Challenges and Opportunities for Applied
Nanotechnology to the Regeneration of the
Central Nervous System
Gabriel A. Silva, M.Sc., Ph.D.
Departments of Bioengineering and Ophthalmology,
Whitaker Institute for Biomedical Engineering and Neurosciences Program
University of California, San Diego
A Working Definition of Nanomedicine
Understanding, preventing, and treating diseases using tools,
materials, and approaches that take advantage of and operate
at the nanoscale.
(NIH Nanomedicine Roadmap Initiative meeting, May 4, 2004)
Model of Applied Nanotechnology to
Medicine and Physiology
Nanoscience and
Nanotechnology
Biology, Physiology,
and Medicine
Our research group focuses on experimental and theoretical
neural bioengineering aimed at increasing our fundamental
understanding of neuroscience and developing new
approaches for the clinical regeneration of the neural retina and
central nervous system (CNS).
We approach this, in part, through the development and
application of targeted nanotechnologies.
The Central Nervous System (CNS)
National Library of Medicine- www.nlm.nih.gov
The Central Nervous System (CNS)
Gray’
s Anatomy Online- http://www.bartleby.com
The Central Nervous System (CNS)
Gray’
s Anatomy Online- http://www.bartleby.com
The Central Nervous System (CNS)
Gray’
s Anatomy Online- http://www.bartleby.com
The Central Nervous System (CNS)
Nature Encyclopedia- http://www.els.net
The Cellular and Sub-Cellular Scales
Challenges faced by CNS Nanotechnologies
1. Integration with a highly specialized extracellular environment
2. Targeting to specific molecular elements (e.g. receptors, other
proteins), in particular intracellular targets
3. A very heterogeneous cellular environment
3. Highly restricted anatomical access
4. The complexity of the CNS’
s functional “
wiring”
5. Multiple specific targeted effects and/or responses
6. Optimization of desired integrated responses and minimization
of local and systemic “
side effects”
The Successful Development
Of CNS Nanotechnologies
Advancements in
basic and clinical
neuroscience
The integration
of the two
Advancements in
The fundamental chemistry,
physics, and materials
science of nanotechnology
Neural Specific Bioactive Peptide
Amphiphile Networks
O OH
NH2
H O
H O
H O
H O
H O
H O
H O
N
N
N
N
N
N
N
N
N
N
N
N
N
OH
O
H O
H O
H O
H O
H O
H O
C16H31O-NH-AAAAGGGEIKVAV-COOH
Hydrophobic Tail
Spacer Region
Functional Peptide Region
Stupp Research Group, Northwestern University- Jeffery Hartgerink and Elia Beniash
Neural Specific Bioactive Peptide
Amphiphile Networks
Stupp Research Group, Northwestern University- SEM by Dan Harrington
Neural Specific Bioactive Peptide
Amphiphile Networks
Stupp Research Group, Northwestern University- Gabriel Silva
Neural Specific Bioactive Peptide
Amphiphile Networks
Stupp Research Group, Northwestern University- Gabriel Silva
Neural Specific Bioactive Peptide
Amphiphile Networks
N
*
NF
2 m
Stupp Research Group, Northwestern University- Gabriel Silva
Neural Specific Bioactive Peptide Amphiphile
Networks: Cell Viability/Cytotoxicity
100
IKVAV-PA gel
PDL
1 DIV 7 DIV 22 DIV
1 DIV 7 DIV 22 DIV
Live cells (%)
80
60
40
20
100 um
0
Days in vitro
Stupp Research Group, Northwestern University- Gabriel Silva
70
**
60
50
40
*
30
20
10
0
1 DIV 7 DIV
IKVAV-PA gel
1 DIV 7 DIV
Laminin
1 DIV 7 DIV
PDL
GFAP+ cells/ total number of cells (%)
-tubulin+ cells/ total number of cells (%)
Neural Specific Bioactive Peptide
Amphiphile Networks
25
20
15
10
5
0
*
1 DIV 7 DIV 1 DIV 7 DIV 1 DIV 7 DIV
PDL
IKVAV-PA gel
Laminin
Stupp Research Group, Northwestern University- Gabriel Silva
Nanoengineering Mesenchymal Stem Cells
Differentiation into Photoreceptor Neurons
Silva Research Group, UCSD- Diana Yu and Mai Ho
Nanoengineering Mesenchymal Stem Cells
Differentiation into Photoreceptor Neurons
Silva Research Group, UCSD- Diana Yu and Mai Ho
Functionalized Quantum Dot
Targeting of Reactive Gliosis
Silva Research Group, UCSD- Smita Pathak
Functionalized Quantum Dot
Targeting of Reactive Gliosis
Silva Research Group, UCSD- Smita Pathak and Julie Schallhorn
Functionalized Quantum Dot
Targeting of Reactive Gliosis
Culture model of reactive gliosis
Untreated retinal glial cells
Ouabain treated retinal glial cells
Secondary treated retinal glial cells
Functionalized Quantum Dot
Targeting of Reactive Gliosis
Silva Research Group, UCSD- Julie Schallhorn
Functionalized Quantum Dot
Targeting of Reactive Gliosis
Silva Research Group, UCSD- Julie Schallhorn and Smita Pathak
URL: www.silva.ucsd.edu
Email: gsilva@ucsd.edu
Acknowledgments and Collaborators
Silva Lab, University of California, San Diego
Marie Davidson
Smita Pathak
Julie Schallhorn
Elizabeth Cao
Yvette Valenzuela
Dr. Sungho Jin, University of California, San Diego
Funding
Jacobs School of Engineering,
University of California, San Diego
Jacobs Retina Center,
University of California, San Diego
Dr. Warren Chang, University of Toronto
Whitaker Foundation
Quantum Dot Corporation, Hayward, California
Stein Institute for Research on Aging
Stupp Lab, Northwestern University
Prof. Samuel Stupp
Krista Niece
Dr. Elia Beniash
Dr. Jeff Hartgerink
Institute for Bionanotechnology in
Advanced Medicine,
Northwestern University
Kessler Lab, Northwestern University
Dr. Jack Kessler
Catherine Czeisler
Dr. Vijay Sarthy, Northwestern University