised. This system
was of interest, because fluoride may play an active biological
role in that it is thought to stabilise the apatite structure in bone
and hence the use of fluoride in oral healthcare products. From
a practical point of view, these glasses proved to be difficult to
produce with consistent fluoride levels. Fluoride loss was
attributed to reaction with water to form HF which was then
lost to atmosphere. The volatility of fluoride is also seen in
silicate based glasses,22 where fluoride is lost as silicon tetra-
fluoride Thus when melting these glasses, the use of hygro-
scopic P2O5 was minimised. However some glasses could be
produced which released up to 14 ppm fluoride over 175 hours.
An interesting group23 of phosphate glasses are the
phosphorus oxynitrides. Improved chemical and mechanical
durability in nitrided silicate glasses is known but the use in
phosphate glasses may help to circumnavigate these limitations
in phosphate glasses. Nitride incorporation has been investi-
gated via AlN24 and Mg3N225 and more recently via ammonia
gas23 and produced glasses with an improvement in chemical
durability of between 10 and 1000 times.
Outside Tissue Engineering, the other major area of research
for these glasses is driven by their excellent optical properties.
This work uses some highly complex glass systems doped with
some unusual ions. Recent work has covered gadolinium,26
lanthanum, neodymium, samarium, europium, dysprosium,
erbium,4,5 cadmium and trivalent chromium27,28 and vana-
dium.29,30 There is also work pertaining to the use of these
glasses for immobilisation of nuclear waste via lead phosphate
glasses.31
Phosphate based glasses for degradable composites
There is much interest in the development of composites for
biomedical applications and in particular for hard tissue
surgery. The driving force for this interest is due to the
possibility of producing materials with a high resistance to
fracture (fracture toughness) as seen in bone and also to
develop implants with a stiffness close to that found in bone.
Traditional metallic implants such as bone plates for fracture
fixation have a very high stiffness compared to bone and thus
there is a modulus mismatch. This modulus mismatch means
that long term, the implant continues to support the majority of
the load imposed externally. Initially healing occurs, with the
fracture increasing in strength. However, at longer time points
resorption of the bone can occur with associated weakening
and thus the plates are usually removed. The possibility of
producing degradable composites has elicited much research
and the phosphate based glasses may be used as a reinforcing
phase to produce completely degradable composites when
combined with degradable thermoplastics,32–34 incorporated
into calcium phosphate cements35 or acrylic acid based drug
delivery systems.36 The advantage of using these glasses for the
production of composites compared to conventional stoichio-
metric additives such as hydroxyapatite37–41 is that more
variation in the composition of the glass filler phase is available
thus allowing tailoring of the end properties, including
mechanical properties and control of the overall dissolution
rate of the composite.
Phosphate glass fibres for tissue engineering
As with the bulk phosphate based glasses, the optoelectronics
industry has been a driving force in the development of these
phosphate based fibres due to the above mentioned optical
properties.42–44 These phosphate based fibres also offer great
potential for tissue engineering and in particular for any tissue
with a medium to high anisotropy, such as muscle and
ligament. Moving from the bulk glass to fibres, there are two

driving forces as to whether these fibres will perform
successfully in a tissue engineering role: the chemistry and
also now the fibre morphology.
The dissolution rate of the glasses is surface dependent so we
can already predict that whilst the bulk glasses for example
from the Na2O–CaO–P2O5 system showed positive in vitro
results, the same compositions in fibre form would degrade too
quickly for any biomedical use. This has proved to be the case,
but proved useful to investigate as the precursor glasses are well
characterised. From our initial work,45–48 fibres could be
produced from glasses in the range (Na2O)0.52x(CaO)x(P2O5)0.5,
(Na2O)0.452x(CaO)x(P2O5)0.55 and (Na2O)0.42x(CaO)x(P2O5)0.6
where x ~ 0.3, 0.35 and 0.4. However glasses in the com-
positional range (Na2O)0.552x(CaO)x(P2O5)0.45 did not pro-
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duce fibres. As mentioned previously the glasses with 45 mol%
P2O5 showed the presence of Q1 and Q2 phosphate groups,
whereas glasses with P2O5 contents of 50 and 55 mol%
showed only Q2. This would indicate an increase in poly-
merisation with increasing P2O5 content and this would tie
in with the practical ability to make fibres as a polymeric
structure would lend itself more readily to fibre production.
Fig. 9 shows an SEM of phosphate fibres. Fibres with
diameters down to 5 to 6 mm have been routinely produced.
Interestingly, when placed in a static solution, dissolution and
reprecipitation occurs and polycrystalline tubes are formed
(Fig. 10).
Initial work concerning cell viability on these untreated
ternary based glass fibres has shown limited success. Work
commenced to study in vitro the interaction of muscle cells with
the glass fibres. Whilst the bulk glasses appeared to promote
cell proliferation with the glasses containing high levels of CaO,
for the fibres of the same composition, cells were poorly
adherent. And this was due to the dissolution rate being a
Fig. 9 SEM of some typical glass fibres produced.
Fig. 10 SEM of fibres after dissolution testing, showing the formation
of polycrystalline tubes.
View Article Online
function of surface area. The muscle cell response to these
fibres has, however, been dramatically improved by the
addition of a coating layer of Matrigel. Some more recent
compositions produced have had extremely high CaO content
and have proved more successful. However, as an alternative
method for reducing the dissolution rate of the glass fibres and
hence improving the cell attachment, fibres doped with Fe2O3
have been studied. The addition of between 1 and 5 mol%
Fe2O3 dramatically reduces the dissolution rate and 4–5 mol%
was found to be adequate for cell attachment and proliferation.
