1. Tis s u e
E n g in e e r in g o f
S k in
CHE 554: Principles of
Tissue Engineering
11/10/08
Aditya Shah
Karthik Gopalakrishnan
2. T is s u e E n g in e e r in g o f S k in
O v e r v ie w
• In t r o d u c t io n
• A n a t o m y o f t h e s k in
• R o le o f T i s s u e E n g in e e r i n g
• A p p lic a t io n s
• C o m m e r c ia l A s p e c t s
• C h a lle n g e s
• Fu tu re
• C o n c lu s io n
• Re fe re n c e s
3. T is s u e E n g in e e r in g o f S k in
In t r o d u c t io n
4. T is s u e E n g in e e r in g o f S k in
• Th e a i m o f s k in e n g i n e e r in g is to c re a te
a f u n c t io n a l b i o lo g ic a l s u b s t it u t e to
r e s t o r e h o m e o s t a s is o f t h e b o d y
• Us e of f u n d a m e n t a ls of m e d i c in e ,
b io lo g y , e n g in e e r in g a n d b i o t e c h n o lo g y
• A p p r o x im a t e ly 5 0 0 , 0 0 0 s u r g ic a l
p r o c e d u r e s p e r f o r m e d e v e r y y e a r in t h e
U .S .
5. T is s u e E n g in e e r in g o f S k in
• G o ld s t a n d a r d a p p r o a c h w a s w id e ly u s e d
b e f o r e t h e in t r o d u c t io n o f t h e Tis s u e
E n g in e e r e d S k in
• C u r r e n t ly a v a ila b le s k in s u b s t i t u t e s ,
in c lu d e : a u t o g r a f t s , a ll o g r a f t s , x e n o g r a f t
a n d s y n t h e t ic m a t e r i a ls t h a t a r e b e in g
im p la n t e d .
• T h e u s e o f g r a f t s is v e r y i m p o r t a n t
6. T is s u e E n g in e e r in g o f S k in
A n a t o m y o f T h e S k in
8. T is s u e E n g in e e r in g o f S k in
• S k in - L a r g e s t o r g a n o n t h e h u m a n b o d y .
• A c c o u n t s f o r 1 5 % o f t h e b o d y w e ig h t a n d
is m o r e t h a n t h e w e ig h t o f t h e s in g le
in t e r n a l o r g a n o f t h e b o d y .
• A s p e c ia l f ie l d o f s t u d y D e r m a t o lo g y is
u s e d t o s t u d y t h e n a t u r e o f t h e s k in a n d
it s b e h a v io r .
9. T is s u e E n g in e e r in g o f S k in
S k in is c o m p o s e d o f t h r e e la y e r s
3. E p i d e r m is : T h e o u t e r m o s t la y e r
5. D e r m i s : T h e m id d l e la y e r
3 . H y p o d e r m is : T h e lo w e r m o s t l a y e r
10. T is s u e E n g in e e r in g o f S k in
E p id e r m is
• T h e o u t e r m o s t la y e r
• F o r m s t h e p r o t e c t iv e w r a p o v e r t h e
b o d y’ s s u rfa c e .
• D o e s n o t h a v e b lo o d v e s s e ls
• N o u r is h e d b y d if f u s io n f r o m t h e d e r m i s
• E p id e r m i s is s u b d iv id e d in t o 5 la y e r s :
1. S tra tu m c o rn e u m
2. S t r a t u m lu c id u m
3. S t r a t u m g r a n u lo s u m
4. S t r a t u m s p in o s u m
5. S t r a t u m g e r m in a t iv u m
11. T is s u e E n g in e e r in g o f S k in
• T h e m a in t y p e o f c e lls a r e
k e r a t in o c y t e s , m e la n o c y t e s , la n g e r h a
n s c e lls a n d M e r k e l c e lls .
• M e la n o c y t e s - P r o d u c e s m e la n in
w h ic h g iv e s s k in it s c o lo r a n d
p ro te c ts fro m th e h a rm fu l UV
r a d ia t io n
• k e r a t in o c y t e s , P r o d u c e s k e r a t in
w h ic h is a w a t e r r e p e lle n t b o d y
w h ic h g iv e s t h e e p id e r m is it s
s tre n g th .
12. T is s u e E n g in e e r in g o f S k in
D e r m is
• V a r ie s in t h i c k n e s s a c c o r d in g t o l o c a t io n
• T h r e e t y p e s o f t is s u e s :
4. C o lla g e n
5. E la s t ic t is s u e
6. R e t ic u la r f ib e r s
• T w o la y e r s o f D e r m is :
P a p illa r y : h a s t h in a rra n g e m e n ts o f c o l la g e n
f ib e r s .
