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Hyaluronic Acid Scaffolds for Neural Tissue Engineering

Hyaluronic Acid Scaffolds for Neural Tissue Engineering. Shalu Suri April 2009. Department of Biomedical Engineering The University of Texas at Austin. Hyaluronic acid. Ubiquitous ECM component Cartilage and synovial fluid Non-immunogenic Multiple sites for modification hydroxyl

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Hyaluronic Acid Scaffolds for Neural Tissue Engineering

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  1. Hyaluronic Acid Scaffolds for Neural Tissue Engineering Shalu Suri April 2009 Department of Biomedical Engineering The University of Texas at Austin

  2. Hyaluronic acid • Ubiquitous ECM component • Cartilage and synovial fluid • Non-immunogenic • Multiple sites for modification • hydroxyl • carboxyl • acetamido • Enzymaticallydegradable Hyaloid (vitreous) +Uronic acid Isolated first in 1934

  3. Role in Wound Repair and angiogenesis • Plays an important role in wound repair • Inflammation, granulation, repair, remodeling • Participates in angiogenesis when degraded in small fragments • 500 – 8000 Da

  4. Adapted from JB Leach Dissertation

  5. Nerve Structure www.backpain-guide.com/.../10-1_Nerve_Struct.jpg

  6. Current Clinical Treatments End to End reconnection causesTension Autologous nerve graft Schmidt and Leach, Ann Rev BME, 2003

  7. Design of Nerve Guidance Conduit Channels Bellamkonda, Biomaterials, 2007

  8. Digital Micromirror Device (DMD) Lu et al., JBMR, 2006 Developed by Yi Lu and Dr. ShaoChen Chen

  9. Fabrication using Digital Micromirror Device (DMD) Han et al, 2008 Lu et al, JBMR-A, 2006

  10. HA scaffolds of DMD a) b) c) d)

  11. 3D Scaffold ?? • HA scaffolds are soft • Water absorption • Difficult to create long 3D scaffolds using layer by layer fabrication • Addition of acrylated salts • Zinc acrylate

  12. “Designer Scaffolds” • Scaffolds with structures mimicking native architecture • Branched Scaffolds • Multi lumen conduits • Growth factors gradient • Nerve growth factor gradient ? • Multiple gradients running in opposite directions • Permissive cues • Inhibitory cues

  13. Growth factors • Support the regeneration of axons • NGF,BDNF, neurotropin-3, neurotrophin-4/5, GDNF, FGF, PDGF, VEGF, CNF, and IGF-I • Agarose scaffolds with laminin gradient – enhanced neurite extension from DRGs • NGF gradient – guide neurite growth Cao et al, Neuroscience 2003

  14. Branched conduit Scale bars 500 µm

  15. XPS analysis Unwashed washed in PBS (pH 4)

  16. Cytocompatibility and Cell Proliferation

  17. Hyaluronan retains bioactivity top middle bottom negative Scaffold was incubated with biotinylated HA-binding protein and stained for PE-streptavidin

  18. Collagen conjugation and cell attachemnt

  19. Gradient Scaffold

  20. Summary • Optimization of the fabrication technique to create HA scaffold • Successfully created 3D scaffold with defined architecture • “Designer scaffolds” • Multi lumen • Gradient

  21. What Next ?? • Create NGF gradient • Study the feasibility of gradient with DRGs • Create other designer architectures • Multiple gradients with in single scaffolds

  22. SEM 10 µm

  23. Final goal Bioactive scaffold composed of Native ECM components and cells with neural architecture for Neural tissue engineering

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