Seminar at Shanghai Jiao Tong University,
Shanghai, 10-Jul-2012
Advances in Nanodiamond for
(Bio)Composite Applications
Vadym Mochalin
Drexel University
AJ Drexel Nanotechnology Institute, Materials Science
and Engineering Department
E-mail: vadym@coe.drexel.edu
Web: www.pages.drexel.edu/~vnm25/
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Drexel University, College of Engineering,
Department of Materials Science
Drexel University:
Sacramento,
CA
Bossone building
(home to College of
Engineering labs)
Philadelphia,
PA
Founded in 1891 by financier and philanthropist Anthony J. Drexel
Location: five campuses: 3 in Philadelphia, 1 in New Jersey (Mt. Laurel), 1 in
California (Sacramento)
Student Enrollment: 13,484 undergraduates 9,009 graduate and
professional students
Student Geographic Distribution: Students come from 50 U.S. states and 130
foreign countries. Nearly 8% are international students
Our lab
Materials Science and Engineering Department :
Students: Undergraduate: 93, Graduate: 89
Faculty: 13, Affiliated Faculty: 12, Emeritus Faculty: 7, Staff: 6
Drexel University’s doctoral program in Materials Science and Engineering is rated
among the top ten MSE programs nationwide (2007)
More information at: http://www.materials.drexel.edu/News/AnnualReport/
Nanomaterials Group, Prof. Yury Gogotsi
Nanoporous Carbide Derived Carbons – gas (H2, CH4) and
electrical energy storage, catalysis, water desalination
Nature, v. 367, 628 (1994) & v. 411, 283 (2001), Science, v. 313, 1760 (2006)
Nanotubes – sensors, composites, cellular probes, nanofluidics
Science, v. 290, 317 (2000)
TiO2 coatings for self-cleaning and bactericidal surfaces
Nanodiamond – nanocomposites, drug delivery
Nature Nanotechnology, v. 7 (1), 11 (2012)
Material Synthesis, Testing and Characterization
Nature, v. 401, 663 (1999), Nature Materials, v. 7, 845 (2008)
Structure of ND Particle
a
b
c
d
V. N. Mochalin, O. Shenderova, D. Ho, Y. Gogotsi, Nature Nanotechnol. 7, 11-23 (2012)
Detonation Synthesis of Nanodiamond
a
b
c
40
1.2 nm
CH3
NO 2
NO 2
O 2N
N
N
NO 2
N
NO 2
bulk
I
A
30
Pressure, GPa
O 2N
2 nm
II
Diamond
20
Liquid
Explosive
charge
CNOH →
N2+H2O+CO+CO2+C
T, K
Low
High
III
V
IV
VI
10
Graphite
VII
50-500nm
5nm
0
2000
3000
4000
5000
Temperature, K
V. N. Mochalin, O. Shenderova, D. Ho, Y. Gogotsi, Nature Nanotechnol. 7, 11-23 (2012)
Nanodiamond: Combining the Best of Both Worlds
N subst
NV center
N conglomerate
5 nm
Nanodiamond (ND) particle
Biomedical applications:
Particles are less than 30 nm (can penetrate
cell membranes and exit through kidney)
Can be assembled into 100-1000 nm
agglomerates
Stable core
Rich tailorable surface chemistry (versatile drug
delivery platforms)
Can be made fluorescent (biomedical imaging)
Least toxic of all carbon particles (less toxic
than ubiquitous carbon black)
Composite applications:
Small 5nm particle size
Large and accessible surface area
Excellent mechanical properties:
Young’s modulus ~1220 Gpa
Superior hardness
High thermal conductivity
Low cost and existing industrial production
Nanodiamond Applications: Key to Success
, Purity, and Characterization
Normalized intensity (a.u.)
