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Dec 6, 2012 (4 years and 7 months ago)

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Developing Biofunctional Composite
Materials for Medical Applications

Yizhi Meng, Ph.D.

Assistant Professor



Materials Science and Engineering

Chemical and Molecular Engineering

Stony Brook University


November 3, 2011


Advanced Composites Manufacturing Conference

The
Morrelly

Homeland Security Center

Bethpage, New York

Materials
Science &
Engineering

Biomedical
Engineering

Chemical &
Molecular
Engineering

Meng Group @ SBU

Current focus areas:


“Green” nanobiocomposites


Drug/gene delivery


Cell
-
materials interactions


Basic Research


Technological Innovation


Translational Medicine


Education and Training

SBU
:


Strategic Partnership for Industrial Resurgence (SPIR)


Garcia Center for Polymers at Engineered Surfaces


Center for Thermal Spray Research


Center for Biotechnology


Center for Cancer Genetics


Centers for Molecular Medicine


Institute of Chemical Biology and Drug Discovery


Sensor CAT


BNL
:


National Synchrotron Light Source


Center for Functional Nanomaterials

Osteoporosis
-
related injuries


$18+ billion (2002)


450,000+ knee
replacements (2006)


180,000 hip replacements
(2006)

Bone is a nanocomposite material

Beniash, E. 2011.
WIRES

3:47
-
69.

Oyen, M. 2008.
MRS Bull.

33:49
-
55.

Water (10%)

Organic
matrix (20
-
30%)

Apatite mineral (60
-
70%)

organ

tissue

cell

material

Pros:


Less batch
-
to
-
batch
variation


Mechanically stable


Easily tunable chemistry and
viscosity


Many are FDA approved

Cons:


Not usually biodegradable


May induce inflammatory
responses in the long
-
term
(>12 wks)


Toxic precursors


Energy intensive processing

Synthetic

Polymers

Polyethylene

PLLA

PCL

Shastri, V.P., Martin, I. and Langer, R. 2000.
PNAS

97(5):1970
-
1975.

http://www.nbtc.cornell.edu/research/project_summaries/2009/BDA/bda19.htm

Pros:


Closely mimic native cellular
environment


Nontoxic processing and
degradation components


Cons:


Batch
-
to
-
batch variation


Limited mechanical
performance


Endotoxin level

Natural
Polymers

chitosan

cellulose

400 nm

starch

Eichhorn
, S.J., et al. 2010.
Journal of Materials Science
45:1
-
33.

Paradigm of the 3 B’s

Bio
-
derived

Biodegradable

Biofunctional

?


Porous architecture


High compressive strength
(apatite mineral)

o
130
-
180 MPa (cortical)

o
4
-
12 MPa (cancellous)


High tensile strength
(collagen matrix)

o
50
-
150 MPa (cortical)

o
1
-
5 MPa (cancellous)

Criteria

for Bone Tissue Engineering


Dynamic remodeling

process
(proteases, growth factors)


Electromechanically
responsive (piezoelectric)

Martin, Burr, Sharkey,
Skeletal Tissue Mechanics

(1998)


Metals


Ceramics


Glass

?

Zhang, C., and Meng, Y. 2011.
M.S. thesis.

Design Concept: Porosity

Necessary

for


Cell migration


Diffusion of nutrients and waste


Traditional methods


Solvent casting (high temperature)


Particulate leaching (limited
thickness)


More recent methods


Fiber bonding (organic solvents,
high temperature)


Phase separation (organic solvents)


Microwave drying (low porosity)

SC
-
CO
2

as
a “green”
porogen

Design Concept: Mechanical

Strength

Fiber Bonding

Woodfield TBF, et al. 2004.
Biomaterials

25:4149
-
4161.

Rapid Prototyping

Schumacher M, et al. 2010.
Journal of Materials Science
21:3119
-
3127.

Design Concept: Biofunctionality

Biodegradability


Minimizes the need for a
second surgery


Does not cause a local
increase in acidity (e.g.
synthetic aliphatic
polyesters)


Biocompatibility


Promotes cell attachment
and tissue integration


Osteoinductivity


Stimulates new bone
growth

Li, L., Lu, X., Weyant, C., and Meng, Y.
(submitted)

Electrochemical
Deposition

Layer
-
by
-
Layer (LBL)
Assembly

Alcantara, A.C.S., Darder, M., and Ruiz
-
Hitzky, E. 2010.
J. Mater. Chem.
20:9495
-
9504.

Kolambkar YM, et al. 2011.
Biomaterials

32:65
-
74.

PCL nanofibers

Polymeric Biohybrid Composites

Freiberg S. 2004.
International Journal of Pharmaceuticals

282:1
-
18.

Berkland C, et al. 2002.
Journal of Controlled Release

82:137
-
147.

Gupta P, et al. 2002.
Drug Discovery Today

7:569
-
579.

copolymers

blends

Polymeric Biohybrid Composites (cont’d)

In Vivo Considerations of Drug Delivery

Plasma concentration

Time

Conventional tablet

Sustained release

Zero
-
order controlled release

http://www.sigmaaldrich.com/materials
-
science/biomaterials/tutorial.html

Vukomanovic M, et al. 2011.
Colloids and Surfaces B: Biointerfaces

82:404
-
413.