Biomedical€¦ · Biomedical 21st CENTURY ENABLING TECHNOLOGIES 3D Printed PEKK Polymer: Enabling a Family of Medical Devices that Inhibit Bacterial Growth without the Use of Antibiotics

Biomedical

21st CENTURYENABLING TECHNOLOGIES

3D Printed PEKK Polymer: Enabling a Family of Medical Devices that Inhibit Bacterial Growth without the Use of Antibiotics

OXFORD PERFORMANCE MATERIALS, INC – PROPRIETARY AND CONFIDENTIAL

©2020 Oxford Performance Materials, Inc.

The Company


Oxford Performance Materials, Inc.• Founded in 2000• PEKK Technology Focus• Medical Device OEM & CMO• ISO 13485:2016 Certified• FDA Registered• Headquarters in South Windsor, CT, USA

Asia Subsidiary in Japan

• 34,000 sq. ft. Facility in CT Design 3D Printing Extrusion Molding


*OsteoFab® Patient Specific Cranial and Facial Devices distributed worldwide by Zimmer Biomet

OPM was the first company to receive FDA clearance for 3D printed polymer implants


Our 3D Printed Implants Today

OsteoFab® Patient Specific Cranial Device*

OsteoFab® Patient Specific Facial Device*

SpineFab® Vertebral Body Replacement

OsteoFab® Suture Anchor System

(510(k) K133809, K161052)(510(k) K121818, K180064) (510(k) K142005) (510(k) K190915)

PEKK Polymer



PEKK Polymer

PEKK• Increasing

temperature, tolerance, & physical performance

High Performance• Medical• Aerospace• Defense• High Temperature Industrial• Oil Field/Down Hole• High Performance Automotive

Engineering• Sporting Goods• Orthotic/Prosthetic• General Industrial• Lawn & Garden

Commodity• Infrastructure• Packaging

PEKK has exceptional physical properties:

• Superior strength• Excellent chemical

resistance• Tailored electrical

properties• -300°F to 300°F

applications

PEKK Polymer: Biocompatibility• PEKK polymer is shown to be safe for long term human

implantation in sites with primary bone/tissue contact • Extensive testing in accordance with ISO 10993 standards*

Genotoxicity(ISO 10993-3)

Cytotoxicity & Neurotoxicity(ISO 10993-5)

Implantation(ISO 10993-6)

Irritation and Sensitization

(ISO 10993-10)

Systemic Toxicity(ISO 10993-11)

Chemical Characterization(ISO 10993-18)

* Data available in OPM Master FileOXFORD PERFORMANCE MATERIALS, INC – PROPRIETARY AND CONFIDENTIAL

PEKK Polymer: Wettability

Adhesion & Wetting PEKK chemistry highly suitable for bonding Ability to adhere to itself Enabling mechanical performance


3D Printing with PEKK:OsteoFab® Technology



OsteoFab® 3D Printing Manufacturing:Laser Sintering (Laser Melting)

Selective laser sinteringDigital build preparation “Debulking” of implant from powder bed

Dimensional inspectionShipment to healthcare facility


Multiple units processed

in one build

Surgery

OsteoFab® 3D Printing Manufacturing:Laser Sintering (Laser Melting)


• PEKK devices manufactured using OsteoFab® technology have an inherently rough surface

• Peak-and-pit topography contains nano-rough surface characteristics

• Device still solid and non-porous

• Enables important functional properties: bone ongrowth and antibacterial characteristics

OsteoFab® surface structure

Cross section of a typical cranial implant

OsteoFab Technology: Surface Properties

OsteoFab® Surface Properties:Bone Ongrowth


PEEK

OsteoFab®

8 Weeks 12 WeeksBone tissue stained in “purple/red”

Non-bone tissue remained blue


No evidence of bone ongrowth with PEEK

Strong evidence of bone ongrowth with PEKK

Images represent typical results.

Osseointegration of PEKK: Animal Studies

In an ovine model, histological review of OsteoFab 3D Technology samples showed deeper implant osseointegration and more notable trabecular bone ingrowth compared to PEEK and titanium (Ti) coated PEEK.2

(*) TETRAfuse is the trademark of RTI Surgical, Inc. for its use of OPM’s OsteoFab® Technology.

All data above are the property of RTI Surgical, Inc.OXFORD PERFORMANCE MATERIALS, INC – PROPRIETARY AND CONFIDENTIAL

TI-COATED PEEK PEKK

Osseointegration of PEKK: Animal Studies

OsteoFab® Surface Properties:Bacteria Inhibition

Presented by Thomas Webster, Ph.D.


