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Tissue reactions Tissue reactions to spinal to spinal implants implants George Sapkas George Sapkas Asc. Professor Asc. Professor 1 1 st st Orthopaedic Dept. Orthopaedic Dept. Medical school, Athens University Medical school, Athens University Metropolitan Hospital Metropolitan Hospital

Tissue Reaction

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Page 1: Tissue Reaction

Tissue reactions to Tissue reactions to spinal implantsspinal implants

George SapkasGeorge Sapkas

Asc. ProfessorAsc. Professor11stst Orthopaedic Dept. Orthopaedic Dept.

Medical school, Athens UniversityMedical school, Athens UniversityMetropolitan HospitalMetropolitan Hospital

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There is a wide There is a wide variety of implant variety of implant designs including:designs including:

Segmental and Segmental and non-segmental non-segmental constructsconstructsRigid and Rigid and semi-rigid semi-rigid connectorsconnectorsDifferent materials Different materials and surface and surface treatments.treatments.

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Spinal implantsSpinal implants

Factors of corrosion Factors of corrosion

1) 1) Combination of different metallic materialsCombination of different metallic materials2) 2) Surfaces’ composition and irregularitySurfaces’ composition and irregularity 3) 3) Micro-movements between the parts of the Micro-movements between the parts of the

spinal instrumentation spinal instrumentation 4) 4) Ions of ClIons of Cl-- from the plasma and from the plasma and

intercellular areaintercellular area5) 5) pHpH6) 6) Different concentration of ODifferent concentration of O22 ions ions

in free and covered metallic areasin free and covered metallic areas

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Metal corrosionMetal corrosion galvanic corrosion

different metals

fretting corrosion

same metals in micro-movement

crevice corrosion

metals in different electrolytic fluids

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Galvanic corrosion different metals

Accelerated Accelerated decay due to neighboring of dissimilar decay due to neighboring of dissimilar metallic implants in a corrosivemetallic implants in a corrosiveelectrolytic environmentelectrolytic environmentElectrochemical dissimilarity Electrochemical dissimilarity

It is possible to take placeIt is possible to take placeeven between the same typeeven between the same typeof materials in different end-plate of materials in different end-plate surfacessurfaces

It is common in articulated spinal implantsIt is common in articulated spinal implants

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Fretting corrosionFretting corrosion same metals in micro-movement

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Crevice corrosionCrevice corrosionmetals in different electrolytic fluids

OH-

OH-

OH- OH-

O2

O2

O2

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Approximately these Approximately these metalic constructs metalic constructs are made of:are made of:

35% stainless steel35% stainless steel

65% (Ti64) alloy 65% (Ti64) alloy titaniumtitanium

aluminium – 6aluminium – 6

vanadium - 4vanadium - 4

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Mechanical damage Mechanical damage from from frettingfretting can compromise can compromise passivated surfaces passivated surfaces and result in:and result in:

ionic debrisionic debris from from corrosion corrosion and and

particulate debris particulate debris from mechanical from mechanical damagedamage..

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Ionic debrisIonic debris is additive is additive to the influences to the influences of of particulate debrisparticulate debris and and can have a significant can have a significant impact on impact on local cytotoxicity.local cytotoxicity.

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The use of metal The use of metal instrumentation, instrumentation, particularly titanium,particularly titanium, for spinal fusion has introduced for spinal fusion has introduced the possibility the possibility of generating of generating microscopic metal particles microscopic metal particles that may be deposited :that may be deposited :

in the paraspinal soft tissues in the paraspinal soft tissues

or or

on the neural elements.on the neural elements.

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In vitro studies have In vitro studies have shown that these shown that these metal particles can be metal particles can be phagocytizedphagocytized intracellularlyintracellularly leading leading to release of to release of inflammatory inflammatory cytokinescytokines

Betts F. et al, Clin Orth., 1992Lee JM et al, J.B.J.S. 1992

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This This inflammatory inflammatory cascade may cascade may lead in turn to: lead in turn to:

resorption of resorption of bone and bone and

cellular deathcellular death

Hallab NJ, Cunnigham B et al, Spine 2003

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The potential The potential for for bonebone resorptionresorption is particularly is particularly distressing distressing in spinal surgery in spinal surgery because much of the because much of the operation’s success operation’s success depends on depends on obtaining obtaining a spinal fusion.a spinal fusion.

