1) Tissue reactions to spinal implants can include corrosion, wear, and inflammation due to metal debris. Different implant materials like titanium alloys and stainless steel are susceptible to corrosion. 2) Studies of retrieved spinal implants found wear and corrosion at interfaces between components, as well as metal debris in surrounding tissues sometimes causing inflammation. 3) While titanium is generally considered biocompatible, wear particles have been found to induce cytokine release and osteolysis, potentially impairing spinal fusions. Careful consideration of implant material combinations and interfaces is important.

1. Tissue reactions toTissue reactions to
spinal implantsspinal implants
George SapkasGeorge Sapkas
Asc. ProfessorAsc. Professor
11stst
Orthopaedic Dept.Orthopaedic Dept.
Medical school, Athens UniversityMedical school, Athens University
Metropolitan HospitalMetropolitan Hospital

2. There is a wideThere is a wide
variety of implantvariety of implant
designs including:designs including:
Segmental andSegmental and
non-segmentalnon-segmental
constructsconstructs
Rigid andRigid and
semi-rigidsemi-rigid
connectorsconnectors
Different materialsDifferent materials
and surfaceand surface
treatments.treatments.

3. Spinal implantsSpinal implants
Factors of corrosionFactors of corrosion
1)1) Combination of different metallic materialsCombination of different metallic materials
2)2) Surfaces’ composition and irregularitySurfaces’ composition and irregularity
3)3) Micro-movements between the parts of theMicro-movements between the parts of the
spinal instrumentationspinal instrumentation
4)4) Ions of ClIons of Cl--
from the plasma andfrom the plasma and
intercellular areaintercellular area
5)5) pHpH
6)6) Different concentration of ODifferent concentration of O22 ionsions
in free and covered metallic areasin free and covered metallic areas

4. Metal corrosionMetal corrosion
galvanic corrosion
different metals
fretting corrosion
same metals in micro-movement
crevice corrosion
metals in different electrolytic fluids

5. Galvanic corrosion
different metals
AcceleratedAccelerated decay due to neighboring of dissimilardecay due to neighboring of dissimilar
metallic implants in a corrosivemetallic implants in a corrosive
electrolytic environmentelectrolytic environment
Electrochemical dissimilarityElectrochemical dissimilarity
It is possible to take placeIt is possible to take place
even between the same typeeven between the same type
of materials in different end-plateof materials in different end-plate
surfacessurfaces
It is common in articulated spinal implantsIt is common in articulated spinal implants

6. Fretting corrosionFretting corrosion
same metals in micro-movement

7. Crevice corrosionCrevice corrosion
metals in different electrolytic fluids
OH-
OH-
OH- OH-
O2
O2
O2

8. Approximately theseApproximately these
metalic constructsmetalic constructs
are made of:are made of:
35% stainless steel35% stainless steel
65% (Ti64) alloy65% (Ti64) alloy
titaniumtitanium
aluminium – 6aluminium – 6
vanadium - 4vanadium - 4

9. Mechanical damageMechanical damage
fromfrom frettingfretting
can compromisecan compromise
passivated surfacespassivated surfaces
and result in:and result in:
ionic debrisionic debris fromfrom
corrosioncorrosion
andand
particulate debrisparticulate debris
from mechanicalfrom mechanical
damagedamage..

10. Ionic debrisIonic debris
is additiveis additive
to the influencesto the influences
ofof particulate debrisparticulate debris
andand
can have a significantcan have a significant
impact onimpact on local cytotoxicity.local cytotoxicity.

11. The use of metalThe use of metal
instrumentation,instrumentation,
particularly titanium,particularly titanium,
for spinal fusion has introducedfor spinal fusion has introduced
the possibilitythe possibility
of generatingof generating
microscopic metal particlesmicroscopic metal particles
that may be deposited :that may be deposited :
in the paraspinal soft tissuesin the paraspinal soft tissues
oror
on the neural elements.on the neural elements.

12. In vitro studies haveIn vitro studies have
shown that theseshown that these
metal particles can bemetal particles can be
phagocytizedphagocytized
intracellularlyintracellularly
leadingleading
to release ofto release of
inflammatoryinflammatory
cytokinescytokines
Betts F. et al, Clin Orth., 1992
Lee JM et al, J.B.J.S. 1992

13. ThisThis
inflammatoryinflammatory
cascade maycascade may
lead in turn to:lead in turn to:
resorption ofresorption of
bone andbone and
cellular deathcellular death
Hallab NJ, Cunnigham B et al, Spine 2003

14. The potentialThe potential
forfor bonebone resorptionresorption
is particularlyis particularly
distressingdistressing
in spinal surgeryin spinal surgery
because much of thebecause much of the
operation’s successoperation’s success
depends ondepends on
obtainingobtaining
a spinal fusion.a spinal fusion.

