Improving Tissue Regeneration:

the Role of Nanoparticles in

Tissue Engineering
Ben Lawrence
Nanotechnology Course
12/1/07
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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,

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Concept of Tissue Regeneration

Transplant Cell isolation

Expand in
culture

Bioactive groups

porous scaffold
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Natural Matrices:
Small Intestinal Submucosa
 Predominantly type 1
collagen
 Degrades in 4 – 16 weeks
Serosa  Asymmetric porous
Muscle layer structure
Submucosa  Clinically used
 Urology
Mucosa  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
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Can the Microenvironment be
Improved?
 Custom tailor SIS for each tissue type
 Add targeted release of specific growth factors
 Modify SIS with Nanoparticles
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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

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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
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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
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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)
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Does Size Affect
Permeability?
Chamber 1
(C1) 16
Contains Urea 14

-4 cm/s)
12

Modified 10

SIS
Urea permeability (x10
8
*
6

Chamber 2 0
0 200 300 500
(C2) Size of latex spheres (nm)
Contains PBS
Mondalek, F.G., et al.: Biomaterials, (in press)
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Does Particle Concentration
Affect Permeability?
16  PLGA NPs
14
 300nm
-4 cm/s)

12

10
 Particle count
measured by
Urea permeability (x10

6 * flow cytometry
4

2
 1 mg/mL PLGA
0 = 1.6 x 108
0 0.1 1 5

Concentration of PLGA NPs (mg/ml) 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)
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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)
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Acknowledgements
 Fadee Mondalek  Brad Kropp
 H.K Lin  Brian Grady
 Sundar Madihally  K.M. Fung

 Funding from the Oklahoma Center for the

Advancement of Science and Technology (HR-
05-075) and the National Institute of Health
(1R21DK074858)
Questions?