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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

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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

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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)

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Model of Applied Nanotechnology to Medicine and Physiology

Nanoscience and Nanotechnology Biology, Physiology, and Medicine

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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.

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The Central Nervous System (CNS)

National Library of Medicine- www.nlm.nih.gov

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The Central Nervous System (CNS)

Gray’s Anatomy Online- http://www.bartleby.com

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The Central Nervous System (CNS)

Gray’s Anatomy Online- http://www.bartleby.com

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The Central Nervous System (CNS)

Gray’s Anatomy Online- http://www.bartleby.com

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The Central Nervous System (CNS)

Nature Encyclopedia- http://www.els.net

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The Cellular and Sub-Cellular Scales

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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
f local and systemic “side effects”

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The Successful Development Of CNS Nanotechnologies

Advancements in basic and clinical neuroscience Advancements in The fundamental chemistry, physics, and materials science of nanotechnology The integration

f the two

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Neural Specific Bioactive Peptide Amphiphile Networks

H N N H H N N H H N N H H N N H H N N H H N N H O O O O O O O O OH O O O O NH2 O H N OH O O

C16H31O-NH-AAAAGGGEIKVAV-COOH

Functional Peptide Region Spacer Region Hydrophobic Tail

Stupp Research Group, Northwestern University- Jeffery Hartgerink and Elia Beniash

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Stupp Research Group, Northwestern University- SEM by Dan Harrington

Neural Specific Bioactive Peptide Amphiphile Networks

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Stupp Research Group, Northwestern University- Gabriel Silva

Neural Specific Bioactive Peptide Amphiphile Networks

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Stupp Research Group, Northwestern University- Gabriel Silva

Neural Specific Bioactive Peptide Amphiphile Networks

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N NF

2 m

Neural Specific Bioactive Peptide Amphiphile Networks

Stupp Research Group, Northwestern University- Gabriel Silva

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Live cells (%) 20 40 60 80 100

1 DIV

PDL IKVAV-PA gel

7 DIV 22 DIV 1 DIV 7 DIV 22 DIV

Days in vitro

100 um

Neural Specific Bioactive Peptide Amphiphile Networks: Cell Viability/Cytotoxicity

Stupp Research Group, Northwestern University- Gabriel Silva

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-tubulin+ cells/ total number of cells (%) 10 20 30 40 50 60 70

1 DIV Laminin PDL IKVAV-PA gel 7 DIV

* **

1 DIV 7 DIV 1 DIV 7 DIV

GFAP+ cells/ total number of cells (%) 5 10 15 20 25 *

1 DIV Laminin PDL IKVAV-PA gel 7 DIV 1 DIV 7 DIV 1 DIV 7 DIV

Neural Specific Bioactive Peptide Amphiphile Networks

Stupp Research Group, Northwestern University- Gabriel Silva

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Nanoengineering Mesenchymal Stem Cells Differentiation into Photoreceptor Neurons

Silva Research Group, UCSD- Diana Yu and Mai Ho

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Nanoengineering Mesenchymal Stem Cells Differentiation into Photoreceptor Neurons

Silva Research Group, UCSD- Diana Yu and Mai Ho

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Functionalized Quantum Dot Targeting of Reactive Gliosis

Silva Research Group, UCSD- Smita Pathak

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Functionalized Quantum Dot Targeting of Reactive Gliosis

Silva Research Group, UCSD- Smita Pathak and Julie Schallhorn

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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

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Functionalized Quantum Dot Targeting of Reactive Gliosis

Silva Research Group, UCSD- Julie Schallhorn

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Functionalized Quantum Dot Targeting of Reactive Gliosis

Silva Research Group, UCSD- Julie Schallhorn and Smita Pathak

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URL: www.silva.ucsd.edu Email: gsilva@ucsd.edu

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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
Dr. Warren Chang, University of Toronto

Quantum Dot Corporation, Hayward, California Stupp Lab, Northwestern University

Prof. Samuel Stupp

Krista Niece

Dr. Elia Beniash
Dr. Jeff Hartgerink

Kessler Lab, Northwestern University

Dr. Jack Kessler

Catherine Czeisler

Dr. Vijay Sarthy, Northwestern University

Funding Jacobs School of Engineering, University of California, San Diego Jacobs Retina Center, University of California, San Diego Whitaker Foundation Stein Institute for Research on Aging Institute for Bionanotechnology in Advanced Medicine, Northwestern University