15. The toxic effectsThe toxic effects
of these metalof these metal
particlesparticles
also are of greatalso are of great
concern becauseconcern because
thethe neural elementsneural elements
are widely exposedare widely exposed
during spinalduring spinal
decompressions.decompressions.

16. Few studies on systemicFew studies on systemic
problems suggest thatproblems suggest that
metals disolve, circulate inmetals disolve, circulate in
the body fluid andthe body fluid and
accumulate the remoteaccumulate the remote
organs :organs :
BrainBrain
LungsLungs
LiverLiver
SpleenSpleen
KidneysKidneys
Lymph nodesLymph nodes
etcetc
Coleman RF et al BMJ 1973
Dorr LD et al Clin Orthop 1990
Yuichi Kasai, et al Spine 2003

17. TitaniumTitanium
TitaniumTitanium generally isgenerally is
regarded as safe forregarded as safe for
an organism, but it isan organism, but it is
reported that titaniumreported that titanium
has a biochemicalhas a biochemical
action of increasing:action of increasing:
prostagladin E2prostagladin E2
oror
interleukin 1interleukin 1
Tsustui T., et al, J. Orthop. Science 1999

18. TitaniumTitanium
The wear particles ofThe wear particles of titanium alloytitanium alloy
are less toxic than cobalt-chromiumare less toxic than cobalt-chromium
particles, but more strongly induceparticles, but more strongly induce
inflammation and osteolysis.inflammation and osteolysis.
TitaniumTitanium is known to wear out easily,is known to wear out easily,
and thus may cause localized problemsand thus may cause localized problems
in the tissues surrounding implantsin the tissues surrounding implants
or travel to distant organsor travel to distant organs
and cause systemic problemsand cause systemic problems
Nakagava M et al , Lancet 1973
Krupa D, et al Biomaterials 2001

19. Stainless steelStainless steel
Increased resistant toIncreased resistant to
corrosion with thecorrosion with the
addition :addition :
ChromiumChromium
NikeliumNikelium
MolybdenumMolybdenum

20. Recent researchRecent research
on tissue reactionson tissue reactions
to spinal implantsto spinal implants

21. Metal debris From TitaniumMetal debris From Titanium
Spinal ImplantsSpinal Implants
Wang et al, Spine, 1999Wang et al, Spine, 1999

22. Study Design.
A prospective study of tissue
surrounding spinal
instrumentation was
performed using histologic
and chemical analysis.
Objectives.
identify
quantify
the amount of metal debris
generated by titanium
pedicle screw
instrumentation
evaluate the histologic
response in the spinal
tissues.

23. Conclusions.
Wear debris is generated
by the use of titanium
spinal instrumentation in
patients with a
pseudarthrosis.
These particles activate a
macrophage cellular
response in the spinal
tissues similar to that
seen in surrounding joint
prostheses.
Patients with a solid
spinal fusion have
negligible levels of
particulate matter.

24. Biocompatibility studies of
titanium-based alloy pedicle
screw and
rod system: histological aspects
Kazuhiro Yamaguchi, MD et al, The Spine Journal, 2001

25. Study Design:
Few histological studies of pedicle screw and rod
systems have been done, and spinal surgery with
pedicle screw and rod system is increasing.
Objectives:
To know the biocompatibility of pedicle screw and rod
systems histologically.
Study design/setting:
Titanium-based alloy pedicle screws were removed
from 20 patients. Histological studies of the tissue
response to the screws were performed by light
microscopy.

26. Photograph showing spinal fusion
using the Diapason system.
Histological areas were divided into four
areas.
Area 1, muscle 1 cm posterior from screw.
Area 2, muscle–screw interface.
Area 3, tissue around the screw–rod joints.
Area 4, bone–screw interface.

27. Conclusions:
Titanium-based alloy pedicle screws produced
some metal debris and caused localized
inflammation.
No adverse tissue reaction was observed around
the screws and rods.
Direct contact without any fibrous tissue formation
at the bone–screw interface was observed in some
patients.
A titanium-based alloy pedicle screw and rod
system is considered biocompatible histologically.

