Metal vs PEEK: Material ConsiderationsTitanium Coating in vitro Evaluation Assays: o Cell Adhesion/Proliferation Assay: Cells seeded onto tissue culture plastic or disc substrates

Metal vs PEEK:Material Considerations

Calusa Ambulatory Spine ConferenceNovember 12, 2016Boyle C. Cheng, PhD

Disclosure

• Research Funding

• Aesculap

• Alphatec Spine

• Globus

• K2M

• Medtronic

• OrthoKinematics

• Ratchiotek

• SI-Bone

• Stryker Spine

Healthcare Providers

Election Year

• Step 1: Cut out ear slots• Step 2: Cut out deflector• Step 3: Place over earlobes

Anterior Column Support:Devices Bone Implant Interface

Courtesy: Scott Webb

WALKER, JASON - 2/23/2012 15:27; !S_72110Spine - Lumbar 4V

Image Page 1

WALKER, JASON - 960606864DOB: 8/13/1973 038YExam: !S_721102/23/2012

Fondren Orthopedic Group,LLPAcquired: S

TECH, *2/23/2012 3:28:48 PM

Laterality: U

Ser 2(1) Img 11972 x 2414 x 12

Zoom: 5.2:1True Size: 65%W 4095 L 2047W 4095 L 2047Compress: 2:1

Plain Film X-Rays of PEEK Interbody Implants

Titanium

Screws

Titanium

Screws

Sheep #3987mm cTDR @ 6mos.

Device Failure

Migration and Expulsion

Moatz B and Tortolani, Cervical disc arthroplasty: Pros and consJ Surg Neurol Int 2012, 3:216

Government Accountability Office: January 2009

• FDA submission through the 510(k) process between 2003-2007• Class I and II devices, 13,199

submissions (90% cleared)• Class III devices, 342

submissions were submitted with only 228 cleared (67%)

• For class III PMA submissions, 217 original and 784 supplemental, 78% and 85%, respectively, were approved

Ti Surfaces

Additive Manufacturing

Dental Implant Screw

3D Printing - not just for

plastics, can also print implantable

metal materials (e.g. CoCr &

Ti6Al4V).

Successive layers of materials

are laid down under computer

control.

Can be almost any shape or

geometry.

Porosity / open structure ideal

for boney apposition.

Competitive Interbody Products

Biomechanical Goal of the Bone Implant Interface

• Clinical relevance– Reduce instability of

pathologic FSU (< ROM)

• Interface design rational– Provides immediate

stabilization and fixation

– Allows device to perform as intended

• Metric– Interface

– Pullout strength

Bone Implant Interface

Biomechanical Testing:Pullout Strength

Good Idea?

Essential Components of Arthrodesis

• Ti

• PEEK

• collagen

• osteoblasts

• osteoclasts

• BMP’s

• PDGF

Matrix Cells

GrowthFactors

Titanium vs. PEEK: in vitro Evaluation

Objective: Evaluate the effect of the titanium coating on the in vitro adhesion, proliferation and

differentiation of bone-forming cells as compared to non-coated PEEK surfaces.

Substrates: Tissue culture plastic Titanium PEEK

Cells: Human MG-63 osteoblast-like osteosarcoma cells. 15mm diameter discs,10,000 cell/cm2.

Titanium Coating in vitro EvaluationAssays:

o Cell Adhesion/Proliferation Assay: Cells seeded onto tissue culture plastic or disc substrates in 24

well plates in complete media containing serum at 37° C, 5% CO2 until confluent (n=12 per

surface).

o Cell Differentiation Assays: Transcriptional and translational analyses

• Alkaline Phosphatase (ALP) activity, chromogenic assay.

• qRT-PCR Analysis: osteoblast differentiation genes including

type I collagen, osteocalcin, ALP, BSP, BMP-2.

• ELISAs: Secreted bone morphogenetic proteins (BMP-2, BMP-

4, BMP-7)

Rationale: Tracking 3 distinct phases of osteoblast maturation

Growth (proliferation):BMP’s

Extracellular matrix development:ALP, Type I Collagen

Mineralization:Osteocalcin

Cell Activity on Titanium Substrate

80.00

85.00

90.00

95.00

100.00

Average Cell Viability

0.00E+00

5.00E+04

1.00E+05

1.50E+05

2.00E+05

2.50E+05

Cell Y

ield

Average Cell Yield C

ell V

iab

ilit

y

o Lower cell proliferation/growth on Ti

o Consistent with higher level of

differentiation on Ti

o Differentiating cells divide slower

o High cell viability on all surfaces

TC Plastic Titainum PEEK

Cell Activity on Titanium Coated Implants

0.00E+00

5.00E-04

1.00E-03

1.50E-03

2.00E-03

2.50E-03

AL

P

(ng

/µg

pro

tein

)

Surface

Average Alkaline Phosphatase Activity

*

* p

Cell Activity on Rough Titanium

Surfaceso Similar results published for roughened titanium surface (acid etched)

compared to smooth titanium or PEEK.

Taken from: Olivares-Navarette et al., The Spine Journal 12 (2012): 265–272.