Bacteria Inhibition on PEKK: A Mechanistic Understanding

Thomas J. Webster, Ph.D.The Arthur W. Zafiropoulo Professor

SCOPUS Highly Cited Researcher (Top 1% Materials Science)Department of Chemical Engineering

Northeastern University, Boston, MA 02115 USAPast-President, U.S. Society For BiomaterialsEditor, International Journal of Nanomedicine

Associate Editor, Nanomedicine: NBMFellow, AANM, AIMBE, BMES, FSBE, IJN, NAI, and RSM

[email protected]

Nanostructured Surfaces Can Control Cell ResponsesWithout Drugs, Antibiotics, or Anti-inflammatories

Increased Bone Growth: 3D Printing Amputee: Increased Wound Healinga b

c d

e f

1 mm 500 µm

20 µm 10 µm

5 µm5 µm

Hive-3

Not Nano vs. Nano

Increased Bone

Growth

Specific Example:

Oxford Performance Materials

PEKK

Bacteria Results: Colony Forming UnitsCFU x 10^7/ml

Data = mean +/- SEM; N = 3; all values significantly different than each other except Ti versus PEEK after 1 day

PEKK inhibited bacteria

colonization


Data = mean +/- SEM; N = 3; all values significantly different than each other, except Ti and PEEK.


colonization


Data = mean +/- SEM; N = 3; all values significantly different than each other.


colonization

Bacteria Results: Percent LiveColor intensity (arbitrary units)

Data = mean +/- SEM; N = 3; all values significantly different than each other except Ti and PEEK.

1 5 7

PEKK resisted bacteria

colonization

Bacteria Results: Percent LiveColor intensity (arbitrary units)



colonization

Bacteria Results: Live/DeadColor intensity (arbitrary units)



colonization

Summary 1:

Results of this study showed:

• Decreased bacteria colonization on PEKK samples compared to PEEK and Ti.

• Decreased percentage of live cells on PEKK samples compared to PEEK and Ti.

• Impressively, MRSA showed the most drastic decrease on PEKK samples compared to PEEK and Ti.

But Why ????

Why ????

Pogodin et al. Biophysical model of bacterial cell interactions with nanopatterned cicada wing surfaces. Biophys. J. 2013, 104, 835-840.

Nanopillars on cicada wings are antibacterial, irrespective

of surface chemistry.

Biophysical model of bacterial cell interactions with nanopillars

Mechanism: As the bacteria try to attachonto the nanopillar structures, the cellmembrane stretches in the regionssuspended between the pillars. If thedegree of stretching is sufficient, this maylead to no attachment or cell rupture.

Pogodin at al. Biophysical model of bacterial cell interactions with nanopatterned cicada wing surfaces. Biophysical Journal, Volume 104,

pp. 835-840, 2013.

And we have a predictive equation for this:

This predicts the X, Y, and Z nanoscale features toinhibit bacteria, limit inflammation, and promote tissue growth

Changes in the type and bioactivity

of adsorbed proteins

Micro Nano

Surface Characterization: Surface Energy

Surface Energy/Surface Tension (mN/m)

Ti 62.5

PEEK 16.3

PEKK 35.7

Casein 48.0a

Mucin 42-46b

Lubricin 40c

a Colloid and Interface Chemistry for Nanotechnology, CRC Press, 2014. b B. Nagyová and J.M. Tiffany, “Components responsible for the surface tension of human tears,” Journal Current Eye Research 19(1): 4, 1999.c B. Nappone et al, “Adsorption, lubrication, and wear of lubricin on model surfaces: Polymer brush-like behavior of a glycoprotein,” Biophysical Journal, 92(5): 1693, 2007.

PEKK surface energy closer to proteins

that naturally resist bacteria colonization

https://www.tandfonline.com/author/Nagyov%C3%A1%2C+B

https://www.tandfonline.com/author/Tiffany%2C+JM

Promotion of Selection Protein Adsorption:

ELISA Intensity

Ti 0.1

PEEK 0.1

PEKK 0.6

Casein Adsorption (intensity)

ELISA Intensity

Ti 0.2

PEEK 0.1

PEKK 0.8

ELISA Intensity

Ti 0.1

PEEK 0.1

PEKK 0.3

Mucin Adsorption (intensity)

Lubricin Adsorption (intensity)

PEKK increased the adsorption of proteins

that naturally resist bacteria colonization

Correlation of Protein Adsorption to Minimized Bacteria Colonization

Staph epi and Casein: Colony Forming UnitsCFU x 10^7/ml

Data = mean +/- SEM; N = 3; all values significantly different than each other


Pseudo and Casein: Colony Forming UnitsCFU x 10^7/ml



MRSA and Casein: Colony Forming UnitsCFU x 10^7/ml


Same for all other

bacteria andproteins

Summary 2:

Results of this study showed:

• The surface energy of PEKK increased the adsorption of key antibacterial proteins: mucin, casein, and lubricin.

• The increased adsorption of these proteins decreased bacteria colonization.

• The “mechanism of action” for decreased bacteria colonization on PEKK is related to its optimal surface energy which enhanced the adsorption of endogenous antibacterial proteins.

Biomedical

21st CENTURYENABLING TECHNOLOGIES

Thank you and please stop by our booth in the Exhibitor Hall!

www.oxfordpm.com


Documents

Biomedical€¦ · Biomedical 21st CENTURY ENABLING TECHNOLOGIES 3D Printed PEKK Polymer: Enabling a Family of Medical Devices that Inhibit Bacterial Growth without the Use of Antibiotics