28. The effect of spinal
instrumentation particulate wear
debris: an in vivo
rabbit model and applied clinical
study of
retrieved instrumentation cases
Cunningham B. W., et al, The Spine Journal 2003

29. Study design:
The current study was undertaken to determine if:
the presence of spinal instrumentation wear
particulate debris deleteriously influences early
osseointegration of posterolateral bone graft
disrupts an established posterolateral fusion mass.
Objectives:
Using an in vivo animal model,
The first phase (basic science) of this study was to
evaluate the effect(s) of titanium wear particulate on
a posterolateral spinal arthrodesis based on
serological, histological and immunocytochemical
analyses.
The second phase (clinical) was to perform the
same analysis of soft tissue surrounding spinal
instrumentation in 12 symptomatic clinical patients.

30. Conclusions:
– Titanium particulate debris introduced at the level
of a spinal arthrodesis elicit:
a cytokinemediated particulate-induced response
favoring:
proinflammatory infiltrates,
increased expression of intracellular TNF-a,
increased osteoclastic activity and
cellular apoptosis.
This is the first basic scientific study and the first clinical
study demonstrating associations of :
spinal instrumentation particulates wear debris
and increased cytokines
and increased osteoclastic activity.
Osteolysis is the number one cause of failure of
orthopedic implants in the appendicular skeleton.

31. Ultrastructural analysis of metallicUltrastructural analysis of metallic
debris and tissue reaction arounddebris and tissue reaction around
spinal implants in patients with latespinal implants in patients with late
operative site painoperative site pain
(stainless steel implants)(stainless steel implants)
Senaran H., et al, Spine 2004

32. Objective
– to clarify the cause of late operative site pain
by the ultrastructural analysis of the
byproducts of metallic corrosion (stainless
steel) as well as the surrounding soft tissues

33. Results
– No signs of infection were present
– Macrophage counts were most abundant
around pedicular screws when compared to:
around the rods
or around the transverse rod connectors
– Particular debris were more abundant around
the rods and transverse connectors

34. Conclusions
– The reaction to particulate metallic debris
from stainless steel implants may be a
probable cause of
Late Operative Site Pain
– There were not findings suggesting the
presence of infection, although the presence
of low-grade infection could not be ruled out

35. Is galvanic corrosion between
titanium alloy and stainless
steel spinal
implants a clinical concern?
Hassan Serhan, PhD, et al, The Spine Journal 4 (2004)

36. BACKGROUND CONTEXT:
– Surgeons are hesitant to mix components
made of differing metal classes for fear of
galvanic corrosion complications.
– However, in vitro studies have failed to show
a significant potential for galvanic corrosion
between titanium and stainless steel, the two
primary metallic alloys used for spinal
implants.
– Galvanic corrosion resulting from metal
mixing has not been described in the literature
for spinal implant systems.

37. METHODS:
– Each construct was immersed in phosphate-
buffered saline (pH 7.4) at 37 C and tested in
cyclic compression.
– The samples were then removed and
analyzed visually for evidence of corrosion.
– In addition, scanning electron microscopy
(SEM) and energy dispersive spectrometry
(EDS) were used to evaluate the extent of
corrosion at the interconnections.

38. Setup of test construct
according to ASTM
F1717 and evidence of
corrosion at implant
component interfaces.
Two constructs in this
study consisted of
titanium alloy rods and
pedicle screws with
mixed titanium alloy and
stainless steel rod–
screw connectors and
transverse rod connector
components, as shown
with arrows.

39. Setup of test construct
according to ASTM
F1717 and evidence of
corrosion at implant
component interfaces.
Two constructs in this
study consisted of
stainless steel rods and
pedicle screws with
mixed titanium alloy and
stainless steel rod–
screw connectors and
transverse rod connector
components, as shown
with arrows.

40. CONCLUSIONS:
– The results from this study indicate that when
loaded dynamically in saline, stainless steel
implant components have a greater
susceptibility to corrosion than titanium.
– Furthermore, the galvanic potential between
the dissimilar metals does not cause a
discernible effect on the corrosion of either.
– Although the mixture of titanium alloy with
stainless steel is not advocated, the results of
this study suggest that galvanic corrosion is
less pronounced in SS-Ti mixed interfaces
than in all stainless steel constructs.