Study Design

1. Ovine Model2. Paired Comparison Femora

Implantation1. Treated (Right)2. Control (Left)

3. Implantation1. Survival 12wks (n=5)2. Survival 24wks (n=5)

4. Endpoints1. Local Tissue Tolerance –

Histology2. Bone Implant Interface –

Mechanical Pullout Test

Implantation*Note Consistent Inteference Fit

*Implant specific reamer

Histology:Bony Apposition (0.1mm)

Coated

Uncoated

Histology:New Bone Formation

Stained Histologic Section Analysis of Void

Representative Pull Out Study

Bony Apposition

• Histologic confirmed bone apposition (bone within 0.1mm of surface)

– Statistically significant greater at 12wks

• Good immediate stabilization

New Bone Formation

• New Bone Formation in Surgical Site– New Bone is

statistically significantly greaterat 24wks

• Increased bony ingrowth

Biomechanics

• Pullout strength significantly greater at 12 and 24wk time points compared to uncoated

• Pullout strength greater compared to initial post op condition

Confocal Microscopy

Plasmapore XP (24wk ovine specimen)

Red: New BoneBlue: Collagenand MatrixGold: Plasmapore

Patient 10mos Post-op

Failure Is Not Uncommon

Conclusions

• Bone implant interface may dictate the outcome of the device and subsequently the procedure

• Ti coating may increase short term (friction) and long term stability (bony ingrowth and ongrowth) of the FSU

• Fixation and motion preservation devices benefit from strong bone implant interfaces in the interbody space

Thank you!

Sheep #3966mm cTDR @ 6 mos.

Surgical Grade Materials

Light alloys (Al-alloys.) Parts for Instruments und Devices,

Containers, Motors

Precious Metals (Ag, Au) Probes, Canulas

Nickel alloys Components for MIS-tube instruments

Vacuum cast-Stellite Parts for HM- scissors, Co-Basis + Cr, W,

C, Ta, Mn, Fe min 60 HRC hardness

Ceramics Al2O3 / ZrO2 used for HF-Surgery

Non Ferrous Metals, Special Alloys, Ceramics

Polymers used in Medical Devices

Polymers

Thermoplastics (PE; PEEK, PTFE; PVC; POM; PMMA; PP; …)

Elastomers Thermosetting

(Si Rubber, NBR; …) Thermoplastic

(SEBS; TPU; NBR/PP…)

Metals

Orthopaedic & Spine Implants

Pure Titanium

Titanium Alloys

Stainless Steel

CoCr- Alloys

Tantalum

Nitinol

Complex Geometries for Machining

Polymers

UHMW Polyethylene

PEEK

PMMA

Polyurethane Carbonate

Hydrogels

Silicone

Polyhydroxy Acids

Orthopaedic & Spine Implants

Anterior Column Interbody Device w/

Integrated Supplemental Fixation

The Same Old Story…

• Designer meets technology

• They fall in love

• Many new products designed with new technology• e.g., early 20th century,

radium was a new technology

• Discovered by Madam and Pierre Curie in 1898

Products Designed w/ Radium

Materials Technology: Design Factors

Component Design Changes

• Rigid Devices

– Cage Thickness Changes

– Corpectomy to Interbody Shift

• Material Choices

– Titanium CP

– Titanium Alloy

– Allograft

– Polyetheretherkeytone (PEEK)

Construct Design Philosophy Changes

• Compliant Mechanisms– Charite

– Activ L

• Combined Mechanisms– FSU

Surface Material Technology

Essential Components of Arthrodesis

• Ti

• PEEK

• collagen

• osteoblasts

• osteoclasts

• BMP’s

• PDGF

Matrix Cells

GrowthFactors

Titanium vs. PEEK: in vitro Evaluation

Objective: Evaluate the effect of the titanium coating on the in vitro adhesion, proliferation and

differentiation of bone-forming cells as compared to non-coated PEEK surfaces.

Substrates: Tissue culture plastic Titanium PEEK

Cells: Human MG-63 osteoblast-like osteosarcoma cells. 15mm diameter discs,10,000 cell/cm2.

Titanium Coating in vitro EvaluationAssays:

o Cell Adhesion/Proliferation Assay: Cells seeded onto tissue culture plastic or disc substrates in 24

well plates in complete media containing serum at 37° C, 5% CO2 until confluent (n=12 per

surface).

o Cell Differentiation Assays: Transcriptional and translational analyses

• Alkaline Phosphatase (ALP) activity, chromogenic assay.

• qRT-PCR Analysis: osteoblast differentiation genes including

type I collagen, osteocalcin, ALP, BSP, BMP-2.

