http://www.mech.kuleuven.be/en/bme/research/mechbio/

http://en.wikipedia.org/wiki/Graphene

Tissue Engineering CHE 418/518

Graphitic Carbon Materials for

Bone Tissue Engineering

Bone Tissue Engineering

There are approximately 500, 000 surgical procedures performed every year

in the U.S. which require bone substitutes.

1. Interconnected micro-pores (for vascular formation and waste transportation)

2. Optimal porosity with adequate surface area and mechanical strength

3. Biodegradable

4. Biocompatible

http://www.cs.cmu.edu/~tissue/

Tissue Engineering CHE 418/518

Carbon Nanotubes

Allotropes of carbon with a cylindrical nanostructure

http://what-when-how.com/nanoscience-and-nanotechnology/carbon-nanotubes-and-other-carbon-materials-part-1-nanotechnology/

Single walled carbon nanotubes

Multi-walled carbon nanotubes

http://nanopedia.case.edu/

Mechanical strength Electric properties

metallic nanotubes

current density 4 × 109 A/cm2

1000 times better than copper

Biocompability ???

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

(1) How do the carbon nanotubes affect the pore structure/porosity and mechanical

properties of scaffolds?

(2) What are the responses of cells cultured on scaffold made of different

nanomaterials with varying porosity?

Bone Cell Proliferation on CarbonNanotubes

Nano Lett., 2006, 6 (3), pp 562–567

CNTs sustain osteoblast growth and bone formation;

Surface charge/modification play an important role for

osteoblast proliferation.

What have been done?

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

Highly Ordered MWNT-Based Matrixes:  Topography at the

Nanoscale Conceived for Tissue Engineering

Langmuir, 2006, 22 (12), pp 5427–5434

This method aims to create architectures and topographies that mimic those

occurring naturally (native tissue structures).

(a) PLGA, (b) PLGA/MWCNTs, and (c) PLGA/c-

MWCNTs

Possessed higher tensile strengthPromoted the attachment, proliferation, and ALP secretion of rat MSCs

Colloids and Surfaces B: BiointerfacesVolume 83, Issue 2, 1 April 2011, Pages 367-375

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

Journal of Biomedical Materials Research Volume 59, Issue 3

Electrical stimulation (10 mA at 10 Hz) for 6 h/day for various periods of time, 46% increase in cell proliferation after 2 days, 307% increase in the concentration of extracellular calcium after 21 consecutive days,

Carbon Volume 49, Issue 10, August 2011, Pages 3284-3291

Multiwalled carbon nanotube-coating of 3D collagen scaffolds for bone tissue engineering

Rat primary osteoblasts (ROBs) were cultured,Significantly more bone formation was observed around the MWCNT-coated sponges

Tissue Engineering CHE 418/518

What next?

Carbon Nanotubes for Bone Tissue Engineering

3-D scaffolds comprised of CNTs with controlled

size/distribution/surface modification and their

evaluation for bone tissue engineering

Formation of 3-D scaffold

Control size/distribution/surface modification for CNTs

Incorporation in polymer

Evaluate the charge effect

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

Formation of 3-D scaffold

Conventional: Carbon nanotubes were separately synthesized and then dispersed,

Can we arrange carbon nanotubes in controlled 3-D fashion?

Adv. Mater. 44/2009

Nature Materials 10, 424–428 (2011)

Three-dimensional flexible and conductive

interconnected graphene networks

Graphene

Carbon nanotubes

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

ACS Nano, 2011, 5 (8), pp 6403–6409

http://www.azonano.com/article.aspx?ArticleID=1405

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

The diameter is only dependent on the size of nanoparticles,

The distribution is only dependent on the density of nanoparticles,

Selectively decorating graphene layer with catalytic nanoparticles

Formation of 3-D scaffold comprised of arranged carbon nanotubes

Covalent binding between graphene and NPs

Why important? Mechanical signal

Dimension and distribution of carbon nanotubes in 3-D fashion directly decide the topography of the scaffold, which has a great impact on proliferation and differentiation of cells.

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

Modification of 3-D scaffold comprised of arranged carbon nanotubes

1. Hydrophobic/Hydrophilic2. Neutral/Negative/Positive charge

Characterization

1. SEM and TEM

2. FTIR for surface functional group functionalization

3. Cell culturing

Confirmation of desired structure

Confirmation of desired surface groups

Effect of mechnical signal for growth of cells (Cell number, differentiation, adhesion)

acid

-COOH

-COOH

-COOH

-COOH

-COOH

Carbon Nanotubes for Bone Tissue Engineering

Incorporation in polymer

PLGA poly(lactic-co-glycolic acid

FDA-approved, easily processed, relatively inexpensive, biodegradable polymerDegradation of PLGA resulted in lactic acid and glycolic acid, can be removed from the body by metabolic pathways,

The application of PLGA has been limited by the weak mechanical strength.

Combined with 3-D scaffold comprised of CNTs and

graphene network

Surface modification + polymerization

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

Mechanical strength evaluation

Strength of composite should

be enhanced greatly.

Effect of carbon nanotubes for degradation

Degradation of PLGA can be controlled by alternating hydrophilic and

hydrophobic region, could presence of CNTs (hydrophobic/hydrophilic)

accelerate/decelerate the degradation of scaffold?

Effect of addition of 3-D scaffold for bone cell fomation

(Cell number, differentiation, adhesion)

Colloids and Surfaces B: BiointerfacesVolume 83, Issue 2, 1 April 2011, Pages 367-375

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

Electrical stimulation

supply

Only junction of CNTs could provide

electrical signal path, localized and non-

uniformUniform path, conclusive about

the effect of electrical signal

Tissue Engineering CHE 418/518

Carbon Nanotubes for Bone Tissue Engineering

Possible outcome

1. Formation of 3-D scaffold comprised of graphene and carbon nanotubes,

2. Evaluation of cell behavior/response with respect to this 3-D scaffold by

changing topography/surface functional groups,

3. Application of 3-D scaffold into polymer scaffold for enhancement of

mechanical strength,

4. Effect of 3-D scaffold for degradation of PLGA due to extra reaction sites,

5. Effect of electrical signal for bone cell growth,

6. Evaluation of long term effect of graphitic carbon materials for bone tissue

engineering.

Tissue Engineering CHE 418/518