Composite Poly(methyl methacrylate)/Poly(ethylene glycol) electrospun nanofibrous mats as a novel wound dressing for controlled release of an anti-

scarring agent

Malihe-Sadat Poormasjedi-Meibod, PhD candidate

Experimental medicine

Burn and Wound Healing Lab, Dep. Of Surgery

University of British Columbia

March 16th, 2015

Background-Wound healing process

Background-Wound healing spectrumWound healing spectrum

Normal wound healing Non-healing wounds1. Diabetic foot ulcer 2. Pressure ulcer

Post-burnhypertrophic scars

3

Skin fibrosis

Background-HSC current treatments

4

4

Background-KynA as an anti-fobrogeic agentA

C 6.25 12.5 25 50 100 150 (µg/ml)

β-actin

Collagen-I

KynA

MMP1

Normal Control Vehicle

10x

2x

KynA

0 12 240

40

80

120

160

Con

KA

Time: Hours

Nu

mb

er

of

mig

rati

ng

fi

bro

bla

sts

0 36 72 1080

40

80

120

160

Con

KynA

Fib

rob

las

t to

tal c

ell

nu

mb

er

(X1

00

0)

B

C

Poormasjedi-Meibod et al., PLOSone, 2014

**

**

Hypothesis

KynA can be incorporated into nanofibers to develop anti-fibrogenic wound dressings which slowly release the drug and improve the wound healing

outcome.

Electrospinning process and parameters

Polymer PEG 1KD(W/W%)

Voltage(kV)

Syringe pump (mm/min)

KynA(W/W%)

Solvent

PMMA (350 KD) 0 24 0.1 6 DMF

PMMA (350 KD) 1 24 0.1 6 DMF

PMMA (350 KD) 2.5 24 0.07 6 DMF

PMMA (350 KD) 5 24 0.07 6 DMF

PMMA (350 KD) 10 24 0.05 6 DMF

PMMA (350 KD) 20 24 0.05 6 DMF 7

Electrospinning. Current approaches to electrospun nanofibers for tissue engineeringNae Gyune Rim et al 2013 Biomed. Mater. 8 014102 doi:10.1088/1748-6041/8/1/014102

SEM images of PMMA-PEG nanofibers

10% 20%1% 2.5% 5%

PEG

1K

5K

10K

PMMA

Dressing’s hydrophobicity and wetting

1 2 5 10 20 300

2

4

6

8

10

12PMMA+10% PEG

PMMA

Time: Minutes

We

igh

t g

ain

e

(% o

f th

e d

res

sin

g w

eig

ht)

9

PMMA PMMA+10%PEGA

B

Release study in PBS, total immersion setting

A

0 20 40 60 80 100 1200

10

20

30

40

50

60

70

80

90

100

PMMA

1% PEG

2.5% PEG

5% PEG

10% PEG

20% PEG

Time: hours

Cu

mu

lati

ve

Ky

nu

ren

ic A

cid

Re

lea

se

(% L

oa

de

d)

10

Release study is PBS, 2 chamber well setting

10 30 50 70 90 1100

10

20

30

40

50

60

70

PMMA+20% PEG

PMMA+10% PEG

PMMA+5% PEG

Time: Hours

Cu

mu

lati

ve

Ky

nu

ren

ic A

cid

re

lea

se

(%

of

tota

l lo

ad

ed

dru

g)

B

11

A

PBS

Hydrogel

NF+KynA

B

0 36 72 1080

40

80

120

160

200Control

NF

NF+KynA

KynA

Time:Hours

Fib

rob

las

t n

um

be

r (X

10

00

)

** **

**

**

**

Assessment of medicated mat’s cytocompatibility

12

Control NF NF+ KynA

FibroblastsC

Eth

idiu

m h

om

od

ime

r

Calcein

KynA

Dermal fibroblast

NF+KynA DMEM media

A

Dressing’s biological activity assessment

Con NF NF+KynA KynA0

20

40

60

80

100

120

140

160

180

200

MM

P1

/GA

PD

H(%

of

co

ntr

ol)

* *

Con NF NF+KynA KynA0

20

40

60

80

100

120

Co

llag

en

-I/G

AP

DH

(% o

f c

on

tro

l) ** **

A

Col-I

GAPDH

Con NF NF+KynA KynA

MMP1

13

B C

10x

2xA Normal Control NF NF+KynA

KynA cream

14

KynA-loaded dressings reduces skin fibrosis

Nor Con NF NF+Kyn Kyn Cream

0

5

10

15

20

25

30

35

40

MM

P-1

/GA

PD

H m

RN

A

ex

pre

ss

ion

fo

ld c

ha

ng

e

**

**

A

NF+KynA KynA cream Nor

Con NF

NF+Kyn

Kyn C

ream

0

5

10

15

20

25

Co

l-I/G

AP

DH

mR

NA

e

xp

res

sio

n f

old

ch

an

ge

****

B

Nor Con NF NF+KynA KynA cream

Conclusion

PMMA+10% PEG nanofibers can be used as an effective slow releasing drug delivery system for KynA.

Nanofiber-released KynA effectively modulates the expression of ECM components in vitro and in vivo.

Application of KynA-loaded nanofibers can improve the wound healing outcome in patients prone to develop skin fibrosis.

Dr. Aziz GhaharySanam SalimiDr. Layla NabaiRyan HartwellDr. Reza JaliliDr. Yunyuan Li Dr. Ruhi Kilani

Acknowledgements

16

Collaborators:Dr. Hellen Burt

John JacksonDr. Frank Ko

Victor LeungDr. Emma Guns

Dr. Azadeh TabaDr. Yun ZangAli FarokhiDr. Mohsen KhosraviDr. Saman Pakyari

Thank you for your attention!