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/ ,074 are waiting for transplants as of 11/8/ deaths per day for people waiting on a transplant 17 deaths per day for people waiting on a transplant From the and

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

4 Submucosa Serosa Mucosa Muscle layer Natural Matrices: Small Intestinal Submucosa Predominantly type 1 collagen Predominantly type 1 collagen Degrades in 4 – 16 weeks Degrades in 4 – 16 weeks Asymmetric porous structure Asymmetric porous structure Clinically used Clinically used Urology Urology Hernia (body wall) Hernia (body wall) Wound Healing Wound Healing Commercially available Commercially available COOK SIS 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, 2005Physical Characteristics Of Small Intestinal Submucosa Scaffolds Are Location-Dependent

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

6 Nanocomposite Materials World Market 1 World Market $33,700, $33,700,000 Projected $144,600,000 Projected $144,600,000 Wide variety of applications Wide variety of applications Tissue engineering Tissue engineering Pharmaceuticals/drug delivery Pharmaceuticals/drug delivery Environmental Environmental Catalysis Catalysis [1] NanoScience and Technology Institute,

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

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

9 Which size NPs? Too BigToo SmallJust Right 1000 nm Serosal Mucosal 50 nm300 nm Commercially available Latex particles Commercially available Latex particles 2000 nm, 1000 nm, 500 nm, 300 nm, 200 nm, 50 nm 2000 nm, 1000 nm, 500 nm, 300 nm, 200 nm, 50 nm Mondalek, F.G., et al.: Biomaterials, (in press)

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

11 Does Particle Concentration Affect Permeability? PLGA NPs PLGA NPs 300nm 300nm Particle count measured by flow cytometry Particle count measured by flow cytometry 1 mg/mL PLGA = 1.6 x 10 8 particles/mL 1 mg/mL PLGA = 1.6 x 10 8 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 Nanoparticles can provide the controlled release of bioregulating signals to material Material transport properties may be modified using nanoparticles Material transport properties may be modified using nanoparticles Modification shows promise in custom tailoring SIS for regenerating specific tissues 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 Fadee Mondalek H.K Lin H.K Lin Sundar Madihally Sundar Madihally Brad Kropp Brad Kropp Brian Grady Brian Grady K.M. Fung K.M. Fung Funding from the Oklahoma Center for the Advancement of Science and Technology (HR ) and the National Institute of Health (1R21DK074858) Funding from the Oklahoma Center for the Advancement of Science and Technology (HR ) and the National Institute of Health (1R21DK074858)

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