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Improving Tissue Regeneration: the Role of Nanoparticles in Tissue Engineering

Improving Tissue Regeneration: the Role of Nanoparticles in Tissue Engineering. Ben Lawrence Nanotechnology Course 12/1/07. Organ Transplants. 98,074 are waiting for transplants as of 11/8/2007 17 deaths per day for people waiting on a transplant.

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Improving Tissue Regeneration: the Role of Nanoparticles in Tissue Engineering

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  1. Improving Tissue Regeneration: the Role of Nanoparticles in Tissue Engineering Ben Lawrence Nanotechnology Course 12/1/07

  2. Organ Transplants • 98,074 are waiting for transplants as of 11/8/2007 • 17 deaths per day for people waiting on a transplant From the www.unos.org, and http://www.transweb.org/qa/qa.htm,

  3. Concept of Tissue Regeneration Cell isolation Transplant Expand in culture Bioactive groups porous scaffold

  4. Serosa Muscle layer Submucosa Mucosa Natural Matrices:Small Intestinal Submucosa • Predominantly type 1 collagen • Degrades in 4 – 16 weeks • Asymmetric porous structure • Clinically used • Urology • Hernia (body wall) • Wound Healing • Commercially available • COOK SIS Raghavan D, Kropp BP, Lin H-K, Zhang Y, Cowan R, Madihally SV. Physical Characteristics Of Small Intestinal Submucosa Scaffolds Are Location-Dependent.  Journal of Biomedical Materials Research-Part A.  73A: 90–96, 2005

  5. Can the Microenvironment be Improved? • Custom tailor SIS for each tissue type • Add targeted release of specific growth factors • Modify SIS with Nanoparticles

  6. Nanocomposite Materials • World Market1 • 2006 - $33,700,000 • Projected 2013 - $144,600,000 • Wide variety of applications • Tissue engineering • Pharmaceuticals/drug delivery • Environmental • Catalysis [1] NanoScience and Technology Institute, http://www.nsti.org/press/PRshow.html?id=2254

  7. Nanoparticles FITC Labeled Fibroblasts Actin Stained 50 µm How do Nanoparticles Affect the System? • Particles protect growth factors • Enables targeted controlled release of growth factors • Uptake of nanoparticles by cells also helps in intracellular delivery

  8. How do Nanoparticles Affect Transport Properties? • Block small porous features, leave large features for cellular ingrowth • Change the system transport properties • Measured using permeability across scaffold

  9. Which size NPs? • Commercially available Latex particles • 2000 nm, 1000 nm, 500 nm, 300 nm, 200 nm, 50 nm 1000 nm 50 nm 300 nm Mucosal Serosal Too Big Too Small Just Right Mondalek, F.G., et al.: Biomaterials, (in press)

  10. Chamber 1 (C1) Contains Urea Modified SIS * Chamber 2 (C2) Contains PBS Does Size Affect Permeability? Mondalek, F.G., et al.: Biomaterials, (in press)

  11. * Does Particle Concentration Affect Permeability? • PLGA NPs • 300nm • Particle count measured by flow cytometry • 1 mg/mL PLGA = 1.6 x 108 particles/mL Mondalek, F.G., Lawrence, B.J., Kropp, B.P., Grady, B.P., Fung, K.-M., Madihally, S.V., and Lin, H.-K.: The incorporation of poly (lactic-co-glycolic) acid nanoparticles into porcine small intestinal submucosa biomaterials. Biomaterials, (in press)

  12. Summary • Nanoparticles can provide the controlled release of bioregulating signals to material • Material transport properties may be modified using nanoparticles • Modification shows promise in custom tailoring SIS for regenerating specific tissues Mondalek, F.G., Lawrence, B.J., Kropp, B.P., Grady, B.P., Fung, K.-M., Madihally, S.V., and Lin, H.-K.: The incorporation of poly (lactic-co-glycolic) acid nanoparticles into porcine small intestinal submucosa biomaterials. Biomaterials, (in press)

  13. Fadee Mondalek H.K Lin Sundar Madihally Brad Kropp Brian Grady K.M. Fung Acknowledgements • Funding from the Oklahoma Center for the Advancement of Science and Technology (HR-05-075) and the National Institute of Health (1R21DK074858)

  14. Questions?

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