20
R Geoff Richards
Implant surfaces:
Do they have any relevance
to the surgeon?
What happens when an implant surface is placed into the
body? When inserting a plate, nail, screw, cage, or any other
internal fracture fixation (IFF) device into the body, regard-
less of the material, the implant is coated almost immediately
(within seconds) with a proteinaceous film upon contact with
blood. The proteins come from the blood and provide a provi-
sional matrix for the cells to adhere to. The cells never see the
actual implant surface but this matrix which has adsorbed to
the surface. The surface can determine which proteins absorb
and the orientation of their attachment. Cell adhesion then
usually follows within minutes (fibroblasts and macrophages)
followed by either soft-tissue adhesion or matrix adhesion and
eventual mineralization.
The molecular events at the surface-body interface are con-
trolled by surface properties. In an example of a metal used in
IFF (Fig 1), the actual surface is not the metal but a continu-
ally changing oxide surface. Metal ions diffuse at different
rates into the oxide and oxygen diffuses from the oxide into
the bulk metal. Biological ions are incorporated onto the oxide
along with protein adsorption. The proteins undergo confor-
AODIALOGUE 1 | 07
mational changes over time. All these processes are influ-
enced by: surface topography, greater texture exposes more
discontinuities for interaction with proteins; surface chemis-
try, determines types of intermolecular forces, governing in-
teraction with proteins; surface hydrophobicity, determines
which and how much proteins bind; surface heterogeneity
(nonuniformity), different domains interact differently with
proteins; and surface potential, influences the distribution of
ions in solution and interaction with proteins. The protein
size, charge, and stability affect both the rate of arrival to the
surface and interaction with it. Blood (which has more than
150 proteins) interacts with the surface with albumin being
the most concentrated, having a moderate size (66KD) domi-
nating initial interactions. Fibrinogen (340KD), which has a
lower concentration in the blood has a rate of arrival at least
one hundred times slower, but usually dominates the surface,
exchanging with the faster and weaker bound albumin due to
its greater affinity. This is a very simple view of protein inter-
actions with a surface, but gives an idea of the dynamics of the
biological interactions.
expert zone
ta lions
Fig 1 An implant surface is never static within the body and undergoes
continual changes over time, even without mechanical abrasion.
What happens at a soft tissue–implant surface interface?
Internal fracture fixation (IFF) implant surface finishes vary
from electropolishing of stainless steel to microrough com-
mercially pure titanium (cpTi) and Titanium-6%Aluminium-
7%Niobium alloy (TAN). TAN is used in LISS plates, locking
screws, and nails and is often mistakenly referred to as tita-
nium by surgeons. In the context of soft tissue, represented in
vitro by fibroblasts, members of my group found rough verses
smooth titanium and steel does not significantly affect fibro-
blast cell adhesion or subsequent growth. Polished TAN also
promoted fibroblast cell adhesion and growth; however both
aspects were seriously compromised on microrough TAN.
Specific aspects of the TAN topography were implicated (rough
beta phase particles within the softer alpha phase matrix),
however, the contribution of its unique surface chemistry to
the cell behavior was unknown. The observation of lower ad-
hesion, spreading, and growth on the surface of standard mi-
crorough TAN necessitated the design of a series of experi-
ments to help distinguish between the effects of material and
those of topography. Coating the standard test materials with
a uniform chemistry provided a practical model to investigate
how surface chemistry and the various topographies interact
in their effect on cells. These experiments eventually drew to
the conclusion that behavioral cues for fibroblasts on metal
implant surfaces were generally confined to the influence of
surface topography over the cue of surface chemistry.