R e t ic u la r la y e r s : t h i c k e r t h a n p a p i lla r y la y e r .
13. T is s u e E n g in e e r in g o f S k in
S p e c i a liz e d c e l ls o f D e r m is h a s :
• H a ir f o lli c le s
• S e ba c e o us ( o il ) g la n d s a nd a p o c r in e
( s c e n t ) g la n d s
• A l s o c o n t a in s e c c r in e ( s w e a t ) g la n d s but
a r e n o t a s s o c i a t e d w it h h a ir f o llic le s .
• B lo o d v e s s e ls a n d n e rv e s ha s a n e tw o rk
t h r o u g h t h i s la y e r .
• Th e n e rv e t r a n s m it s s e n s a t io n s o f to u c h ,
p r e s s u r e , p a in , it c h a n d t e m p e r a t u r e .
14. T is s u e E n g in e e r in g o f S k in
H y p o d e r m is
• Ha s la y e r of fa t a nd c o n n e c t iv e t is s u e
th a t ho us e s la r g e r b lo o d v e s s e ls a nd
n e rv e s .
• Th e s iz e o f t h is la y e r v a r ie s th ro u g h o u t
th e b o d y a n d fro m p e rs o n to p e rs o n .
• Im p o r t a n t in th e r e g u la t io n of
te m p e ra tu re of th e s k in it s e lf a nd th e
b o d y.
15. T is s u e E n g in e e r in g o f S k in
F u n c t io n s o f s k in
• T o m a in t a in h o m e o - s t a s i s o f t h e b o d y .
• T o p r o v i d e p r o t e c t io n , s e n s a t io n ,
a b s o r p t io n , s t o r a g e a n d s y n t h e s is ,
e x c r e t io n , h e a t r e g u la t io n , c o n t r o l
e v a p o r a t io n o f b o d y f lu id s .
16. T is s u e E n g in e e r in g o f S k in
R o le o f T is s u e
E n g in e e r in g
17. T is s u e E n g in e e r in g o f S k in
W h y d o w e n e e d E n g in e e r e d S k in t o
p ro g re s s ?
• P r o m o t e w o u n d h e a li n g
• M o d e r a t e t h e p a in d u e t o w o u n d
• H i g h e r r a t e o f c e ll p r o lif e r a t i o n in in v i t r o
c u lt u r e
• O p t i m u m u s e o f b io m a t e r ia ls a n d f ie l d
a lli e d t o it
• T e c h n o lo g y a v a il a b le t o p a t ie n t s e a s ily
• B e t t e r q u a li t y o f lif e f o r p a t i e n t
• A f f o r d a b le
18. T is s u e E n g in e e r in g o f S k in
M a in P r in c ip le s o f T i s s u e E n g in e e r in g
• T h e c e ll s o u r c e is id e n t if ie d , s e p a r a t e d
a n d a ls o p r o d u c e d in a m p le n u m b e r s
• T h e a lt e r n a t i v e b io c o m p a t ib le m a t e r ia l
w h ic h c o u ld b e u s e d a s a c e ll s u b s t r a t e
o r c e ll e n c a p s u la t io n m a t e r ia l is o la t e d o r
s y n t h e s iz e d
• T h e c e lls s e e d e d o r o n t o t h e m a t e r ia l
m u s t m a in t a in t h e e x a c t f u n c t i o n ,
m o r p h o lo g y
• T h e e n g in e e r e d s t r u c t u r e is t h e n p la c e d
in t o t h e a p p r o p r ia t e in v i v o s it e
19. T is s u e E n g in e e r in g o f S k in
P ro c e s s
• S t a r t b u ild i n g m a t e r ia l
• S h a p e t h e m a t e r ia l
• S e e d it w it h liv in g c e ll s
• B a t h e it w i t h g r o w t h f a c t o r s
• C e lls m u lt ip ly & f i ll u p t h e s c a f f o ld & g r o w
in t o t h r e e - d im e n s io n a l t is s u e
• Im p la n t e d in t h e b o d y
• C e lls r e c r e a t e t h e i r in t e n d e d t i s s u e
f u n c t io n s
• B lo o d v e s s e ls a t t a c h t h e m s e lv e s t o t h e
n e w t is s u e
• T h e s c a f f o ld d is s o lv e s
• T h e n e w ly g r o w n t is s u e e v e n t u a l ly b le n d s
in w it h it s s u r r o u n d in g s
20. T is s u e E n g in e e r in g o f S k in
S c a f f o ld s
P r o p e r t ie s o f S c a f f o ld s