a
I - Larger and
II - Smaller
scattering domains
ND
C=C
ND
sp3
O-H
b
C=O
I
1200
1300
1400
1500 1600 1700 1800
1640
O-H + C=C
1760
C=O
1410
D-Band
1200
Ozone (J. Phys. Chem. C 115, 9827–9837 (2011))
1590
G-Band
1328
Diamond
1400
1600
Liquid
Diamond:
Synthesis, Properties, and Applications, William Andrew,
2006)
Gas purification:
Air (J. Am. Chem. Soc. 128, 11635–11642 (2006))
II
1100
Purification strategies:
oxidation (Ultrananocrystalline
Hydrogen (ACS Nano 4, 4824–4830 (2010))
Oxidized ND
ND
Functionalization strategies:
Detonation soot
Gas chemistry (Diamond Relat. Mater. 15, 296–299
1800
2000
-1
Raman shift (cm )
V. N. Mochalin, O. Shenderova, D. Ho, Y. Gogotsi, Nature Nanotechnol. 7, 11-23 (2012)
sp2
(2006))
Wet chemistry (Nature
Nanotechnol. 7, 11-23 (2012);
Adv. Funct. Mater. 22, 890-906 (2012))
Nanodiamond Purification by Air
Air Oxidation
T = 425°C, 5h
As-received ND soot
High purity ND
S.Osswald, G.Yushin, V.Mochalin, S.Kucheyev, Y.Gogotsi, J.Am.Chem.Soc.(2006)128:11635-11642
HN
ND
H2N
NH3, T
O
LiAlH4
ND
ND
OH
OH
Hydrophilic
Further reactions
N
Cl
Other reactions
Further purification/reactions
ND Chemistry (Simplified)
O
O
ND
Cl
ND
OH
ND
Cl
H
H
H2, T
O
O
ND
ND
ND
H
NH-R
NH-R-NH 2
Inert, hydrophobic
Attachment of proteins
and polymers
Fluorescent, hydrophobic
Imaging, composites
V. N. Mochalin, O. Shenderova, D. Ho, Y. Gogotsi, Nature Nanotechnol. 7, 11-23 (2012)
A. Krueger, D. Lang, Adv. Funct. Mater. 22, 890-906 (2012)
Biodegradable Polymers in Bone Surgery
Bone plates
and screws
Currently used bone fixation
devices are made of metal (Ti
alloys) and have to be surgically
removed (second surgery) after
bone healed
Metals have limited ability to
provide support for osteoblast
growth
Screws
Screw
©MMG1999
Bicortical
screws
H
H
O
O
O
O
H
H
H
O
H
O
H
n
O
H
H
O
O
Plate
H
H
O
H
H
Poly (L-lactic acid)
Biodegradable polymer produced from renewable
source with a very broad range of applications
O
H
Gradient porous structure: from coarse
to fine pores on the screw wall
Hydrogel fillings:
Embedded with
healing drug, growth
factor and cells
Possible design of bioactive biodegradable surgical screw with gradient porosity
Biodegradable polymer surgical
fixation devices do not require
additional extraction surgery
They can be make porous serving
as scaffolds for bone re-growth
Drugs and growth factors can be
loaded into pores
One problem – mechanical strength
is poor
Nanodiamond Comes to the Rescue
ND-PLLA Composites: Manufacturing
ND core
-(CH2)14-CH2-CH3
Cross polarization
Direct polarization
missing -NH-CH2-CH2-
-CH2-CH3
-CH3
1 nm
100
ND
80
60
40
20
Chemical Shift (ppm)
ODA
ND-ODA
0
ND
ND-ODA/PLLA
0.206 nm
Bone fixation with fluorescent
biodegradable ND-ODA/PLLA devices
Biodegradable fluorescent
ND-ODA/PLLA screw
5 nm
Q. Zhang, V. N. Mochalin, I. Neitzel, I. Y. Knoke, J. Han, C. A. Klug, J. G. Zhou, P. I. Lelkes, Y. Gogotsi, Biomaterials 32, 87-94 (2011)
ND-PLLA Composites: Dispersion
1% wt NDODA/PLLA
Volumes, %
30
(2)
10% wt NDODA/PLLA
(1)
20
10
0
0
50
1% wt. ND
150
3% wt. ND
PLLA matrix
ND-ODA
100 nm
100
Size, nm
200
10% wt. ND
ND-ODA
ND-ODA
PLLA matrix
100 nm
100 nm
Q. Zhang, V. N. Mochalin, I. Neitzel, I. Y. Knoke, J. Han, C. A. Klug, J. G. Zhou, P. I. Lelkes, Y. Gogotsi, Biomaterials 32, 87-94 (2011)
PLLA
matrix
