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Tissue Engineering of Skin

Tissue Engineering of Skin

Published in: Education, Technology
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  • 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
  • 7. T is s u e E n g in e e r in g o f 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 !

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