• S t r u c t u r a l In t e g r it y
• E x a c t p o r e s iz e
• M e c h a n ic a l s t r e n g t h
• B io d e g r a d a b le
21. T is s u e E n g in e e r in g o f S k in
S y n t h e s is o f T is s u e E n g in e e r e d S c a f f o ld s
Me th o d s
• N a n o f i b e r S e lf - A s s e m b ly
• T e x t il e t e c h n o lo g ie s
• S o lv e n t C a s t in g & P a r t ic u l a t e L e a c h in g
(S C P L )
• G a s F o a m in g
• E m u ls if ic a t io n / F r e e z e - d r y in g
• T h e r m a lly In d u c e d P h a s e S e p a r a t i o n
( T IP S )
22. T is s u e E n g in e e r in g o f S k in
M a t e r ia ls u s e d f o r m a k in g S c a f f o ld s
N a tu ra l
• C o lla g e n
• F ib r o n e c t in
• G e la t in
S y n t h e t ic
• P E G T p o ly ( e t h y le n e g ly c o l
t e r e p h t h a la t e )/ P B T p o ly ( b u t y le n e
t e r e h t h a la t e )
• P L G A p o ly ( D l - la c t id e - c o - g ly c o lid e )
B io S y n t h e t ic
• C o lla g e n w it h a m n io t ic m e m b r a n e
c o mpo ne nt
•
23. T is s u e E n g in e e r in g o f S k in
C o lla g e n
• S y n t h e s iz e d b y F ib r o b la s t s a n d
M y o f i b r o b la s t s
• P r e s e n t i n D e r m is
24. T is s u e E n g in e e r in g o f S k in
T y p e s o f C o lla g e n
• T y p e I C o lla g e n - T h e m o s t a b u n d a n t
c o lla g e n in t h e b o d y . F o u n d in t e n d o n s ,
b o n e s , s k i n a n d o t h e r t is s u e s .
P a r t ic u la r ly a b u n d a n t in t h e s c a r t is s u e .
• T y p e s II , IX , X , X I - C a r t il a g e
• T y p e III - C o m m o n in f a s t g r o w in g t is s u e ,
p a r t ic u la r ly a t t h e e a r ly s t a g e s ( P h a s e 1 )
o f w o u n d r e p a ir . M u c h o f it i s r e p la c e d
la t e r b y t h e t y p e s t r o n g e r a n d t o u g h e r
25. T is s u e E n g in e e r in g o f S k in
• T y p e IV - B a s a l la m in a ( f ilt r a t io n
m e m b r a n e o f c a p il la r ie s )
• T y p e V , V I - G e n e r a lly f o u n d a l o n g s id e
typ e I
• T y p e V II - E p it h e li a ( lin in g o f G I t r a c t ,
u r in a r y t r a c t , e t c . )
• T y p e V III - L i n i n g o f b lo o d v e s s e ls
• T y p e X II - F o u n d a l o n g s id e a n d in t e r a c t s
w it h t y p e s I a n d III
26. T is s u e E n g in e e r in g o f S k in
F ib r o n e c t in
• F ib r o n e c t in is m a jo r m u l t i f u n c t io n a l
c o m p o n e n t o f th e EC M
• W h ile D e s ig n in g a f u l ly f u n c t io n a l s k i n t h e
m a jo r c o n s id e r a t io n is a bo ut th e
m e c h a n ic a l fo rc e s a nd in t e r a c t io n s
b r o u g h t a b o u t b y w o u n d c o n t r a c t io n
• W o u n d c o n t r a c t io n in v o lv e s a c o m p l e x
in t e r p la y b e tw e e n th e f ib r o b la s t
c y t o s k e le t o n a n d i n t e g r i n s w it h t h e ir E C M
lig a n d s
• M e c h a n ic a l s t r e t c h in g a f f e c t s f i b r o n e c t i n
f u n c t io n
• F ib r in , a s s o c ia t e d w i t h f ib r o n e c t in , h a s
b e e n s h o w n t o s u p p o r t k e r a t in o c y t e a n d
f i b r o b la s t g r o w t h b o t h in v it r o a n d in v iv o ,
27. T is s u e E n g in e e r in g o f S k in
P E G T/P B T/P LG A
• N o n T o x ic
• B io d e g r a d a t io n c o u ld b e in c r e a s e d
28. T is s u e E n g in e e r in g o f S k in
D T B P C r o s s li n k e d
C H IT O S A N
• C h it o s a n is
d e a c e t y la t e d d e r iv a t iv e
o f c h it in
• Im p r o v e d t e n s ile
s t r e n g t h w it h 8 0 &