ND-PLLA Composites: Nanoindentation
Load (mN)
30
Creep: 164nm
Creep:
20
250nm
10
0
0
400 800 1200 1600
Displacement (nm)
Sample Composition
pure PLLA
1 % wt ND-ODA/PLLA
3 % wt ND-ODA/PLLA
5 % wt ND-ODA/PLLA
7 % wt ND-ODA/PLLA
10 % wt ND-ODA/PLLA
1 % wt UD90/PLLA
3 % wt UD90/PLLA
Young’s Modulus
(GPa)
2.6±0.1*
5.3±0.2
5.5±0.3
5.9±0.3
6.8±0.5
7.9±0.1
2.8±0.2
2.7±0.1
Stress (GPa)
0% ND-ODA/PLLA
1% ND-ODA/PLLA
10% ND-ODA/PLLA
0.5
0% ND-ODA/PLLA
1% ND-ODA/PLLA
0.4
10% ND-ODA/PLLA
0.3
0.2
0.1
0.0
0.00 0.02 0.04 0.06 0.08 0.10
Strain (%)
Increase
(%)
0
107
113
129
165
206
9
5
Hardness
(GPa)
0.05±0.01
0.21±0.01
0.25±0.01
0.26±0.01
0.31±0.06
0.46±0.05
0.12±0.01
0.11±0.01
Increase
(%)
0
320
400
420
520
820
140
120
Q. Zhang, V. N. Mochalin, I. Neitzel, I. Y. Knoke, J. Han, C. A. Klug, J. G. Zhou, P. I. Lelkes, Y. Gogotsi, Biomaterials 32, 87-94 (2011)
ND-PLLA Composites: Bulk Mechanical Properties
0% wt. ND
120
1% wt. ND
90
Crazing
PLLA
1% ND-ODA/PLLA
5% ND-ODA/PLLA
10% ND-ODA/PLLA
60
30
5% wt. ND
0
0
1
2
4
5
Strain (%)
60
Stress (MPa)
3
PLLA
1% ND-ODA/PLLA
5% ND-ODA/PLLA
10% ND-ODA/PLLA
0
Fibers and larger
deformation
10% wt. ND
30
0
2
4
6
8
10
12
14
16
18
10% wt. ND
Large
deformation
10% wt. ND
Fibers bridging pores
20
Strain (%)
Slight increase in apparent modulus in compression for 1-10% wt. ND-ODA compared to neat PLLA
Steady increase in strain at failure and fracture energy upon addition of ND
300% increase in strain at failure and fracture energy for 10% wt. ND-ODA compared to neat PLLA
Q. Zhang, V. N. Mochalin, I. Neitzel, K. Hazeli, J. Niu, A. Kontsos, J. G. Zhou, P. I. Lelkes, Y. Gogotsi, Biomaterials (2011) – in press
Tension direction
Stress (MPa)
Sharp deformation
ND-PLLA Composites: Cell Growth and Biomineralization
ND-ODA/PLLA
scaffold
scaffold
cell layer
cell layer
Cytoskeleton
cell layer
scaffold
cell layer
Cell nuclei
100 μm
3 days
100 μm
Time of incubation in simulated body fluid
5 μm
6 weeks
Scale bars are 10 μm
Upper row (a-e) – neat PLLA; bottom raw (f-j) – 10% wt. ND-ODA in PLLA
Q. Zhang, V. N. Mochalin, I. Neitzel, K. Hazeli, J. Niu, A. Kontsos, J. G. Zhou, P. I. Lelkes, Y. Gogotsi, Biomaterials (2011) – in press
ND-PLLA Composites: ND-ODA Enhances Biomineralization
0.4
2
1.5
1
0.5
0
0
7
SBF
14
21
28
35
Incubation time (days)
SBF
Na+
HCO3-
42
SO42-
4
5
SBF
Form a layer
of Ca2+
Mg2+
33
2+
Ca2+ Ca
7
78
10 11 121413 14
9
SBF
Form a layer
of HPO42-
HPO42-
Ca2+ layer
Ca2+
6
Incubation time (days)
ClHPO42-
Ca2+
2
2.5
0
K+
1
3
5% ND-ODA/PLLA
0.8
1% ND-ODA/PLLA
1.2
PLLA
1.6
3.5
10% ND-ODA/PLLA
4
PLLA
1% wt ND-ODA/PLLA
5% wt ND-ODA/PLLA
10% wt ND-ODA/PLLA
Particle diameter (µm)
Weight Increase (μg)
2
HPO42- HPO 24
2+
Ca2+ Ca
+
+
+
+
HPO42- HPO4
+
+
+
Ca2+
Ca2+
Ca2+
HPO42HPO42-
HPO42HPO42-
Ca2+
2-
+
+
Bonelike apatite layer
-COOH
PLLA
NDODA
ODA
(1)
PLLA
PLLA
(2)
PLLA
(3)
(4)
Un-reacted COOH groups on ND-ODA surface may assist the bonelike apatite formation on ND-ODA – PLLA
Further studies required to better understand the mechanism of the enhancing action of ND
Q. Zhang, V. N. Mochalin, I. Neitzel, K. Hazeli, J. Niu, A. Kontsos, J. G. Zhou, P. I. Lelkes, Y. Gogotsi, Biomaterials (2011) – in press
Covalent Incorporation of ND into Polymers
OH
OH
N
OH
HO
ND
OH
OH
NH2
O
+
OH
HO
N
N
OH
O
ND
OH
HO
HO
OH
OH
HO
N
HO
t°
ND
