Slide 1

Report
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

[1] 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?

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