41. Wear and corrosion inWear and corrosion in
retrieved thoracolumbarretrieved thoracolumbar
posterior internal fixation.posterior internal fixation.
Villarraga M.l., et al, Spine 2007

42. STUDY DESIGNSTUDY DESIGN
Posterior thoracolumbarPosterior thoracolumbar
spine implants retrievedspine implants retrieved
as part of routine clinicalas part of routine clinical
practice over a 2-yearpractice over a 2-year
period wereperiod were analyzed toanalyzed to
identify wear andidentify wear and
corrosion.corrosion.
OBJECTIVEOBJECTIVE
Engineering analyses ofEngineering analyses of
retrieved posteriorretrieved posterior
instrumentation forinstrumentation for
indications of :indications of :
– performance andperformance and
– failure andfailure and
– correlation of thiscorrelation of this
information with clinicalinformation with clinical
factorsfactors

43. CONCLUSIONSCONCLUSIONS
Retrieved rods exhibited:Retrieved rods exhibited:
– corrosion,corrosion,
– wear,wear,
– fracture,fracture,
– with wear and corrosionwith wear and corrosion
mainly located at themainly located at the
interfaces with hooks, screws,interfaces with hooks, screws,
or cross-connectors.or cross-connectors.

44. Electron Microprobe Analysis
and Tissue Reaction around
Titanium Alloy Spinal Implants
Hee-Dong Kim et al, Asian Spine Journal 2007

45. Study Design:
– A retrospective study of tissue surrounding
titanium alloy spinal implants was performed
using histological and electron microprobe
analysis.
Purpose:
– To identify the metal debris generated by
spinal implants, and then to evaluate the
electron microprobe analysis results and the
histological response of soft tissue
surrounding the spinal implants.

46. Results:
– There were metal particles in the soft tissue in 70% of
the cases.
– Histological finding observed mild chronic
inflammation surrounding the deposition of the metal
particles.
– Scanning electron microscopy of the specimens
showed metallic debris within the tissue and mapping
of the metallic particles revealed the distribution of
titanium in the tissue.
– 90% of patients had successful relief of back pain
after removing the spinal implants.
– Improvement of the back pain may be an association
macrophage response rather than the metal particle.

47. (A) Operative finding shows
local discolorization of the soft
tissues around spinal implant
(Case 2).
(B) Histologic finding reveals
obvious metallosis with black
staining of the tissue.
(C) Scanning electron
microscopy view of specimen
shows the metallic debris within
tissue(×1,000) and mapping of
the metallic particles shows the
distributions of the titanium in
the tissue.
(D) Quantitative analysis of the
metallic debris of specimen was
done with energy dispersive X-
ray spectrometer.

48. (A) Metallic debris was
identified in the dense
connective tissue and the
anti Cotrel-Dubousset 68
positive macrophages
were observed at tissue
adjacent to the metal
particles (Avidin-biotin
complex, ×100).
(B) Macrophages as
stained positive by anti
CD 68 marker (Avidin-
biotin complex, ×200,
Case 5).

49. Conclusions:
– The presence of metallic particles generated
from spinal implants may serve as the
impetus for a late-onset inflammatory
response and late operative site pain.

50. BiocompatibilityBiocompatibility
ofof
Dynesys ImplantsDynesys Implants
Prof H.G Willert, Cottingen Germany

52. The mobile construct always was encapsulated by a demarcation membrane with a
definite synovial lining.

53. The bone at the base of the transverse process
as it is rubing against the elastic and moving polycarbonate – urethan spacer – sleeve
was covered with organised, multilayered cartilage
that must have formed by some type of periosteal metaplasia

54. Another favourable observation was
the complete absence of cellular reaction to the PET cord
as well as the virtual absence of particle abrasion
and giant cell i.e. phagocyte reaction.

55. The biologic response toThe biologic response to
particles from a lumbar discparticles from a lumbar disc
prosthesisprosthesis
Moore R.J., et al, Spine 2002

56. Study designStudy design
Particles of a propriety polyolefinParticles of a propriety polyolefin
rubber compoundrubber compound used in aused in a
lumbar disc prosthesis werelumbar disc prosthesis were
generated in vitro and tested forgenerated in vitro and tested for
biocompatibility in two animalbiocompatibility in two animal
modelsmodels
ObjectiveObjective
To characterize any tissueTo characterize any tissue
response to polyolefin rubberresponse to polyolefin rubber
particlesparticles
MethodMethod
Laboratory generated polyolefinLaboratory generated polyolefin
rubber particles were either:rubber particles were either:
injected into dorsalinjected into dorsal subcutaneoussubcutaneous
air pouches ofair pouches of 30 rats30 rats
or placed directly onto theor placed directly onto the
lumbosacrallumbosacral dura and nerve rootsdura and nerve roots
of 9 sheep.of 9 sheep.
Transmission electron photomicrograph
of one batch polyolefin rubber particles
prepared in vitro

