LICENSING OPPORTUNITY
The Warwick Implant Material with High Strength without
Compromising Cell Proliferation and Potentially Bone
InGrowth
James Meredith and Kajal Mallick
The innovation is of commercial value in the production and development of bone
substitute material. The Warwick implant material
(publication number WO2007125323 entitled “implant
for tissue engineering”) overcomes the problems of low
strength of current blocks and poor bone integration. Its
structure gives the combined advantage of compressive
strength comparable to cortical bone, cell proliferation
comparable to commercially available Orthovita’s
Vitoss® and significant porosity (60%) and open
structure to potentially allow bone incorporation and
ingrowth.
The advantages of the Warwick implant material are:
 Compressive
Strength
 Cell Proliferation
 Rapid Healing
 Biopolymer
Coating
 Manufacturing
 Complex
geometries &
sizes
 Scope
: Compressive strength is between 70-200 MPa which compares
favourably to cortical bone. Warwick implants can sustain
compressive loads of over 3 tons.
: Biological testing has demonstrated that osteoblast-like cells
(MG63) proliferate as readily as comparable material such as
Orthovita’s Vitoss®.
: The open structure with greater than 60% porosity aids in the
infiltration of blood vessels thereby increasing nutrient
transport throughout the implant. This structure promotes a
more rapid healing of bone defects than typical foam like
structures.
: The Warwick implant material can be easily coated with a drug
eluting polymer to control infection or bone morphogenetic
proteins to induce bone formation.
: Consistent, inexpensive and scaleable manufacturing.
: Custom-made complex geometries can be extruded or
machined after firing. The largest diameter product has been
40mm and could be extended further if needed. Implant
thicknesses range from 5 to 500mm. It is also possible to
manufacture complex geometries that replicate anatomical
structures.
: The structure can be applied to a range of ceramic materials
e.g. calcium phosphate ceramics such as a β tricalcium
phosphate and hydroxyapatite (HA) composite.
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Regulatory consultants confirm that the Warwick implant material is a Class III medical
device and that additional clinical testing may not be necessary for CE marking
purposes given the existing literature available for calcium phosphate implants.
The Warwick implant material is potentially suited to the following applications:





Cervical and lumbar spinal fusions where it may be subjected to mechanical
load.
Cervical spinal fusions using Cloward’s Procedure – its open structure is likely
to reduce contact stresses and prevent subsidence. The problem with current
products is that the contact area can be small and the implant can subside into
the exposed bone leading to a loss of correction and/or intervertebral spacing.
Large bone grafts - a more open structure may allow a more rapid nutrient flow
and bone ingrowth. This is technically challenging with high density HA
material as bone penetration can be slow leading to a dead zone within the
implant.
Bone tumour surgery.
Revision surgery of the knee, hip and ankle. The Warwick implant material
could replace the eroded osteolytic bone beneath the existing implants.
If you require further information on the use of this innovation within your company
please contact me on the details below.
Contact Details
Dr Shum Prakash
Business Development Manager
Email: s.prakash@warwick.ac.uk
Tel. +44 (0)24 7657 4145
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Appendix
Comparison of Mechanical and Biological Properties of
Warwick Implant Material versus Orthovita’s Vitoss®
James Meredith and Kajal Mallick
The Warwick implant material has a hydroxyapatite (HA) monolithic structure. It has
compressive strength and elastic modulus far higher than Orthovita’s Vitoss® (a commercially
available bone implant material) and approaching that of natural, healthy, cortical bone. Table 1
shows this comparison of the compressive strength and elastic modulus of Warwick implant
material with naturally occurring cortical and cancellous bone, as well as with Vitoss®.
Table 1. Compressive Strength
Warwick
Implant
Material
Material
Hydroxyapatite
Monoliths
Compressive Strength
70 – 206
(MPa)
Elastic Modulus (GPa)
1.6 – 3.0
Bulk porosity (%)
54.4 – 63.1
Channel size (mm)
1.08 – 2.53
Pore size range (µm)
0.2 – 0.5
Bone
Bone
Orthovita’s
Vitoss®
Cortical
Cancellous
β-TCP
Foam
50 – 250 [1]
1.5 – 10 [1]
0.1 – 0.6
5 – 25 [1]
8 – 28 [2]
5 – 200 [2]
0.05 – 0.9 [1]
30 – 90 [3]
1 – 900
0.001 – 0.01
88.0 – 92.4
1 – 1000
Source: [1] Liebschner & Michael (2004) Biomaterials 25 1697-1714; [2] Wang & Ni (2003) Journal of
Orthopaedic Research 21 312-319 and [3] Zhang et al. (2007) Acta Biomaterialia 3 896-904
High compressive strength is essential to provide adequate support for the skeleton without risk
of the implant fracturing due to normal physiological loads, since this is likely to result in
failure of the graft and subsequent need for revision. Matching the elastic modulus of the native
bone is important since bone remodels according to the applied stress (Wolff’s Law). For
example, an implant with too high a modulus may carry a disproportionate percentage of the
load and lead to atrophy of the host bone at the implant site.
Figure 1 is a plot of compressive strength versus elastic modulus, showing improved properties
of the Warwick implant material compared with alternative commercially available material.
The measured results for Vitoss® and the Warwick implant material are shown in grey. There is
a large range for the Vitoss® samples, as this has a foam structure and the properties of foam can
be variable. Figure 1 shows that the Warwick implant material has compressive strength and
elastic modulus comparable to dense (i.e., non-porous) biodegradable polymers and
approaching that of cortical bone and biodegradable polymers. In contrast, the compressive
strength and elastic modulus of alternative commercially available material is much lower.
Advantageously, the Warwick implant material has good compressive strength and elastic
modulus and, in addition, has a porous non-dense structure. The large channels of the Warwick
implant enable better blood transport, whilst the porous structure of the channel walls enables
the growth of new bone and fluid communication and nutrient transport to assist with this.
Figure 2 shows cell proliferation of cells seeded on the Warwick implant material was
increased when compared with the cell proliferation of cells seeded on Vitoss®, even though the
bulk porosity of Vitoss® is much higher. Vitoss® has a foam structure without the feature of
open channels.
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Figure1. Compressive Strength versus Elastic Modulus
Source: Adapted from Rezwan et al. (2006) Biomaterials 27 3413-3431
The percentage bulk porosity, as set out in Table 1, is a measure of the total density of the
implant, i.e., the percentage of the volume of the implant which is made up of air. It is
calculated (using theoretical density of the material and therefore the theoretical maximum
weight for the sample) with the formula:
 

