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 Biology, Physiology, and Medicine Nanotechnology
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 Advancements in The fundamental chemistry, basic and clinical The integration physics, and materials neuroscience of the two science of nanotechnology
Neural Specific Bioactive Peptide Amphiphile Networks NH 2 OH O H H H H H H H O O O O O O O N N N N N N N N N N N N N OH O O O O O O O H H H H H H C 16 H 31 O-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 80 Live cells (%) 60 40 20 0 100 um 1 DIV 7 DIV 22 DIV 1 DIV 7 DIV 22 DIV Days in vitro Stupp Research Group, Northwestern University- Gabriel Silva
Neural Specific Bioactive Peptide Amphiphile Networks GFAP+ cells/ total number of cells (%) -tubulin+ cells/ total number of cells (%) 25 70 ** 60 20 50 15 * 40 30 10 20 * 5 10 0 0 1 DIV 7 DIV 1 DIV 7 DIV 1 DIV 7 DIV 1 DIV 7 DIV 1 DIV 7 DIV 1 DIV 7 DIV IKVAV-PA gel Laminin PDL 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 Funding Marie Davidson Jacobs School of Engineering, Smita Pathak University of California, San Diego Julie Schallhorn Elizabeth Cao Yvette Valenzuela Jacobs Retina Center, University of California, San Diego Dr. Sungho Jin, University of California, San Diego Whitaker Foundation Dr. Warren Chang, University of Toronto Quantum Dot Corporation, Hayward, California Stein Institute for Research on Aging Stupp Lab, Northwestern University Institute for Bionanotechnology in Prof. Samuel Stupp Advanced Medicine, Krista Niece Dr. Elia Beniash Northwestern University Dr. Jeff Hartgerink Kessler Lab, Northwestern University Dr. Jack Kessler Catherine Czeisler Dr. Vijay Sarthy, Northwestern University
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