Soft tissues, which are more sensitive to differences in im-
planted materials than bone, can react much quicker to prob-
lematic surfaces and are therefore good biocompatibility mod-
els. Early soft tissue integration with vascularization at the
21
Metal/oxide ion diffusion
Ca
Biological ion incorporation
P
Protein absorption
Protein conformational changes
tissue-implant interface, without liquid filled capsule forma-
tion is often desirable. If a bone is fixed subperiosteally and
the implant is not integrated fully, movement between the
implant and tissue interface may cause the formation of a fi-
brous capsule around areas of the implant which may become
liquid filled. Liquid filled soft tissue fibrous capsules are not
desirable, as they prevent tissue integrating with the implant
and encourage infection because they may reduce vascular-
ization at the biomaterial tissue interface causing the creation
of an immunoincompetent zone and an ideal place for patho-
gen proliferation. Consequently, immune cells are less able to
defend the body against any bacteria that have entered at the
biomaterial tissue interface. Movement of the implant also in-
fluences fibrous encapsulation and may hinder fast integra-
tion into the body and also attract more inflammatory cells to
the site.
Where gliding tissues are concerned, it is thought that a non-
adhering fibrous capsule on the soft tissue side of an IFF im-
plant may reduce the chance of gliding tissues —such as mus-
cles and tendons—adhering to the implant. One example that
requires neighboring tissues to freely glide over the implant is
within orbital fractures where connective tissues should glide
freely and not adhere to the implant surface, or problems with
eye movement can occur. In the case of overlying tendons in
distal radius fracture treatment, current literature describes
how titanium and its alloys tend to lead to more intratendon
inflammatory reactions when compared to steel, leading to
tendon-implant adhesion, tendon damage which prevents
normal tissue motion and may cause limited palmar flexion,
and even tendon rupture. The intrusion of a plate can produce
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friction for the gliding tissue and is liable to become a site for
tissue adhesion and inflammation. These osteosynthesis ap-
plications require the development of surfaces that prevent
soft tissue attachment and irritation, allow tissue gliding, but
maintain their biocompatible properties. It is highly unlikely
that a liquid filled void could occur within these situations,
due to the large movements of the gliding tissues. One way to
reduce the tissue adhesion would be to reduce surface micro-
roughness of the plate in contact with the tissue. Our work
strongly indicates that the surface topography of the titanium
(or even titanium alloy such as Ti15MO, used in hand sur-
gery), rather than the material itself is responsible for this
problem and polishing of the surfaces of plates in contact with
gliding tendons could prevent it. X-ray photoelectron spec-
troscopy results showed that the surface chemistry of anod-
ized polished metals (titanium and its alloys) did not differ
from the chemistry of the standard (as used in clinics) micro-
rough metals. Therefore, the polishing method tested should
be suitable for clinical use, where soft tissue adhesion is not
desired.
Bone With long term or permanent implants, such as spine
cages or chondylar plates in CMF, osseointegration is vital to
their success. Bony integration is increased on implant sur-
faces with higher amounts of microroughness and this is also
seen in the areas of prosthetics (hips and knees) and dentistry
(stents). The majority of research within these areas is into
increasing bony integration.
IFF devices are often removed to avoid: growth disturbances
in pediatrics; delayed infection; implant migration/breakage;
allergic reactions; soft tissue irritation; implant protrusion/in-
trusion (eg, into a joint); build up of fretting particles in unre-
lated organs (from loose multi component implants), as well
as being cosmetically disturbing (protrusion under skin). The
necessity of IFF implant removal is chiefly within the pediat-
ric population. Advocates of life long retention maintain that
difficulty in removing a device due to extraosseous formation
warrant their preservation to avoid complications such as in-
creased operative time, blood loss, and debris contamination.
AODIALOGUE 1 | 07
Fig 2 Scanning electron microscope images of
S aureus bacteria adhered to a) standard micro-
rough TAN, The bacteria are scattered all over
the surface in small clumps of 6 bacteria, b)
electropolished TAN. Bacteria are found to clump
in large clumps, with no small clumps of 6 or less
seen.
Problems associated with excessive bony overgrowth account
for ~7% of all complications encountered. In temporary im-
plants such as plating, nailing with the use of screws or the
application of external fixators, minimal bone bonding to im-
plants is desirable for the least traumatic explantation. Strong
bony integration is a disadvantage when considering removal
and the surface microstructure is the major determinant of
this.
