Improving Tissue Regeneration: Improving Tissue Regeneration: the Role of Nanoparticles in the Role of Nanoparticles in

Tissue EngineeringTissue Engineering

Ben LawrenceBen Lawrence

Nanotechnology CourseNanotechnology Course

12/1/0712/1/07

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Organ TransplantsOrgan Transplants

98,074 98,074 are waiting for transplants as of 11/8/2007are waiting for transplants as of 11/8/2007 17 deaths per day for people waiting on a transplant17 deaths per day for people waiting on a transplant

From the www.unos.org, and http://www.transweb.org/qa/qa.htm,

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Cell isolation

Expand in culture

porous scaffold

Bioactive groups

Transplant

Concept of Tissue RegenerationConcept of Tissue Regeneration

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Submucosa

Serosa

Mucosa

Muscle layer

Natural Matrices:Natural Matrices:Small Intestinal SubmucosaSmall Intestinal Submucosa

Predominantly type 1 Predominantly type 1 collagencollagen

Degrades in 4 – 16 weeksDegrades in 4 – 16 weeks Asymmetric porous Asymmetric porous

structurestructure Clinically usedClinically used

UrologyUrology Hernia (body wall)Hernia (body wall) Wound HealingWound Healing

Commercially availableCommercially available COOK SISCOOK 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

5Can the Microenvironment be Can the Microenvironment be

Improved?Improved? Custom tailor SIS for each tissue typeCustom tailor SIS for each tissue type

Add targeted release of specific growth factorsAdd targeted release of specific growth factors Modify SIS with NanoparticlesModify SIS with Nanoparticles

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Nanocomposite MaterialsNanocomposite Materials

World MarketWorld Market11

2006 - $33,700,0002006 - $33,700,000 Projected 2013 - $144,600,000Projected 2013 - $144,600,000

Wide variety of applicationsWide variety of applications Tissue engineeringTissue engineering Pharmaceuticals/drug deliveryPharmaceuticals/drug delivery EnvironmentalEnvironmental CatalysisCatalysis

[1] NanoScience and Technology Institute, http://www.nsti.org/press/PRshow.html?id=2254

7How do Nanoparticles Affect the How do Nanoparticles Affect the

System?System? Particles protect growth factors Particles protect growth factors Enables targeted controlled release of Enables targeted controlled release of

growth factorsgrowth factors Uptake of nanoparticles by cells also helps Uptake of nanoparticles by cells also helps

in intracellular deliveryin intracellular delivery

50 µmFibroblasts

Actin Stained

NanoparticlesFITC Labeled

8How do Nanoparticles Affect How do Nanoparticles Affect

Transport Properties?Transport Properties? Block small porous features, leave large Block small porous features, leave large

features for cellular ingrowthfeatures for cellular ingrowth Change the system transport propertiesChange the system transport properties

Measured using permeability across scaffoldMeasured using permeability across scaffold

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Which size NPs?Which size NPs?

Too Big Too Small Just Right

1000 nm

Serosal

Mucosal

50 nm 300 nm

Commercially available Latex particlesCommercially available Latex particles 2000 nm, 1000 nm, 500 nm, 300 nm, 200 nm, 50 nm2000 nm, 1000 nm, 500 nm, 300 nm, 200 nm, 50 nm

Mondalek, F.G., et al.: Biomaterials, (in press)

10Does Size Affect Does Size Affect Permeability?Permeability?

Chamber 1(C1)

Contains Urea

Chamber 2(C2)

Contains PBS

Modified SIS

Size of latex spheres (nm)

0 200 300 500

Ure

a pe

rmea

bilit

y (x

10-4

cm

/s)

0

2

4

6

8

10

12

14

16

*

Mondalek, F.G., et al.: Biomaterials, (in press)

11Does Particle Concentration Does Particle Concentration

Affect Permeability?Affect Permeability? PLGA NPsPLGA NPs

300nm300nm Particle count Particle count

measured by measured by flow cytometryflow cytometry

1 mg/mL PLGA 1 mg/mL PLGA = 1.6 x 10= 1.6 x 1088 particles/mLparticles/mLConcentration of PLGA NPs (mg/ml)

0 0.1 1 5

Ure

a pe

rmea

bilit

y (x

10-4

cm

/s)

0

2

4

6

8

10

12

14

16

*

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)

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SummarySummary

Nanoparticles can provide the controlled Nanoparticles can provide the controlled release of bioregulating signals to materialrelease of bioregulating signals to material

Material transport properties may be Material transport properties may be modified using nanoparticlesmodified using nanoparticles

Modification shows promise in custom Modification shows promise in custom tailoring SIS for regenerating specific tailoring SIS for regenerating specific tissuestissues

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)

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AcknowledgementsAcknowledgements

Fadee MondalekFadee Mondalek H.K LinH.K Lin Sundar MadihallySundar Madihally

Brad Kropp Brad Kropp Brian Grady Brian Grady K.M. FungK.M. Fung

Funding from the Oklahoma Center for the Funding from the Oklahoma Center for the Advancement of Science and Technology (HR-Advancement of Science and Technology (HR-05-075) and the National Institute of Health 05-075) and the National Institute of Health (1R21DK074858)(1R21DK074858)

Questions?Questions?