57. ConclusionConclusion
The polyolefin rubberThe polyolefin rubber
particles induceparticles induce onlyonly
localized tissuelocalized tissue
responseresponse that isthat is
consistent with aconsistent with a
normal foreign bodynormal foreign body
reaction to largereaction to large
notoxic particles.notoxic particles.
Dura (arrow) surrounding the
spinal cord at S2 of a sheep
3 months after application of
polyolefin rubber particles.
There is focal thickening of the dura
by reactive fibro – adipose tissue

58. Basic scientificBasic scientific
considerations in total discconsiderations in total disc
arthroplastyarthroplasty
Cunningham BW, Spine Journal 2004.

59. BACKGROUNDBACKGROUND
CONTEXT:CONTEXT:
Total disc arthroplastyTotal disc arthroplasty
serves as the nextserves as the next
frontier in the surgicalfrontier in the surgical
management ofmanagement of
intervertebralintervertebral
discogenic pathology.discogenic pathology.

60. PURPOSE:PURPOSE:
As we move from an era of interbodyAs we move from an era of interbody
spinal arthrodesis to one in whichspinal arthrodesis to one in which
segmental motion is preserved, thissegmental motion is preserved, this
promising new technology offerspromising new technology offers
increasing clinical and researchincreasing clinical and research
challenges in the areas of spinalchallenges in the areas of spinal
kinematics:kinematics:
a.a. histologic osseointegration at thehistologic osseointegration at the
prosthetic-bone interfaceprosthetic-bone interface
andand
b.b. the effects of particulate wear debris.the effects of particulate wear debris.
STUDY DESIGN:STUDY DESIGN:
The primary focus of this paper is toThe primary focus of this paper is to
provide a methodologic basis toprovide a methodologic basis to
investigate :investigate :
a.a. the spinal kinematics,the spinal kinematics,
b.b. histologic osseointegration andhistologic osseointegration and
c.c. particulate wear debris after total discparticulate wear debris after total disc
arthroplastyarthroplasty
by using in vitro and in vivo models.by using in vitro and in vivo models.

61. METHODS:METHODS:
Using an in vitro cadavericUsing an in vitro cadaveric
model, multidirectionalmodel, multidirectional
flexibility testing evaluatedflexibility testing evaluated
the functional unitthe functional unit
kinematics under thekinematics under the
following L4-L5following L4-L5
reconstruction conditions:reconstruction conditions:
1) intact spine,1) intact spine,
2) Charite disc prosthesis,2) Charite disc prosthesis,
3) BAK cages,3) BAK cages,
4) BAK cages+ISOLA pedicle4) BAK cages+ISOLA pedicle
screw or rod fixationscrew or rod fixation
(anteroposterior).(anteroposterior).

62. RESULTSRESULTS
Direct epidural application of spinal instrumentationDirect epidural application of spinal instrumentation
particulate wear debrisparticulate wear debris
elicits:elicits:
a chronic histiocytic reactiona chronic histiocytic reaction
localized primarily withinlocalized primarily within
the epidural fibrous layers.the epidural fibrous layers.
Moreover,Moreover, particles have the capacity to diffuseparticles have the capacity to diffuse
intrathecallyintrathecally, eliciting a macrophage and cytokine, eliciting a macrophage and cytokine
response within:response within:
the epidural tissues,the epidural tissues,
cerebrospinal fluidcerebrospinal fluid
and spinal cord itself.and spinal cord itself.
Overall, on the basis of the postoperativeOverall, on the basis of the postoperative
time periods evaluated,time periods evaluated,
no evidence was observed of an acute neural orno evidence was observed of an acute neural or
systemic histopathologic response to the materialssystemic histopathologic response to the materials
included in the current project.included in the current project.

63. ConclusionsConclusions

64. With the introduction of
modular artificial disc
replacements and
new materials for
orthopedic spinal
implants,
the effects of implant-
fretting corrosion on
local spinal and
systemic tissues
will remain a clinical
concern.

65. The presence of
titanium particulate
debris, secondary to
motion between spinal
implants, may serve
as:
the impetus for
late-onset
inflammatory-
infectious
complications
and
long-term osteolysis
of an established
posterolateral fusion
mass in the clinical
setting.

66. University Hospital “ATTIKON”