Our in vitro work with osteoblasts has shown that surface
polishing acts on a cellular level in that implant surface topog-
raphy influences both osteoblast proliferation and differentia-
tion. We have shown that surface polishing can significantly
reduce expression of osteocalcin, a principle factor involved in
bone mineralization, thus essentially inhibiting the cells abil-
ity to mineralize and form a mature matrix. Moreover, an in-
verse relationship has been observed between osteocalcin
gene expression and total DNA content, indicating a less dif-
ferentiated osteoblast phenotype to be present on polished
smooth samples. The polishing therefore reduces subsequent
mineralization which shows that there is more to surface pol-
ishing than simple macro changes for friction of surface
roughness on the bony integration.
Our recent in vivo work assessed the effect of surface topogra-
phy of TAN and titanium (cpTi) screws with different surface
topographies (polished and microrough) in a sheep cortical
(tibial) and cancellous (rib) bone model over three time peri-
ods of 6, 12, and 18 weeks. The effect of implant topography
on bone adherence was evaluated mechanically by measure-
ment of the peak torque removal force and histologically to
assess the amount of bone present at the surface of the im-
plant. The results demonstrated that polishing both cpTi and
TAN resulted in lower removal torque than standard micror-
ough screws when placed into cancellous bone. Polished cpTi
screws also had a lower removal torque when implanted in
the cortical bone. Polished TAN screws did not have a signifi-
cantly reduced removal torque when implanted in the tibia
but at 12 and 18 weeks, there was a trend for a reduction in
removal torque. Histologically, the polished screws consis-
expert zone
tently demonstrated a lower percentage of bone contact than
the standard microrough implants. This study demonstrates
that polishing can reduce removal torque and the percentage
of bone contact in vivo and thereby improve the ease of re-
moval of TAN and cpTi screws placed into cortical and cancel-
lous bone. Where nonpermanent implants are concerned,
having some fibrous material present (as in the case of these
polished cpTi and TAN screws) may be advantageous—be-
cause it can prevent the screw from becoming completely
overgrown by bone, allowing for easier removal without com-
promising its stability within the bone (which is based upon
thread design more than surface structure).
Current in vivo work in our group looks at locked-screw and
plate combinations since many removal problems have been
noted with various designs of such systems. TAN is commonly
used for screws (and plates with LISS) with cpTi being used for
the LCP plate. We believe that excess bone bonding to these
implants is the major cause of the difficulty in removing the
screws from the plates. The purpose of the study is to assess
the effect of surface treatment of LCPs upon direct bone con-
tact after 6, 12, and 18 month implantation times in sheep
tibial cortical bone. We anticipate that the polished surfaces
will demonstrate decreased bone bonding and decreased ex-
traction forces. The results of this investigation could have sig-
nificant impact on the surface design of locking-head screws
and LCP plates to avoid the clinical problems during removal
of the implant. A second area we are working on is intramed-
ullary nailing. IM nails are composed of either stainless steel
or TAN. TAN is preferred due to its better biocompatibility and
mechanical properties. However excess bone bonding to the
TAN nails, resulting in difficulty in their removal has been
described. TAN has a microrough surface since the alloy is a
mix of soft α and harder ß phases which gives a micro spiked
morphology after surface processing. This surface integrates
extremely well with bone (as shown in our previous work
with cortical screws in vivo and discs in vitro). We know that
polishing TAN smoothes these micro spikes within the TAN
surface, which should reduce the amount of direct bone con-
tact for the nails as well as removal torques. The difficulty in
removing nails due to excess bone on-growth has not been
described for steel, which is clinically used with a smooth sur-
face. After a 12 month implantation period the nails will be
extracted by a pull-out test and some nails will remain in situ
for histomorphometric evaluation. We anticipate that the pol-
ished TAN nails will demonstrate decreased bone bonding
and extraction forces. This finding could be used to recom-
mend changes to current surface treatments of intramedul-
lary nails to reduce complications seen with nail removal, es-
pecially in rapidly growing bone in pediatrics.