Mass actual
  x 100
Bulk porosity  1  

Mass
Max
theoretica
l

 
From Table 1, it can be seen that the Warwick implant material displays a bulk porosity of
54-63%, which is within the range of 30-90% of cancellous bone. Surprisingly, however, as can
be seen from Figure 1, the elastic modulus and compressive strength of the implant are both
significantly improved as compared with cancellous bone. Indeed, the compressive strength is,
surprisingly, comparable with that of cortical bone, even though the bulk porosity of the implant
is at least twice as high as that of cortical bone. It would have been expected that increased
porosity would be correlated with decreased strength, as shown in Figure 1. These surprising
properties are the result of the combined features of the ordered structure, channel size and pore
size, which are achieved by producing the Warwick implant material.
Figure 2 shows the results of an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide
(MTT) assay carried out on 5 different extruded Warwick implant material (A-E) versus a
sample of Vitoss®. The MTT assay is a simple colorimetric assay used to monitor the
biochemical activity of cells. The metabolic conversion or reduction of yellow MTT to purple
formazan occurs in the mitochondria of living cells. This reduction of MTT to formazan occurs
when the mitochondrial dehydrogenase enzyme in the living cells cleaves the tetrazolium rings
in yellow MTT to form purple formazan crystals. These are impermeable to cell membranes
leading to accumulation within the living cells, this only occurs when mitochondrial reductase
enzymes are active and so the amount of reduction is directly related to the number of living
cells.
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Figure 2. MTT Assay to Monitor the Biochemical Activity of Cells
Mean Absorbance at 550 nm
2.5
A
B
C
D
E
Vitoss
2.0
1.5
1.0
0.5
0.0
3
6
9
Days of MG63 growth
Figure 3 illustrates an example of the cells growing on the hydroxyapatite monolithic structure
of the Warwick implant material. The crystals of purple formazan within the cells are
solubilised in a solution of dimethyl sulfoxide (DMSO) and the optical density (OD) or
absorbance of this coloured solution is then quantified at a specified wavelength (550nm) in a
spectrophotometer.
Figure 3. Attachment of osteoblast-like cells,
MG63, to the structure of the Warwick implant
material.
In summary, the Warwick implant material is novel and offers several improved and surprising
technical effects (elastic modulus, compressive strength, cell proliferation) over existing
commercially available materials and naturally occurring bone. These surprising properties are
the result of the combined features of the ordered structure, channel size and pore size, which
are achieved by producing the Warwick implant material.
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