1. NANOPARTICLES FOR IMPROVED SKIN
WOUND HEALING
Faculty Mentors: Dr. Berthiaume and Dr. Sofou
Graduate Student Mentors: Melissa Przyborowski,
Michelle Sempkowski and Trevan Locke
Group Members: Thomas Chedid, Abhinav Damaraju,
Yunqi He, Anthony Yung

2. Problem and Need Statements
PROBLEM
● Chronic wounds →
• significant economic and health care
burden in the US
● Current wound healing solutions →
• expensive
• do not target exact mechanism of
impaired healing in diabetic/elderly
patients.
NEED
● Develop a cost-effective solution that addresses the underlying wound
healing response of diabetic and elderly patients so that healing rates
can be increased efficiently.

3. Significance and Benefits
Financial significance: Huge market, High demand!
X =
Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT. Human skin wounds: a major and
snowballing threat to public health and the economy. Wound Repair Regen. 2009;17:763–71.
$10,376
(Avg. cost/wound)2.5 M Treated Annually
$26 billion
Annual US Spending
Reduction in healing time by 2 weeks → ~$10.4 billion in savings
Benefits to society:
➢Improve current state of health care for diabetic/elderly patients
➢Enhance appearance of wounds
➢Minimize pain by healing faster
➢Less amputations due to chronic wounds

4. Current Technologies
Treatment Company Pros Cons
Vacuum assisted
closure
Kinetic
Concepts (KCI)
Provides a sealed
environment for wound to
heal and minimize
bacterial infection
Expensive
Dermal substitutes
(Dermagraft®)
Shire
Regenerative
Medicine
Stimulate healing process
by using human fibroblast,
growth factors, proteins,
and cytokines
Only ~50% effective
Platelet-derived growth
factor (Regranex®)
Smith &
Nephew
Promotes healing Potentially
carcinogenic
Mesenchymal stem
cells (MSCs)
Various (not
FDA approved)
Secret proteins to promote
healing
Viability/storage
issues
Nanoparticle (Our
solution)
-- Minimizes proteolytic
degradation
Controlled release
over long period of
time
Preclinical studies
show wounds close 1
week earlier
Application
method unclear

5. Key Criteria
Key
Criteria
Reduce
Healing
RateSimilar to
Current
Standard of
Care
Convenient
Application
Minimal
Side Effect
Cost
Effective

6. Proposed Concept: Utilization of
Nanoparticles
KEY POINTS:
• Nanoparticles = inhibitors
• Growth factor controlled release
• Further penetration of growth factors
• Long-term stimulation of cell growth

7. Is it worth it?
Scientific risk:
● LOW:
–Pre-clinical studies on nanoparticles for improved wound healing have
already shown effectiveness [1]
Business risk:
● LOW:
–Our solution can be easily combined with other, existing means for
wound healing.
Cost risk:
● MODERATE:
–$50,000 for pre-clinical studies
–high cost of clinical trials, but market is very large → large ROI
1. Przyborowski, M. Strategies for Improving Growth Factor Function in Diabetic Wounds. 2012, July 18.
Overall: Considering the high demand in diabetic/elderly patients
and the relatively low risks, the possible health benefits of the project
outweigh the potential cost of production.

8. Prototype
1. Synthesis of the nanoparticles
1. Tests to determine if the nanoparticles have the correct
size and if linkage indeed occurred.
1. Mathematical model of the diffusion of the
nanoparticles into the wound environment.

9. Methods
• Nanoparticles made using a combination of peptides and lipids:
– DSPC+Cholesterol+DSPA used to form liposomes
– Deca-lysine is then attached
• DLS assay performed on nanoparticles to find the average size.
• Size Exclusion Chromatography with fluorescence assays performed on
nanoparticles with and without the peptide attached
• Mathematically modeled the diffusion of nanoparticles into the wound.

10. Diffusion of a Solute from a Polymeric Material
- Using a Fick’s Second Law of Diffusion
-A solute is uniformly distributed within microporous polymeric disc of
radius R and thickness L. All of the surfaces of the disc are coated with
an impermeable material except for the surface located at x=L
Modeling

11. Modeling Results
- Analytical Solution:

12. Modeling Results
- Numerical Solution:
• Source term was added to simulate release of growth factors from nanoparticles into
wound environment

13. - Numerical Solution:
• Three separate half-life cases were evaluated/modeled to determine
concentration profile
Modeling Results
1 HOUR 1 DAY
1 WEEK

14. Experimental Results
Dynamic Light Scattering (DLS ) Assay:
● 2 sets of data
● Empty liposomes: 100 nm – 140 nm
● Liposomes with peptide: >1000 nm
Significance:
● Size of empty liposome is around size of skin pores à diffusion
possible
● other?

15. Experimental Results
Size Exclusion Chromatography
Significance:
• Empty liposome aggregation undetected with DLS
• Peptide does attaches to liposomes

16. ● Assess stability and dissociation rate of nanoparticles in
a wound-like environment through the addition of a
high concentration of protease.
● Assess biological activity of growth factor in nanoparticle
● Perform in vivo experiments

17. Special Thanks to:
Experts: Dr. Berthiaume, Dr. Sofou, Dr. Henry Hsia,
Melissa Przyborowski, Michelle Sempkowski