Group Meeting

NEIL BERNARD
DEPARTMENT OF POLYMER SCIENCE
THE UNIVERSITY OF AKRON

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Becker Laboratory for Functional Biomaterials
 Introduction
Total joint replacements have skyrocketed in the United States
Total hip and knee surgeries will reach 4 million procedures annually by
2030
Total hip replacement and total knee replacement both use titanium as
the implant material
High success rate

Steven, K., et al. JBJS 2007, 89, 780-785. 2

Becker Laboratory for Functional Biomaterials
 Complications
Patients with predisposed diseases like diabetes have shown to
have increased complications
Infections
Aseptic loosening
Complications are due to a lack of bone growth around the
implant
Failure of osseointegration
Results in revisional surgeries, which can have poor success
rates and severe complications

So what is the solution?

Create a bioactive peptide coating that is able to communicate with the

body and promote a desired response

Siqueira, J.T., et al. Implant Dent 2003, 12, 242.

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Becker Laboratory for Functional Biomaterials
 OGP-PEG-(Cat)4

Osteogenic Growth Peptide (OGP)

provides the bioactive cues to recruit
necessary cells and signals to start
bone growth

Catechol groups
provide strong
binding to titanium

O O O O
Tang, W.; Policastro, G.; Hua, G.; Guo, K.; Zhou, Ti Ti Ti Ti
J.; Wesdemiotis, C.; Doll, G.; Becker, M. J. Am. O O O
Chem. Soc. 2014, 136, 16357-16367. 4
Becker Laboratory for Functional Biomaterials
 Research Goal

1. Extend this modular system to different peptides: Bone morphogenetic Proteins 2,

7, 9 (BMP-2, BMP-7, BMP-9)
2. Study the performance of the 4 molecules (OGP, BMP-2, BMP-7, and BMP-9) in a
rat model

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Becker Laboratory for Functional Biomaterials
 Peptide Sequences

Synthesized via microwave-assisted solid-phase peptide synthesis

Based on Fmoc protecting group strategy
Easy way to synthesize chemically and still retain bioactivity

Peptide Sequence
OGP (10-14) YGFGG
BMP-2 (73-92) KIPKASSVPTELSAISTLYL
BMP-7 (89-117) TVPKPSSAPTQLNAISTLYF
BMP-9 (68-87) KVGKASSVPTKLSPISILYK
bFGF (105-111) YKRSRYT

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Becker Laboratory for Functional Biomaterials
 Peptide synthesis
YGFGG

Wang-Gly-Fmoc

Wang-Gly-NH2

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Becker Laboratory for Functional Biomaterials
 Peptide synthesis
YGFGG

HTBU
Gly-Fmoc

Wang-Gly
Wang-Gly-Gly-Fmoc

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Becker Laboratory for Functional Biomaterials
 Peptide Synthesis
YGFGG

Wang-Gly-Gly-Fmoc

Phe-Fmoc

Wang-Gly-Gly-Phe-Fmoc

Wang-Gly-Gly-Phe-Gly-Tyr(boc)-NH2
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 PEG addition

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 Lysine addition

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 Lysine addition x2

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Becker Laboratory for Functional Biomaterials
 Catechol addition

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 Deprotection

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Becker Laboratory for Functional Biomaterials
 OGP-PEG-(Cat)4

Molecular Weight: 1876.06

Exact Mass: 1876.53

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Becker Laboratory for Functional Biomaterials
 OGP-PEG-(Cat)4
Intens. [a.u.]

x10 4 1898.526
1.2

1.0

0.8

0.6

0.4

2004.599
0.2

1079.843

2110.663

0.0
1000 1500 2000 2500 3000 3500
m/z

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Becker Laboratory for Functional Biomaterials
 OGP-PEG-(Cat)4

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Becker Laboratory for Functional Biomaterials
 The University of Akron Department of Polymer Science
Becker Laboratory for Functional Biomaterials
Dr. James Wilson

Jiayi Yu
Vrushali Bhagat
Shan Li
Yuanyuan Luo
Zach Zander
Cecilia Motta
Elena Silantyeva
Rodger Dilla
Alex Kleinfehn
Derek Luong
Garrett Bass
Jason Nettleton
Nathan Dreger
Shannon Petersen
Alexandra Abel
Collaborators Erik Crenshaw
ONLINE: Yen-Hao Hsu
Ali Dhinojwala, Bryan Vogt, Andrey Dobrynin, Rebecca Willits University of Akron
Andrew Dove, Rachel OReilly The University of Warwick
Becker Research Lab Yongjun Shin
Brad Weiner, Ennio Tasciotti Houston Methodist Research Institute TWITTER: Karissa Hagen
@MLBeckerGroup Keke Chen
Robert Latour Clemson University
Yusheng Chen
David Dean, Michael Miller Ohio State University Plastic Surgery Peiru Chen
Christopher Breuer, Tai Yi, Toshi Shinoka Nationwide Childrens Hospital & Ohio State University Shantanu Nikam
Natasha Brigham
FUNDING Emily OBrien
Kourtney Nannarone
NIH NIBIB & NIGMS (P41-0063563 & R15-GM113155) W. Gerald Austen Endowment Laura Savrinau
National Science Foundation (BME & CBET & BMAT & GFRP) Knight Foundation Neil Bernard
Ohio Third Frontier Innovation Platform Cook Medical, Cook Biotech
US Department of Defense US Army MRMC W81XWH-15-1-0718 Merck, 21MedTech 18
Becker Laboratory for Functional Biomaterials