Wound Care: Needs and Challenges

Emergency application
Stop bleeding
Prevent infection
Provide barrier function
Restore volume/mass

Wound healing
Regenerate tissue
Limit scarring
Restore function

Challenges:
Antimicrobial cytotoxicity
Multidrug resistance of wound pathogens
Functional tissue restoration without scarring
1

Image credit:
http://biofilmbook.hypertextbookshop.com/v003/r002/contents/chapters/chapter003/section003/blue/page001.html

Worcester Polytechnic Institute

Bacterial Resistance

FDA: A
catastrophic
threat to
human
health

Plot Modified from: FDA Center for Drug Evaluation and

Research (CDER), 2013.

Worcester Polytechnic Institute

Antimicrobial Peptides (AMPs)

Naturally derived molecules
Stable, broad acting, and low likelihood of
development of microbial resistance

C-terminus

Surface tethering can reduce leaching,

proteolysis, and cytotoxicity

N-terminus

http://gonzalolira.blogspot.com

Worcester Polytechnic Institute

Cell-Derived Bioactive Scaffolds for Tissue Repair

Problems
Infection
Antimicrobial
concentration

Strategy

Outcomes

AMPs

Eliminate Infection

Tethered
AMPs

Increased
therapeutic dose

Tissue Loss
and Scarring

Matrix
Scaffold

Restore Tissue
without scarring

Antimicrobial
Cost

Cell
Factories

Reduce the cost of

peptide production
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Recombinant, Collagen-Bound Antimicrobial

Peptide: LL-37
G
FLA
p3x
FF
FF

LL

A
A

FF
LL

A
A

LL
G
G

A
A

Signal
Peptide

Cathelin
Prosequence

LL-37

F
F
L
L
A
A
G
G

CBD

G
G

Cathelicidin

G
G

Collagen

Prosequence

Cathelicidin cleaved
by proteinase-3

Collagen-Binding
Domain

LL-37
Antimicrobial Activity

Broad spectrum AMP

Protects against bacterial colonization

Prevents biofilm formation

Disrupts existing bacterial biofilms

Naturally expressed in the epidermis

Immunomodulatory activity

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AMP Designed for Functionality

TEI BioSciences, www.teibio.com

Organogenesis, Inc.,
www.organogenesis.com
Acell, Inc. www.acell.com

Gasper, R.; C.R. Miller. Localization, Concentration, and Antimicrobial Activity of

Human Cathelicidin LL-37 from H1299 Human Lung Carcinoma Cells to be Applied
to Dermal Wound Healing. 2013.

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Use LL37 Attached to Collagen for a Lasting Solution

(1)

(2)

(3)

(4)
1. Modify Cells
2. Tissue Culture

Key:

3. Decellularize
4. Cell-Derived Collagen
Scaffold

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Market Opportunity
Wound Care: $50 billion per year
Wound Care Products: $21 billion by 2015

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Wounds and Chronic Wounds by the Numbers

Wound care: $50 billion per year (on the rise)
20% of wounds become chronic
Wound infection: $24 billion per year; 100,000 deaths

Chronic Wounds: 7 million people per year have

a higher chance of infection due to constant
treatment and compromised tissue state.
Pressure/Diabetic Ulcers: 2 million people;
600,000 deaths
Cost up to $70,000 dollars per case

Burn Wounds: 1.1 million people; 50% mortality

Clark, R. A. F., Tissue Engineering for Cutaneous Wounds. Journal of
investigative dermatology 2007, 127 (5), 1018-1029.

Onaizi, S. A., Tethering antimicrobial peptides: Current status and potential

challenges. Biotechnology advances 2011, 29 (1), 67-74.

Worcester Polytechnic Institute

Transfected vs. Non-transfected Cells

H1299(-)CBD-LL37

H1299(+)CBD-LL37

No morphological differences
Indicates minimal toxicity due to protein production
10

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