• ELISAs: Secreted bone morphogenetic proteins (BMP-2, BMP-

4, BMP-7)

Rationale: Tracking 3 distinct phases of osteoblast maturation

Growth (proliferation):BMP’s

Extracellular matrix development:ALP, Type I Collagen

Mineralization:Osteocalcin

Cell Activity on Titanium Substrate

80.00

85.00

90.00

95.00

100.00

Average Cell Viability

0.00E+00

5.00E+04

1.00E+05

1.50E+05

2.00E+05

2.50E+05

Cell Y

ield

Average Cell Yield C

ell V

iab

ilit

y

o Lower cell proliferation/growth on Ti

o Consistent with higher level of

differentiation on Ti

o Differentiating cells divide slower

o High cell viability on all surfaces

TC Plastic Titainum PEEK

Cell Activity on Titanium Coated Implants

0.00E+00

5.00E-04

1.00E-03

1.50E-03

2.00E-03

2.50E-03

AL

P

(ng

/µg

pro

tein

)

Surface

Average Alkaline Phosphatase Activity

*

* p

Cell Activity on Rough Titanium

Surfaceso Similar results published for roughened titanium surface (acid etched)

compared to smooth titanium or PEEK.

Taken from: Olivares-Navarette et al., The Spine Journal 12 (2012): 265–272.

Cell-Biomaterial Interaction:

Harnessing the power

Spiro| Biologics

Medical Device Surface Modification Technology

Design Iteration: Utilizing a Hybrid Material Design

• Patients

• Surgeon recognized need

• Manufacturer

• Coating expertise

• Regulatory Agency

• FDA

Other Radium Based Products

Failure Ti Coated PEEK

• Material Considerations• PEEK is radiolucent

• PEEK is also less stiff and thus, decreases risk of subsidence

• Ti is stiffer

• Ti makes for excellent bone implant interface

• Additional consideration for hybrid designs

Additional Research: in vivo AND biomechanical studies

in vivo Animal Study Biomechanical Studies

Biomechanics



CautionNuclear Medicine:Chemotherapeutic Agent

Suppository

Conclusions

• Different material substrates illicit different

cellular responses

• Bone implant interface may dictate the

success of the device and subsequently

the procedure.

• Designs that incorporate different

materials may impact clinical outcomes

Thank you!

Axial Pullout Strength of a Plasmapore XP Coated PEEK Implants in Sheep: A Comparative Biomechanical Survival Study

Aesculap Spine DaysMarch 2, 2014

Boyle C. Cheng, PhD

Disclosure

• Research Funding

• Aesculap

• Alphatec Spine

• Globus

• Medtronic

• OrthoKinematics

• Rachiotek

• Stryker Spine

Co-Authors

• D. Cook

• A. Flintrop

• D. Lemesh

• C. Winiarski

• H. Aberman

• C. Wing

• B. Spiro

Many New Technological Advances

Devices Dependent upon the Bone Implant Interface

Courtesy: Scott Webb

Device Failure

Migration and Expulsion

Moatz B and Tortolani, Cervical disc arthroplasty: Pros and consJ Surg Neurol Int 2012, 3:216

Ti Coating: Plasmapore

Biomechanical Goal of the Bone Implant Interface

• Clinical relevance– Reduce instability of

pathologic FSU (< ROM)

• Interface design rational– Provides immediate

stabilization and fixation

– Allows device to perform as intended

• Metric– Interface

– Pullout strength

Bone Implant Interface

Biomechanical Testing:Pullout Strength

Good Idea?

Study Design

1. Ovine Model2. Paired Comparison Femora

Implantation1. Treated (Right)2. Control (Left)

3. Implantation1. Survival 12wks (n=5)2. Survival 24wks (n=5)

4. Endpoints1. Local Tissue Tolerance –

Histology2. Bone Implant Interface –

Mechanical Pullout Test

Implantation*Note Consistent Inteference Fit

*Implant specific reamer

Representative Pull Out Study

Histology:Bony Apposition (0.1mm)

Coated

Uncoated

Bony Apposition

• Histologic confirmed bone apposition (bone within 0.1mm of surface)

– Statistically significant greater at 12wks

• Good immediate stabilization

New Bone Formation

• New Bone Formation in Surgical Site– New Bone is

statistically significantly greaterat 24wks

• Increased bony ingrowth

Biomechanics



Confocal Microscopy

Plasmapore XP (24wk ovine specimen)

Red: New BoneBlue: Collagenand MatrixGold: Plasmapore

Patient 10mos Post-op

Anterior Column Interbody Device w/

Integrated Supplemental Fixation

Conclusions

• Bone implant interface may dictate the outcome of the

device and subsequently the procedure

• Ti coating may increase short term (friction) and long

term stability (bony ingrowth and ongrowth) of the FSU

• Fixation and motion preservation devices benefit from

strong bone implant interfaces in the interbody space

Thank you!

Foundation for Bony Ongrowth and Ingrowth: Mechanotransduction

• CaSO4

• CaPO4

• collagen

• osteoblasts

• marrow

• periosteum

• BMP’s

• PDGF

Matrix Cells

GrowthFactors

Essential Components for Mechanotransduction

Too Much Complex Math…

Performance Metrics (2011)


• Gary Hart (Gary Warren Hartpence)• Senator from CO

• 1975-1987

• 1988 Democratic Party Presidential Nominee

• 20 pt lead prior to picture

• ‘Monkey Business’

Documents

Metal vs PEEK: Material ConsiderationsTitanium Coating in vitro Evaluation Assays: o Cell Adhesion/Proliferation Assay: Cells seeded onto tissue culture plastic or disc substrates