Phosphate glasses for the delivery of antibacterial
ions
A number of ions are known to have potent antibacterial
properties and may also be of benefit when taking into
consideration the increasing problems with bacterial resistance
to antibiotics. These systems are ideal as one of the major
problems with drug delivery systems is the drug dumping effect
often seen, whereby an incorporated drug rapidly washes out of
the matrix material in the early stages of implantation. Because
the antibacterial ions are incorporated into the glass structure,
the ions are released in a controlled manner as the material
degrades. Work on both copper47 and silver48 using a Constant
Depth Film Fermenter (CDFF) to mimic the oral environment,
has shown that silver is a much more potent antibacterial agent
to Streptococcus sanguis. However they still show a significant
ability to recolonise the surface of these materials and form a
sacrificial barrier layer to allow further bacterial growth.
Interestingly these same ions are of interest in phosphate
glasses as they produce fast ion conducting glasses.49,50
Potential clinical applications
Bacterial control devices
As discussed previously, the glasses prove to be an effective
means of delivering high levels of antibacterial ions such as
silver and copper at a constant rate. One simple yet highly
effective device that has already undergone clinical trials is a
release device in a urinary catheter line.51 The clinical problem
associated with catheters and in particular catheters for long
term use is bacterial infection. Urine accumulating in the
collection bag is non-sterile and the bacteria can grow and
track back up the catheter. This can result in bladder infection
and the requirement for the catheter to be changed, with
associated trauma to the patient and additional cost. The silver
releasing glass has been developed as a ball which sits in a tube
in the catheter line. As urine passes over the device, it dissolves
and releases the antibacterial ions. These then help to kill
bacteria in the urine bag. Furthermore, the ball in the catheter
line also acts as a barrier preventing bacteria tracking back up
the catheter line.
Neural repair
The ability to effectively repair damaged nerves would restore
function and thus hugely enhance patients’ lives. Nerve damage
can range from loss of sensation, through mal or non-function
of a limb, to the extreme of spinal cord damage and
quadriplegia and paraplegia. Currently, small nerves can be
repaired to a certain extent by grafting, or the application of
techniques to allow nerve end regrowth, as long as the nerve
ends are not above a critical distance apart. Phosphate based
glasses in a tubular form have been proposed as a temporary
device into which the nerve endings are inserted.52,53 This
device performs a number of functions: (1) it keeps the nerve
endings aligned, (2) it prevents scar tissue forming between the
nerve endings and (3) it prevents nerves being lost to tissues
other than the target site. Furthermore the device is temporary
J. Mater. Chem., 2003, 13, 2395–2401 2399

and thus removal surgery is not required. The in vivo study52
reported that all the phosphate glass tubes had dissolved and
examination of the nerves showed that whilst the mean fibre
diameter, axon diameter and myelin sheath thickness were all
reduced compared to the control (an exposed nerve but not
severed) they were not statistically significant. Thus the
phosphate glass in this particular application appears success-
ful and may be further enhanced by the application of
neurotrophic factors within the tubes.
Oral healthcare
Fluoride releasing glasses as bone implants have been discussed
previously. However work has already been carried out to
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develop these materials for releasing fluoride into the oral
cavity to aid in remineralisation of early carious lesions54–57
and/or would be advantageous for irregular dental clinic
attenders. These devices make use of the sustained and long
term release (up to one year) of fluoride.
Haemocompatibility
The use of phosphate based glasses in blood contacting
applications is an interesting concept. The glass may be in
tubular form or perhaps as a fibrous mesh,58 but there may be
hazard associated with a degradable material depositing its
degradation products directly into the blood stream. Pre-
liminary in vitro58 studies investigated thrombus formation and
granulocyte activation and found that certain compositions
actually inhibited or prevented plasma coagulation. Whilst the
exact composition of the glasses used is not given, it could be
speculated that the compositions inhibiting thrombus forma-
tion were likely to be the higher dissolution rate compositions.
These would act by providing an unstable surface which the
cells would find difficulty becoming adherent.
Veterinary use
The phosphate based glasses have been investigated and used
extensively in a number of applications for supplementing a
variety of different species with trace elements59–66 including
cobalt, zinc and copper. This proves to be an effective
treatment as usually the animals are injected once or twice a
year with supplements. However this usually leads to a high
dosage followed by rapid excretion of the excess. The glasses
are designed to reside in the animals’ stomachs and give a
sustained release of elements with time and this can be for up to
one year.
Concluding remarks
The preceding discussion of the current status and future trends
for phosphate glasses and tissue engineering hopefully serves to
highlight the potential for these materials coupled with our
increased understanding of cell–material interactions. These
glasses may not necessarily become a routinely utilised surgical
device. However they have given us a significant insight into the
interaction of degradable materials with cells and fluids. There
are still significant gaps in our knowledge, especially when the
interdisciplinary nature of the field is considered. This extends
all the way from a basic understanding of the structure of these
glasses and an appreciation of their complexity along with
information regarding the interface between cells and the
glasses. In the future we envisage a move away from the
production of these glasses via high temperature melting routes
to low temperature sol–gel methods. This offers potential for
the production of high surface area porous materials and for
the incorporation of active molecules such as antibiotics,
growth factors and for the delivery of DNA.
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Acknowledgements
The author would like to acknowledge his co-workers,
including K. Franks, I. Ahmed, M. P. Lewis, I. Olsen,
C. Collins and V. Salih. The author would also like to
acknowledge the financial support from the EPSRC, the
BBSRC and the Lord Dowding Fund.
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