9 0 % c h it o s a n
• Im p r o v e d p o r o s it y
w it h c r o s s lin k e d D T B P
• Re d uc e d a nd
im p r o v e d
b io d e g r a d a t io n r a t e
29. T is s u e E n g in e e r in g o f S k in
A p p lic a t io n s
30. T is s u e E n g in e e r in g o f S k in
A r e a s w h e r e T is s u e E n g in e e r i n g o f S k in c a n
be us e d
3. D ia b e t i c s o r e s a n d u lc e r s
5. H e a lin g a n d r e p la c e m e n t o f b u r n e d s k in
7. R e d u c t i o n in s c a r f o r m a t io n
9. P la s t ic / C o s m e t ic S u r g e r y
31. T is s u e E n g in e e r in g o f S k in
D ia b e t ic s o r e s
a n d u lc e r s
• D i a b e t ic s o r e s
a c c o u n t s f o r a lm o s t
5 0 % o f t o t a l p a t ie n t s
a d m it t e d t o h o s p it a l s
f o r d ia b e t ic r e la t e d
p r o b le m s
• N e rv e d a m a g e c a n
32. T is s u e E n g in e e r in g o f S k in
• D a m a g e d to n e rv e s
le a d s t o le s s o x y g e n
a n d b lo o d c ir c u la t io n in
th e a ffe c te d a re a
• In ju r ie s c o m m o n ly
le a d t o in f e c t io n o r
g a n g re n e
• H ig h in f e c t io n m a y
le a d t o a m p u t a t io n o f
t h e in f e c t e d p a r t
33. T is s u e E n g in e e r in g o f S k in
T r e a t m e n t s f o r D ia b e t ic U lc e r s
• A n t ib io t ic s - N it r ic o x id e is b e in g
in v e s t ig a t e d a s it is a p o w e r f u l
v a s o l id a t o r
• A n t ib io t ic s c a n b e u s e d t o r e d u c e t h e
p u t r i d s m e ll o f in f e c t i o n
• U s e o f lig h t t h e r a p y
34. T is s u e E n g in e e r in g o f S k in
• A d v a n c e d d r e s s in g
t e c h n iq u e s u s in g
s y n t h e t ic D r e s s in g ,
b io lo g ic a l d r e s s in g , b io -
s y n t h e t ic d r e s s in g o r
c u lt u r e d k e r a t in o c y t e
d r e s s in g
35. T is s u e E n g in e e r in g o f S k in
B u rn s
• A p p r o x im a t e ly
2 , 1 5 0 , 0 0 0 p a t ie n t s a r e
t r e a t e d in t h e U . S a lo n e
f o r b u r n r e la t e d
c o m p lic a t io n s
• S e r io u s n e s s o f a b u r n
in ju r y d e p e n d s o n h o w
d e e p t h e in ju r y is a n d
h o w m u c h o f th e b o d y
36. T is s u e E n g in e e r in g o f S k in
D e g re e s o f B u rn s
• F ir s t d e g r e e b u r n s
a f f e c t t h e o u t e r la y e r o f
t h e s k in , c a u s in g p a in ,
r e d n e s s , a n d s w e llin g .
• In ju r y t o t h e s e c o n d
la y e r o f s k in ( t h e
d e r m is ) is c a lle d
s e c o n d d e g re e b u rn s .
• T h ir d - d e g r e e b u r n s
e x t e n d in t o d e e p e r
t is s u e s , c a u s in g b r o w n
37. T is s u e E n g in e e r in g o f S k in
Tr e a t m e n t f o r B u r n s
• T w o m a jo r t y p e s o f S u r g ic a l P r o c e d u r e s
t h a t c a n h e l p t o c o n c e a l s c a r r in g a n d
r e p la c e lo s t t i s s u e f o r s e v e r e b u r n
v ic t im s :
6. D e r m a b r a s io n .
8. S k in G r a f t s .
38. T is s u e E n g in e e r in g o f S k in
• D e r m a b r a s io n is a
s u r g ic a l p r o c e d u r e t o
im p r o v e o r m in im iz e t h e
a p p e a ra n c e o f s c a rs ,
r e s t o r e f u n c t io n a n d
c o r r e c t d is f ig u r e m e n t
r e s u lt in g f r o m a n in ju r y .
39. T is s u e E n g in e e r in g o f S k in
• A S k in G r a f t is
s u r g ic a l p r o c e d u r e in
w h ic h a p ie c e o f s k in
fro m o n e a re a o f th e
p a t ie n t ' s b o d y is
t r a n s p la n t e d t o a n o t h e r
a re a o f th e b o d y.