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The toxic effects The toxic effects of these metal of these metal particles particles also are of great also are of great concern because concern because the the neural elementsneural elements are widely exposed are widely exposed during spinal during spinal decompressions.decompressions.

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Few studies on systemic Few studies on systemic problems suggest that problems suggest that metals disolve, circulate in metals disolve, circulate in the body fluid and the body fluid and accumulate the remote accumulate the remote organs :organs :

BrainBrain

LungsLungs

LiverLiver

SpleenSpleen

KidneysKidneys

Lymph nodesLymph nodes

etcetc

Coleman RF et al BMJ 1973Dorr LD et al Clin Orthop 1990Yuichi Kasai, et al Spine 2003

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TitaniumTitanium

TitaniumTitanium generally is generally is regarded as safe for regarded as safe for an organism, but it is an organism, but it is reported that titanium reported that titanium has a biochemical has a biochemical action of increasing: action of increasing:

prostagladin E2 prostagladin E2 or or

interleukin 1interleukin 1

Tsustui T., et al, J. Orthop. Science 1999

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TitaniumTitaniumThe wear particles of The wear particles of titanium alloytitanium alloy are less toxic than cobalt-chromium are less toxic than cobalt-chromium particles, but more strongly induce particles, 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 problems and thus may cause localized problems

in the tissues surrounding implants in the tissues surrounding implants or travel to distant organs or travel to distant organs and cause systemic problemsand cause systemic problems

Nakagava M et al , Lancet 1973Krupa D, et al Biomaterials 2001

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Stainless steelStainless steel

Increased resistant to Increased resistant to corrosion with the corrosion with the addition :addition :

Chromium Chromium

NikeliumNikelium

Molybdenum Molybdenum

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Recent research Recent research on tissue reactionson tissue reactions to spinal implants to spinal implants

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Metal debris From Titanium Metal debris From Titanium Spinal ImplantsSpinal Implants

Wang et al, Spine, 1999Wang et al, Spine, 1999

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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 instrumentationevaluate the histologic response in the spinal tissues.

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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.

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Biocompatibility studies of titanium-based alloy pedicle

screw androd system: histological aspects

Kazuhiro Yamaguchi, MD et al, The Spine Journal, 2001

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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.

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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.

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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.

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The effect of spinal instrumentation particulate wear

debris: an in vivorabbit model and applied clinical

study ofretrieved instrumentation cases

Cunningham B. W., et al, The Spine Journal 2003

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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.

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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.

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Ultrastructural analysis of metallic Ultrastructural analysis of metallic debris and tissue reaction around debris and tissue reaction around

spinal implants in patients with late spinal implants in patients with late operative site painoperative site pain

(stainless steel implants)(stainless steel implants)

Senaran H., et al, Spine 2004

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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

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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

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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

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Is galvanic corrosion between titanium alloy and stainless

steel spinalimplants a clinical concern?

Hassan Serhan, PhD, et al, The Spine Journal 4 (2004)

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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.

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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.

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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.

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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.

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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.

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Wear and corrosion in Wear and corrosion in retrieved thoracolumbar retrieved thoracolumbar

posterior internal fixation.posterior internal fixation.

Villarraga M.l., et al, Spine 2007

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STUDY DESIGNSTUDY DESIGN

Posterior thoracolumbar Posterior thoracolumbar spine implants retrieved spine implants retrieved as part of routine clinical as part of routine clinical practice over a 2-year practice over a 2-year period were period were analyzed to analyzed to identify wear and identify wear and corrosion. corrosion.

OBJECTIVEOBJECTIVEEngineering analyses of Engineering analyses of retrieved posterior retrieved posterior instrumentation for instrumentation for indications of : indications of :

– performance and performance and – failure and failure and – correlation of this correlation of this

information with clinical information with clinical factorsfactors

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CONCLUSIONSCONCLUSIONS

Retrieved rods exhibited:Retrieved rods exhibited:– corrosion, corrosion, – wear, wear, – fracture,fracture, – with wear and corrosion with wear and corrosion

mainly located at the mainly located at the interfaces with hooks, screws, interfaces with hooks, screws, or cross-connectors. or cross-connectors.