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Infection Surfaces of IFF implants are generally designed to
encourage soft and/or hard-tissue adherence, eventually lead-
ing to tissue integration. Unfortunately, this feature may also
encourage bacterial adhesion. Soft-tissue infections and os-
teomyelitis are serious complications associated with im-
plants, particularly with open fractures, external fixation de-
vices, and intramedullary nailing. Consequences of implant-
associated infections include prolonged hospitalization with
systemic antibiotic therapy, several revision procedures, pos-
sible amputation, and even death. Serious complications are a
great problem due to the emergence of antibiotic resistant bac-
teria such as methicillin-resistant Staphylococcus aureus
(MRSA). Hence modifying the actual metal implant surface to
inhibit or reduce initial bacterial adhesion may be an option.
Our recent work has looked at visualization and quantifica-
tion of Staphylococcus aureus, Staphylococcus epidermidis, Strepto-
coccus mutans, and Pseudomonas aeruginosa adhering to various
surfaces including standard microrough cpTi and TAN sur-
faces, electropolished cpTi and TAN surfaces, and standard
electropolished stainless steel. Significantly more live bacteria
were observed on standard microrough TAN surfaces than on
the other metal surfaces. There was no significant difference
in the amount of bacteria found on the other surfaces. Such
an observation suggests that the standard microrough TAN
surfaces encouraged S aureus adhesion, and could lead to
higher infection rates in vivo. Hence polishing TAN surfaces
could be advantageous in osteosynthesis areas in minimizing
bacterial adhesion and lowering the rate of infection. In the
case of infection prevention chemistry and alternative tech-
nology with active biological surface modifications for pre-
vention of bacterial adhesion and infection at the implant site
will have a stronger future than pure topographical modifica-
tion.
Fig 3 Modified universal humeral
nails used in our current study on
nail removal. Left, polished test TAN
nail with mirror like surface, middle,
standard microrough surface TAN
nail with matt surface, and right,
polished standard surface steel nail
with smooth surface.
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We have developed topographies to answer clinical questions
without having to worry about shelf life and other concerns
with chemical/biological modifications. Topographical modi-
fications can be robust, cheap, and permanent, whether in
storage or in the body and (in the case of metals) can override
other cues of information to the cell such as chemistry. This
gives topographical surface modification a good solid platform
to start from. On top of this, topographical surface modifica-
tions, unlike chemical modifications, should not need extra
approval before clinical use. Polishing various implant sur-
faces has the potential to reduce the torque required for their
removal, reduce soft tissue problems, and in the case of TAN,
reduce bacterial attachment.
In situations with either hard or soft tissue interactions with
biocompatible bulk materials, the ‘implant biocompatibility’
is determined more by the design and surface characteristics.
Without surface modification an implant may be biocompati-
Geoff, whose degree was in cell and immunobiology, com-
pleted a masters in electron microscopy and received a PhD in
cell adhesion at The University of Wales, Aberystwyth. He has
authored over 50 peer reviewed papers and more than 200
abstracts, has 1 patent and 2 are pending. He has supervised 6
PhDs, 13 masters, 3 medical theses, and 2 diplomas with sev-
eral more ongoing. He is cofounder and Editor-in-Chief of the
first and only online open access biomaterials journal: “Euro-
AODIALOGUE 1 | 07
Fig 4 4-hole LCPs used with locking screws in our current cpTi
(silver), standard microrough cpTi (gold), polished anodized
titanium (blue) and electropolished stainless steel control
(silver).
ble in one anatomical situation, yet not in another. Polishing
is not the answer to everything, though may have use in cer-
tain clinical applications as mentioned within this article.
There is no ‘one surface’ for all applications and surfaces on
one implant interacting with different tissues need to be con-
sidered as separate entities.
R Geoff Richards, Prof Dr Sci
Program Leader Bio-performance of
Materials & Devices
AO Research Institute, Davos, Switzerland
geoff.richards@aofoundation.org
pean Cells & Materials” (www.ecmjournal.org) which has
4,850 registered readers worldwide and is indexed by Medline
among others. Geoff is an honorary Senior Research Fellow at
the University of Glasgow, honorary lecturer at Aberystwyth
University and has a 3 year visiting Professorship at Tokyo
Medical and Dental University, Japan. He is President of the
Swiss Society for Biomaterials and has organised many con-
ferences and symposiums within this field.