• Ty p e s o f g r a f t s
a v a ila b le :
P in c h g r a f t s
S p lit - t h ic k n e s s g r a f t s
F u ll t h ic k n e s s g r a f t s
40. T is s u e E n g in e e r in g o f S k in
S c a rs
Th r e e t y p e s o f s c a r s
• K e lo id
• H y p e r t r o p h ic
• C o n tra c tu re s
41. T is s u e E n g in e e r in g o f S k in
K e lo id s c a r s
• S c a r s w ill g r o w
b e y o n d t h e s it e o f in ju r y
• Th e y o c c u r w h e n t h e
b o d y c o n t in u e s t o
p r o d u c e c o lla g e n a
t o u g h f ib r o u s p r o t e in ,
a fte r th e w o u n d h a s
h e a le d .
• C e ll t y p e t e r m e d
f ib r o c y t e w it h a d is t in c t
p h e n o t y p e o r ig in a lly
d e s c r ib e d a s c o lla g e n +/
42. T is s u e E n g in e e r in g o f S k in
• C D 3 4 + e x p r e s s io n
d e c r e a s e s w it h t im e
w h ils t e x p r e s s io n o f
p r o lin e -4 - h y d r o x y la s e
in c r e a s e s , a n e n z y m e
r e q u ir e d f o r p r o d u c in g
c o lla g e n
• R e s e a rc h o n s u b - An incisional back wound at day 10 post-wounding in
a C57BL/6 mouse. Sub-lethally irradiated C57BL/6
mice underwent bone marrow reconstitution with bone
le t h a lly ir r a d ia t e d m ic e marrow from C57BL/6 mice
s h o w s th a t th e
r e v e r s io n o f C D 3 4
e x p r e s s io n m a y
43. T is s u e E n g in e e r in g o f S k in
H y p e r t r o p h ic S c a r s
• H y p e r t r o p h ic s c a r s
a r e r e d , t h ic k a n d
r a is e d .
• D o n o t e x te n d b e yo n d
t h e s it e o f in ju r y o r
in c is io n .
• H y p e r t r o p h ic s c a r s
h a v e o r ie n t e d c o lla g e n
• G e t s b e t t e r w it h t im e ,
ho w e ve r c a n be
re d u c e d b y u s e o f
44. T is s u e E n g in e e r in g o f S k in
C o n tra c tu re s
• O c c u r s m a in ly d u e t o
b u r n in ju r ie s
• It is a p e r m a n e n t
t ig h t e n in g o f s k in .
• M a k e s t h e t is s u e s
r e s is t a n t t o s t r e t c h in g
a n d p re v e n ts n o rm a l
m o v e m e n t o f th e
a ffe c te d a re a .
45. T is s u e E n g in e e r in g o f S k in
Tr e a t m e n t f o r S c a r s
In h ib it in g o v e r p r o d u c t io n o f c o lla g e n a n d
r e d u c t io n o f f ib r o s is .
T r e a t m e n t in c l u d e s :
• S u r g ic a l c o r r e c t io n
• C o m p r e s s io n t h e r a p y
• Ir r a d ia t io n
46. T is s u e E n g in e e r in g o f S k in
P la s t ic / c o s m e t ic S u r g e r y
• In t e r e s t e d in t h e c o r r e c t io n
o f f o r m a n d f u n c t io n .
• F a m o u s f o r a e s t h e t ic
s u rg e ry.
• P la s t ic s u r g e r y a ls o
in c lu d e s a v a r ie t y o f f ie ld s :
- c r a n io f a c ia l s u r g e r y
-b u r n s u r g e r y
-m ic r o s u r g e r y
- p e d ia t r ic s u r g e r y
- c o n g e n it a l d e f e c t
c o r r e c t io n s
47. T is s u e E n g in e e r in g o f S k in
• S k in t is s u e ( s k in
g r a f t in g ) is o n e o f t h e
mos t c ommon
p ro c e d u re s .
• L ip o s u c t io n , b r e a s t
a u g m e n t a t io n , e y e lid s
s u r g e r y , f a c e lif t , t u m m y
t u c k , c o lla g e n in je c t io n s ,
c h e m ic a l p e e l , la s e r s k in
r e s u r f a c in g , r h in o p la s t y ,
b u r n s , t r a u m a t ic in ju r ie s
s u c h a s f a c ia l b o n e
48. T is s u e E n g in e e r in g o f S k in
C o m m e r c ia l A s p e c t s
49. T is s u e E n g in e e r in g o f S k in
IN T E G R A ®
• D e s ig n e d t o m a n a g e m a jo r
b u rn s .