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Electron Microprobe Analysis and Tissue Reaction around

Titanium Alloy Spinal Implants

Hee-Dong Kim et al, Asian Spine Journal 2007

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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.

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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.

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(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.

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(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).

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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.

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Biocompatibility Biocompatibility of of

Dynesys ImplantsDynesys Implants

Prof H.G Willert, Cottingen Germany

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

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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

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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.

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The biologic response to The biologic response to particles from a lumbar disc particles from a lumbar disc

prosthesisprosthesis

Moore R.J., et al, Spine 2002

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Study designStudy design

Particles of a propriety polyolefin Particles of a propriety polyolefin rubber compoundrubber compound used in a used in a lumbar disc prosthesis were lumbar disc prosthesis were generated in vitro and tested for generated in vitro and tested for biocompatibility in two animal biocompatibility in two animal modelsmodels

Objective Objective To characterize any tissue To characterize any tissue response to polyolefin rubber response to polyolefin rubber particlesparticles

MethodMethodLaboratory generated polyolefin Laboratory generated polyolefin rubber particles were either:rubber particles were either:injected into dorsal injected into dorsal subcutaneous subcutaneous air pouches ofair pouches of 30 rats30 rats or placed directly onto the or placed directly onto the lumbosacral lumbosacral dura and nerve roots dura and nerve roots of 9 sheep. of 9 sheep.

Transmission electron photomicrograph of one batch polyolefin rubber particles prepared in vitro

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ConclusionConclusion

The polyolefin rubber The polyolefin rubber particles induce particles induce only only localized tissue localized tissue responseresponse that is that is consistent with a consistent with a normal foreign body normal foreign body reaction to large reaction 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 duraby reactive fibro – adipose tissue

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Basic scientific Basic scientific considerations in total disc considerations in total disc

arthroplastyarthroplasty

Cunningham BW, Spine Journal 2004.

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BACKGROUND BACKGROUND CONTEXT: CONTEXT:

Total disc arthroplastyTotal disc arthroplasty serves as the next serves as the next frontier in the surgical frontier in the surgical management of management of intervertebral intervertebral discogenic pathology. discogenic pathology.

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PURPOSE: PURPOSE:

As we move from an era of interbody As we move from an era of interbody spinal arthrodesis to one in which spinal arthrodesis to one in which segmental motion is preserved, this segmental motion is preserved, this promising new technology offers promising new technology offers increasing clinical and research increasing clinical and research challenges in the areas of spinal challenges in the areas of spinal kinematics:kinematics:a.a. histologic osseointegration at the histologic osseointegration at the

prosthetic-bone interface prosthetic-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 to The primary focus of this paper is to provide a methodologic basis to provide a methodologic basis to investigate :investigate :a.a. the spinal kinematics, the spinal kinematics,

b.b. histologic osseointegration and histologic osseointegration and

c.c. particulate wear debris after total disc particulate wear debris after total disc arthroplastyarthroplasty by using in vitro and in vivo models. by using in vitro and in vivo models.

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METHODS: METHODS: Using an in vitro cadaveric Using an in vitro cadaveric model, multidirectional model, multidirectional flexibility testing evaluated flexibility testing evaluated the functional unit the functional unit kinematics under the kinematics under the following L4-L5 following 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 pedicle 4) BAK cages+ISOLA pedicle screw or rod fixation screw or rod fixation (anteroposterior). (anteroposterior).

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RESULTSRESULTS

Direct epidural application of spinal instrumentation Direct epidural application of spinal instrumentation particulate wear debrisparticulate wear debris elicits:elicits:

a chronic histiocytic reaction a chronic histiocytic reaction localized primarily within localized primarily within the epidural fibrous layers. the epidural fibrous layers.

Moreover, Moreover, particles have the capacity to diffuse particles 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 fluid cerebrospinal fluid and spinal cord itself. and spinal cord itself.

Overall, on the basis of the postoperative Overall, on the basis of the postoperative time periods evaluated, time periods evaluated, no evidence was observed of an acute neural or no 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.

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Conclusions Conclusions

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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.

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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.

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University Hospital “ATTIKON”