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 Natural Matrices: Small Intestinal Submucosa Serosa Muscle layer Submucosa Predominantly type 1 collagen Degrades in 4 – 16 weeks Asymmetric porous structure Clinically used Mucosa 4 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 Can the Microenvironment be Improved? Custom tailor SIS for each tissue type Add targeted release of specific growth factors Modify SIS with Nanoparticles 5 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  NanoScience and Technology Institute, http://www.nsti.org/press/PRshow.html?id=2254 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 Nanoparticles FITC Labeled Fibroblasts Actin Stained 50 µm 7 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 8 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 Mondalek, F.G., et al.: Biomaterials, (in press) Just Right 10 Does Size Affect Permeability? Modified SIS Chamber 2 (C2) Contains PBS 16 Urea permeability (x10 -4 cm/s) Chamber 1 (C1) Contains Urea 14 12 10 * 8 6 4 2 0 0 200 300 Size of latex spheres (nm) Mondalek, F.G., et al.: Biomaterials, (in press) 500 Does Particle Concentration Affect Permeability? Urea permeability (x10 -4 cm/s) 16 14 PLGA NPs 12 10 8 * 6 4 2 0 0 0.1 1 5 Concentration of PLGA NPs (mg/ml) 11 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 Acknowledgements Fadee Mondalek H.K Lin Sundar Madihally Brad Kropp Brian Grady K.M. Fung Funding from the Oklahoma Center for the Advancement of Science and Technology (HR05-075) and the National Institute of Health (1R21DK074858) Questions?