• H a s a p o r e v o lu m e f r a c t io n
o f 9 8 % . M . W . o f c r o s s lin k s
a r e in t h e r a n g e o f 1 2 K +5 K
d a lt o n w it h a n a v e r a g e p o r e
d ia m e t e r o f 3 0 -1 2 0 µ m .
• C o m p r is e s o f b o v in e
c o lla g e n a n d s h a r k
c h o n d r o it in s u lp h a t e w it h
50. T is s u e E n g in e e r in g o f S k in
• T h e m a t e r ia l is g r a f t e d o n t o t h e w o u n d
b e d a n d u n d e r t h is m e m b r a n e
v a s c u lo g e n e s is o c c u r s . O n c e t h e
v a s c u l a r iz a t io n i s c o m p le t e s il ic o n
m e m b r a n e b a r r ie r is r e p la c e d w i t h
p a t i e n t s o w n c e l ls .
51. T is s u e E n g in e e r in g o f S k in
IN T E G R A ® P r o c e d u r e in b r ie f
• We e k 1:
- In t e g r a is a p p lie d t o t h e b u r n in ju r y o r s c a r c o n t r a c t u r e
a n d is a s s e s s e d t h e n e v a lu a t e d .
- W o u n d e x c is e d s u r f a c e f lu id s e v a d in g h e lp it t o a t t a c h .
- T h e w o u n d is c le a n e d a n d t h e d a m a g e d t is s u e o r
c o n t r a c t u r e s c a r is c o m p le t e ly e x c is e d
d o w n t o v ia b le t is s u e in p r e p a r a t io n f o r t h e a p p lic a t io n
o f t h e IN T E G R A t e m p la t e .
• W e e k 2 : D e r m a l c e lls s t a r t m ig r a t in g in m a t r ix a n d
c o lla g e n in IN T E G R A is r e p la c e d b y o r g a n ic
c o lla g e n p r o d u c e d b y n e w d e r m a l c e lls
• W e e k 3 : S ilic o n e r e m o v a l a n d a p p ly in g e p id e r m a l
a u to g ra ft.
•
W e e k 4 -8 : S u c c e s s f u l e n g r a f t m e n t o f s k in
52. T is s u e E n g in e e r in g o f S k in
P r o b le m s w it h IN T E G R A ®
• B o v in e c o lla g e n m a y b r in g f o r t h th e
a n t ig e n ic r e s p o n s e .
• T h e y f a il t o a d h e r e s e c u r e ly .
• T h r e e w e e k s a r e r e q u ir e d t o e x p a n d t h e
d e rm a l a u to g ra ft.
53. T is s u e E n g in e e r in g o f S k in
D e rm a g ra ft®
• A h o p e f o r f a s t e r r e c o v e r y f o r D ia b e t i c
f o o t u l c e r s (D F U )
• D e r m a g r a f t ® is a c r y o p r e s e r v e d h u m a n
f i b r o b la s t - d e r iv e d d e r m a l s u b s t it u t e ; it is
c o m p o s e d o f f ib r o b la s t s d e r iv e d f r o m
n e w b o r n f o r e s k in t is s u e , e x t r a c e llu la r
m a t r i x , a n d a b io a b s o r b a b le s c a f f o ld .
• N e o n a t a l f ib r o b l a s t s r a p i d ly p r o lif e r a t e t o
p r o d u c e c o lla g e n , G A G s a n d g r o w t h
54. T is s u e E n g in e e r in g o f S k in
A D VA N TAG E S
• U s e d in t r e a t m e n t o f
D F U w h ic h if le f t
u n t r e a t e d m a y le a d
a m p u t a t io n o f f o o t .
• D e r m a g r a f t in c r e a s e s
b lo o d f lo w t o D F U w h ic h
r e s u lt s in f a s t e r h e a lin g
• O n ly d is a d v a n t a g e is
s u b m e m b r a n e f lu id
a c c u m u la t io n is m o r e in
D e rm a g ra ft.
55. T is s u e E n g in e e r in g o f S k in
IC X - S K N b y IN T E R C Y T E X
• A im e d t o p r o v id e b e t t e r
h e a lin g f o r b u r n s a n d a c u t e
w o u n d s v ic t im s .
