Silicon Nanowires for Biomedical Applications

Ke Jiang, Ph.D

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Silicon Nanowires for Bone Tissue Engineering?

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Biological Roles of Silicon

Improve bone calcification in rat and chick. Edith M. Carlisle in the 1970s.

Initiate bone calcification in animals and stimulates formation of collagen.

“Significant positive association” between the density of bone and silicon

uptake in men and in premenopausal women.

An essential component in bioactive glasses as bone substitutes.

Potential Biological Applications of Silicon Nanowires

Biosensor

Drug delivery

Bio-scaffold

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Synthesis of SiNWs

VLS Growth Mechanism

1. Annealing of catalysts; 2. Introduction of SiH4; 3. Precipitation of SiNWs

from Si/Au liquid alloy.

Cathodic Bias-Induced Calcification of SiNWs

SBF = Simulated Body Fluid (pH ≈ 7.3) Ion Na+ K+ Mg2+ Ca2+ Cl- HCO3

- HPO42- SO4

2-

SBF (mM) 142.0 5.0 1.5 2.5 148.8 4.2 1.0 0.5

Blood Plasma (mM)

142.0 5.0 1.5 2.5 103.0 27.0 1.0 0.5

K. Jiang, D. Fan, Y. Belabassi, G. Akkaraju, J-L. Montchamp, J. L. Coffer, ACS Appl. Mater. Interface. 2009, 1, 266 4

Calcium Phosphate Coated SiNWs (CaP/SiNWs)

Graphite

Si (111) Si (220)

Si (311)

Au Graphite

CaP/SiNWs (synthesized by VLS method) CaP/SiNWs (synthesized by OAG method)

CaP

K. Jiang, D. Fan, Y. Belabassi, G. Akkaraju, J-L. Montchamp, J. L. Coffer, ACS Appl. Mater. Interface. 2009, 1, 266 5

Si

P

Ca

Si P

Ca

Before coating

After coating

Effect of Experimental Conditions on Calcification of SiNWs

Effects of Bias Conditions on Ca/Si Ratio Effects of Bias Conditions on Ca/P Ratio

SEM images of calcification of SiNWs as a function of immersion time in SBF (The sample was biased at a current density of 10 mA/cm2 for 90 min)

1 week 2 weeks 3 weeks 4 weeks

K. Jiang, D. Fan, Y. Belabassi, G. Akkaraju, J-L. Montchamp, J. L. Coffer, ACS Appl. Mater. Interface. 2009, 1, 266 6

Surface Modification of CaP/SiNW with Alendronate

Fluorescent Microscopy of FITC Labled Alendronate-CaP/SiNWs

Fluorescent Spectrum of FITC Labled Alendronate-CaP/SiNWs

K. Jiang, D. Fan, Y. Belabassi, G. Akkaraju, J-L. Montchamp, J. L. Coffer, ACS Appl. Mater. Interface. 2009, 1, 266 7

Alendronate Internalized by mature osteoclasts Inhibit resorptive function of osteoclasts Induce apoptosis of osteoclasts

Mouse Stromal Cell (MSC) Proliferation

K. Jiang, D. Fan, Y. Belabassi, G. Akkaraju, J-L. Montchamp, J. L. Coffer, ACS Appl. Mater. Interface. 2009, 1, 266

MSC proliferation on SiNWs, CaP/SiNWs, glucose bisphosphonate-CaP/SiNWs,

alendronate-CaP/SiNWs

Mouse Stromal Cells (MSCs) derived from bone marrow;

capable of differentiation into osteoblasts, chondrocytes, and adipocytes;

treat disorders such as osteoporosis.

Optical Image of MSC

10 µm

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Silicon Nanowire/Polycaprolactone (PCL) Nanocomposites as Biocompatible Scaffolds for Bone Tissue Engineering

SiNWs usually grow on rigid substrates; Flexible materials is desired;

SiNWs incorporated in a polymer matrix;

Polycaprolactone: slow degradation rate.

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Fabrication of SiNW/PCL Composites

Fabrication of SiNW/PCL Composites

K. Jiang, G. Akkaraju, J. L. Coffer, J. Mater. Res. In Press. 11

Printing Method Embedding Method

1 cm

Acellular Calcification of SiNW/PCL Composites

2 4 6 8

Energy (keV)

1.0K

Cnts

P

Ca

2.0K

Si

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2 4 6 8 Energy (keV)

20

40

Cnts

P

Ca

Embedding Method Printing Method

K. Jiang, G. Akkaraju, J. L. Coffer, J. Mater. Res. In Press.

SiNWs SiNW/PCL-2 SiNW/PCL-4 SiNW/PCL-6

1 week

2 weeks

3 weeks

MSC Attachment on SiNW/PCL Composites Fabricated by the Embedding Method

13 K. Jiang, G. Akkaraju, J. L. Coffer, J. Mater. Res. In Press.

MSC Attachment on SiNW/PCL-film Composites Fabricated by the Printing Method

SiNWs SiNW/PCL PCL Film

3 days

5 days

7 days

14 K. Jiang, G. Akkaraju, J. L. Coffer, J. Mater. Res. In Press.

MSCs Viability on SiNW/PCL Composites: MTT Assay

15 K. Jiang, G. Akkaraju, J. L. Coffer, J. Mater. Res. In Press.

ALP assay: MSC Differentiation on SiNW/PCL Composites

16 K. Jiang, G. Akkaraju, J. L. Coffer, J. Mater. Res. In Press.

1935 H. J. Taylor; 1936 G. L. Locher. Both α–particles and lithium ions have pathlength of several micrometers;

Boron-containing agents:

5B + 0n → [ 5B] → 2He2+ + 3Li3+ + γ0.48 MeV + 2.31 MeV 10 1 11 4 7

17 Dendrimer Liposome Dextran

Nanomaterials as Delivery Vehicles:

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SiNWs as Delivery Vehicles for Boron Neutron Capture Therapy (BNCT)

BSH

SiNWs as Delivery Vehicle for BNCT

0

20

40

60

80

100

120

0 200 400 600 800 1000 1200

After CoatingBefore Coating

Cou

nts

DiametersK. Jiang, J. L. Coffer, J. G. Gillen, T. M. Brewer, Chem. Mater., 2010, 22, 279.

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Dissolution of BSH from SiNWs as a Function of Time 0 min 5 min 10 min 15 min

20 min 25 min 30 min 40 min

50 min 60 min 80 min 100 min

120 min 3 h 6 h 10 h

19 K. Jiang, J. L. Coffer, J. G. Gillen, T. M. Brewer, Chem. Mater., 2010, 22, 279.

Dissolution of BSH from SiNWs as a Function of Time

Time (min)

Mol

ar R

atio

20 K. Jiang, J. L. Coffer, J. G. Gillen, T. M. Brewer, Chem. Mater., 2010, 22, 279.

Remarks

Catalyst-assisted chemical vapor deposition methods were employed to synthesize SiNWs, which were coated with calcium phosphate by an electrochemically induced method. The alendronate modified CaP/SiNWs exhibit a cytotoxic behavior, while deliberate subtle modification of the exposed primary amine with glucose sensitively improves the cytocompatibility of the nanowire vector.

SiNW/PCL composites with a variety of surface topography were fabricated and their cytocompatibility were tested in vitro. These composite materials show supportive behavior of directing mouse stromal cells attachment, proliferation, and differentiation functions. SiNWs can be used as potential delivery vehicles for boron-containing agents, therefore exhibited some properties favorable for possible use in Boron Neutron Capture Therapy.

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