ND
OH
OH OH
OH
HO
HO
H2 N
OH
N
OH
N
OH
OH
OH
N
OH
ND
OH
HO
OH
N
OH
Schematic of covalent incorporation of aminated ND
into a structure of epoxy polymer
Simplified molecular model of the resulting covalently
bonded composite
Route to aminated ND (ND-NH2):
O
O
SOCl2
H3C
ND
700C, 24h
OH
O
NH2(CH 2)2NH2
H3C
ND
600C, 24h
Cl
H3C
ND
NH(CH 2)2NH2
V. N. Mochalin, I. Neitzel, B. J. M. Etzold, A. Peterson, G. Palmese, Y. Gogotsi, ACS Nano 5, 7494-7502 (2011)
Nanodiamond for Drug Delivery
a
b
3. Drug efflux
Nanodiamond-drug
complex
c
ND-Dox
ND-Dox
Dox
Dox
ABC
transporter
2. Passive diffusion
Free drug molecules
1. Particle uptake
PBS
PBS
T. J. Merkel, J. M. DeSimone, Sci. Transl. Med. 3, 73ps8 (2011)
E. K. Chow, X.-Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, D. Ho, Sci. Transl. Med. 3, 73ra21 (2011)
V. N. Mochalin, O. Shenderova, D. Ho, Y. Gogotsi, Nature Nanotechnol. 7, 11-23 (2012)
ND for Drug Delivery: Adsorption
pH<7 Release
pH>7 Adsorption
Dox
ND
H2O
A. Adnan, R. Lam, H. Chen, J. Lee, D. J. Schaffer, A. S. Barnard, G. C. Schatz, D. Ho, W. K. Liu, Mol. Pharmaceutics, 2011, 8 (2), pp 368–374
Drug delivery with nanodiamond via adsorption/desorption
mechanisms:
Do we know optimal surface chemistry for doxorubicin?
Do we know it for millions of other drugs?
Do we know how pH, electrolyte concentration, presence of
other biomolecules, temperature, and other factors will change
the adsorption/desorption behavior?
Do we know kinetics of adsorption/desorption depending on ND
particle size, surface chemistry, and the effects of the
environment?
Do we know mechanisms of adsorption?
L. C. L. Huang, H.-C. Chang, Langmuir 20, 5879–5884 (2004)
ND for Attoliter Separation
Carbon Nanotube Packed with Nanoparticles
www.nature.com/scientificreports
Separation and liquid chromatography using a single carbon nanotube
Riju Singhal, Vadym Mochalin, Maria Lukatskaya, Gary Friedman & Yury Gogotsi
Conclusions
Well purified, characterized, and modified nanodiamond is an excellent material for
many biomedical applications
Nanodiamond terminated with long hydrocarbon chains (ND-ODA) significantly
increases local (nanoindentation) and bulk mechanical properties when incorporated
into biodegradable polymers
In addition to increased mechanical properties, incorporation of ND-ODA into poly (LLactic acid) enhances biomineralization, an important factor in bone tissue
engineering
Modified ND can be used to adjust adsorption/desorption behavior of drugs, in
particular, antibiotics in nanodiamond based drug delivery systems
Mechanisms of adsorption and desorption of different drugs by nanodiamonds with
different surface chemistry are crucial in development of drug delivery systems and
need to be further studied
Acknowledgments
Collaborators:
Students:
Prof. Peter Lelkes (Drexel University)
Prof. Jack Zhou (Drexel University)
Prof. Noreen Hickok (Thomas Jefferson
University)
Amanda Pentecost
Matt Nelson
Ioannis Neitzel
Riju Singhal
Maria Lukatskaya
National Science Foundation (CMMI-0927963)
FIRST (Fluid Interface Reactions, Structures and Transport), an Energy Frontier Research
Center funded by the US Department of Energy Office of Science, Office of Basic Energy
Sciences
NanoWound Devices, Inc.
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