• C o m p r is e s o f a llo g e n e ic
h u m a n d e r m a l f ib r o b la s t s s e t
in a n a t u r a l h u m a n c o lla g e n
m a t r ix , w h ic h m im ic s t h e
s t r u c t u r e o f s k in a n d is
in t e n d e d a s a s k in g r a f t
r e p la c e m e n t . A n a d d it io n a l
la y e r o f h u m a n k e r a t in o c y t e s
m a y b e in c lu d e d t o f o r m a n
e p id e r m a l la y e r .
56. T is s u e E n g in e e r in g o f S k in
• O t h e r S k i n g r a f t s u b s t it u t e s a v a i la b l e in
t h e m a r k e t a r e T r a n s c y t e ® , A p lig r a f t ® ,
O r c e l® , B io b r a n e .
• C e ll d e liv e r y a p p r o a c h e s a r e t h e n e x t
u p c o m in g f ie l d in T is s u e
E n g in e e r in g o f S k in .
• K e r a t in o c y t e s c a n b e g r o w n in t o
in t e g r a t e d c e ll s h e e t s , m a d e in t o
s u s p e n s io n s a n d s p r a y e d o n t o w o u n d
s i t e s w it h o r w it h o u t f ib r in s . E g . :
57. T is s u e E n g in e e r in g o f S k in
• M y s k in ® is a n o t h e r p r o d u c t w h ic h is
b a s e d o n s a m e p r in c ip le e x c e p t
c h e m ic a lly d e f in e d p o ly m e r c a r r ie r
d r e s s in g .
• E p id e x ® u s e s c e lls c u l t u r e d f r o m h a i r
f o llic le s a n d d e liv e r e d a s s m a ll s h e e t s
58. T is s u e E n g in e e r in g o f S k in
C h a lle n g e s
59. T is s u e E n g in e e r in g o f S k in
• U s in g t h e r ig h t k in d o f s e r u m : T h e w id e l y
us e d c u lt u r e m e t h o d o lo g y u s e s m u r in e
f i b r o b la s t s a n d b o v in e s e r u m . M u r in e
c e ll s m i g h t c o n t a in v i r u s e s a b le t o
t r a n s f o r m h u m a n c e lls . B o v in e s e r u m m a y
b e in f e c t e d b y B S E .
• B io c o m p a t i b ilit y , m e c h a n ic a l & h a n d lin g
p r o p e r t ie s .
• H a s m a n y c lin ic a l b e n e f it s b u t ma ny
e x p e c t a t i o n s b o t h c li n ic a l a s w e ll a s
60. T is s u e E n g in e e r in g o f S k in
• T r e a t in g d e e p e r w o u n d s .
• B e t t e r a d h e r in g o f k e r a t in o c y t e s t o t h e
d e r m is s i t e .
• C o s t o f a u t o m a t i o n t o o h ig h f o r t h e
c o m p a n ie s t o s u r v iv e .
• L o t s o f r e g u la t io n la id b y F D A .
61. T is s u e E n g in e e r in g o f S k in
Fu tu re
62. T is s u e E n g in e e r in g o f S k in
• H u m a n e m b r y o n ic s t e m c e ll s ( h E S C s ) a r e
a p r o m is i n g s o u r c e o f s k in c e lls f o r
e n g in e e r e d s k in e q u iv a le n t s a s t h e y h a v e
a p o t e n t ia l t o b e a s a f e s o u r c e o f
u n lim it e d a m o u n t o f s k in c e ll s .
• B e t t e r a d h e s io n o f k e r a t in o c y t e s u s in g
g e n e th e ra p y.
63. T is s u e E n g in e e r in g o f S k in
• N a n o f i b e r s , w h ic h m i m ic c o lla g e n f ib r il s i n
t h e e x t r a c e l lu la r m a t r ix ( E C M ), c a n b e
c re a te d fro m a h o s t o f n a tu ra l a n d
s y n t h e t i c c o m p o u n d s a n d h a v e m u lt ip l e
p r o p e r t ie s t h a t m a y b e b e n e f ic ia l t o b u r n
w o u n d c a re .
• C o s t e f f ic i e n t .
• L e s s s t r i n g e n t r e g u la t i o n s .
64. T is s u e E n g in e e r in g o f S k in
C o n c lu s io n
65. T is s u e E n g in e e r in g o f S k in
• M a n y im p o r t a n t c lin ic a l m ile s t o n e s h a v e b e e n
r e a c h e d a n d t h e n u m b e r o f a r t if ic ia l s k in
s u b s t it u t e s lic e n s e d f o r c lin ic a l u s e is g r o w in g ,
b u t t h e y h a v e y e t t o r e p la c e t h e c u r r e n t
‘ ‘ g o ld s t a n d a r d ’ ’ o f a n a u t o lo g o u s s k in
g ra ft.
• C u r r e n t ly a v a ila b le s k in s u b s t it u t e s o f t e n
s u f f e r f r o m a r a n g e o f p r o b le m s t h a t in c lu d e
p o o r in t e g r a t io n w h ic h in m a n y c a s e s is a
d ir e c t r e s u lt o f in a d e q u a t e v a s c u la r is a t io n ,
s c a r r in g a t t h e g r a f t m a r g in s a n d a c o m p le t e
la c k o f d if f e r e n t ia t e d s t r u c t u r e s .
• T h e u lt im a t e g o a l f o r s k in t is s u e e n g in e e r s is t o
r e g e n e r a t e s k in s u c h t h a t t h e c o m p le t e
s t r u c t u r a l a n d f u n c t io n a l p r o p e r t ie s o f t h e
w o u n d e d a re a a re
r e s t o r e d t o t h e le v e ls b e f o r e in ju r y .
66. T is s u e E n g in e e r in g o f S k in
Re fe re n c e s
67. T is s u e E n g in e e r in g o f S k in
• h t t p :/ / it h a c a . r ic e . e d u / k z / U S A T o d a y / S k in A r t ic le .
h tm
• h t t p :/ / w w w . c b t e . g r o u p . s h e f . a c . u k / r e s e a r c h / t e
2 .h t m l
• h t t p :/ / o u r o b o r o s . w o r d p r e s s . c o m / 2 0 0 7 / 0 2 / 2 1 / t i
s s u e - e n g in e e r in g - t h e - s k in /
• h t t p :/ / f in d a r t ic le s . c o m / p / a r t ic le s / m i _ q a 3 9 7 7 / is _
2 0 0 0 0 5 / a i _ n 8 9 0 2 6 6 9 / p g _ 2 ? t a g = a r t B o d y ;c o l 1
• h t t p :/ / e n . w ik ip e d ia . o r g / w ik i / T is s u e _ e n g in e e r in g
• P r o g r e s s a n d o p p o r t u n it ie s f o r t is s u e -
e n g in e e r e d s k in , S . M a c N e il , Nature , 4 4 5 ,
8 7 4 -8 8 0 (2 0 0 7 )
• T is s u e e n g in e e r in g o f r e p la c e m e n t s k in : t h e
c r o s s r o a d s o f b io m a t e r ia ls , w o u n d h e a lin g ,
68. T is s u e E n g in e e r in g o f S k in
• E m e r g in g T r e a t m e n t s in D ia b e t ic W o u n d C a r e
b y T h a n h D in h , D P M ;1 H a u P h a m , D P M ;1 A r is t id is
V e v e s , M D 2 - V O L U M E : 1 4 P U B L IC A T IO N D A T E :
F e b 1 0 2 0 0 2 Is s u e 1
• S k in s u b s t it u t e s f r o m c u lt u r e d c e lls a n d
c o lla g e n - G A G p o ly m e r s - S . T . B o y c e
• h t t p :// w w w . in t e r c y t e x . c o m / ic x / p r o d u c t s / w o u n d
c a r e / ic x s k n /
• h t t p :// w w w . b u r n c a r e r e h a b . c o m / p t / r e / jb u r n c r / a
b s t r a c t . 0 1 2 5 3 0 9 2 -2 0 0 8 0 9 0
• h t t p :// w w w . b u r n s u r v iv o r . c o m / s u r g ic a l _ p r o c e d u
r e _ s k in g r a f t s . h t m l
• P ic t u r e s o u r c e : h t t p :// w w w . im a g e s . g o o g le . c o m
• V id e o s o u r c e :
69. T is s u e E n g in e e r in g o f S k in
• In vitro s k in ir r it a t io n : f a c t s a n d f u t u r e . S t a t e
o f t h e a r t r e v ie w o f m e c h a n is m s a n d m o d e ls .
Toxicol. In Vitro 1 8 , 2 3 1 – 2 4 3 (2 0 0 4 ). b y W e ls s , T .,
B a s k e tte r, D . A. & S c h ro d e r, K. R.
• T is s u e E n g in e e r in g : P a ls s o n , B e r n h a r d &
B h a t ia , S a n g e e t a ; P e a r s o n P r e n t ic e H a ll
B io e n g in e e r in g .
• M e t h o d s o f T is s u e E n g in e e r in g : A t a la , A n t h o n y
& L a n z a R o b e r t ; A c a d e m ic P r e s s .
70. T is s u e E n g in e e r in g o f S k in
Q u e s t io n s ?
71. T is s u e E n g in e e r in g o f S k in
Th a n k Yo u !