[ACS Symposium Series] Polymeric Materials and Artificial Organs Volume 256 || Silicones in Artificial Organs

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  • 6 Silicones in Artificial Organs

    . E. FRISCH

    Dow Corning Corporation, Midland, MI 48640

    Starting with the si l icone elastomer hydrocephalus shunt in 1955, si l icone elastomer has become widely used as a soft, f l ex ib le , elastomeric material of construction for artificial organs and implants for the human body. When prepared with controls to assure its duplication and freedom from contamination, specific formulations have excellent biocompatibility, biodurabil i ty, and a long history of c l i n i c a l safety. Properties can be varied to meet the needs in many different implant applications. Silicone elastomer can be fabricated in a wide variety of forms and shapes by most all of the techniques used to fabricate thermosetting elastomers. Radiopacity can be increased by fillers such as barium sulfate or powdered metals. It can be s te r i l i zed by ethylene oxide, steam autoclave, dry heat, or radiation. Shel f - l i fe at ambient conditions is indefinite. When implanted the host reaction is typical ly limited to encapsulation of the implant in fibrous tissue. Silicone elastomer implants have become used in essentially a l l surgical specialties including neurosurgery, ophthalmology, plast ic surgery, urology, orthopaedic surgery, obstetrics and gynecology, otolaryngology, cardiovascular surgery, and others. Significant advances have been made in si l icone elastomer technology in recent years. A medical grade high performance si l icone elastomer with excellent resistance to tear propagation and fatigue flexing has been developed and qualified for use in the implants used in bone and joint reconstruction. Properties, biocompatibility, biodurability and medical applications for si l icone elastomers w i l l be discussed.

    0097-6156/84/0256-0063S09.75/0 1984 American Chemical Society

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    In Polymeric Materials and Artificial Organs; Gebelein, C.; ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

  • 64 POLYMERIC MATERIALS AND ARTIFICIAL ORGANS

    S i l i c o n e i s t h e common name f o r p o l y d i o r g a n o s i l o x a n e s . T h e t e r m a l l e g e d l y o r i g i n a t e d b e c a u s e i t w a s t h o u g h t s i l i c o n - c o n t a i n i n g m a t e r i a l s f i r s t p r e p a r e d b y K i p p i n g O J a t a b o u t t h e t u r n o f t h e c e n t u r y m i g h t b e s i l i c o n - c o n t a i n i n g a n a l o g u e s o f k e t o n e s .

    C ( C H 3 ) 2 = 0 - [ S i ( C H 3 ) 2 0 - ] x

    A c e t o n e P o l y d i m e t h y l s i l o x a n e

    M o d e r n p r o c e s s e s f o r s y n t h e s e s o f s i l i c o n e s w e r e d e v e l o p e d f r o m r e s e a r c h c o n d u c t e d i n t h e 1 9 3 0 ' s . S i l i c o n e s w e r e f i r s t m a n u f a c t u r e d i n q u a n t i t y d u r i n g W o r l d W a r I I f o r t h e U . S . g o v e r n m e n t t o i m p r o v e t h e p e r f o r m a n c e o f U . S . a i r c r a f t . A f t e r W o r l d W a r I I a n d p r i o r t o d i s t r i b u t i o n f o r o t h e r t h a n a i r c r a f t u s e , a n i m a l s t u d i e s w e r e u n d e r t a k e n t o e v a l u a t e b i o l o g i c a l c h a r a c t e r i s t i c s . T h e f i n d i n g s i n d i c a t e d t h a t n o n - v o l a t i l e m e t h y l -a n d m i x e d m e t h y l - p h e n y l p o l y s i l o x a n e s a s a c l a s s w e r e v e r y l o w i n t o x i c i t y . A l s o , f i n i s h e d s i l i c o n e r e s i n s w e r e p h y s i o l o g i c a l l y i n e r t a n d p r e s e n t e d n o h e a l t h h a z a r d s . P u b l i c a t i o n ( 2 - 3 ) o f t h e s t u d y s t i m u l a t e d i n t e r e s t i n u s i n g s i l i c o n e s f o r a r t i f i c i a l o r g a n s b e c a u s e o f t h e n e e d f o r i m p l a n t a b l e , b i o c o m p a t i b l e , s o f t , f l e x i b l e , e l a s t o m e r i c m a t e r i a l s . T h i s p a p e r w i l l r e v i e w t h e c h e m i s t r y , t h e p h y s i c a l a n d b i o l o g i c a l c h a r a c t e r i s t i c s , a n d a p p l i c a t i o n s o f s i l i c o n e s i n a r t i f i c i a l o r g a n s .

    C H E M I S T R Y

    T h e s y n t h e s i s o f s i l i c o n e s t a r t s w i t h n a t u r a l l y o c c u r r i n g s i l i c o n d i o x i d e ( q u a r t z , s a n d , o r q u a r t z i t e r o c k ) . S i l i c o n d i o x i d e i s r e a c t e d w i t h c a r b o n a t h i g h t e m p e r a t u r e t o y i e l d e l e m e n t a l s i l i c o n .

    S i 0 2 + C S i + C 0 2

    T h e h a r d , c r y s t a l l i n e , b r i t t l e e l e m e n t a l s i l i c o n i s p u l v e r i z e d a n d r e a c t e d d i r e c t l y w i t h m e t h y l c h l o r i d e a t e l e v a t e d t e m p e r a t u r e .

    S i + C H 3 C 1 _ ^ S i C l 4 + C H 3 S i C l 3 + ( C H 3 ) 2 S i C l 2

    + ( C H 3 ) 3 S i C l + ( C H 3 ) 4 S i

    A m i x t u r e o f m e t h y l - a n d c h l o r i n e - c o n t a i n i n g s i l a n e s r a n g i n g f r o m t e t r a c h l o r o s i l a n e t o t e t r a m e t h y l s i l a n e i s o b t a i n e d . C o n d i t i o n s a r e g e n e r a l l y a d j u s t e d t o p r o d u c e a m a x i m u m a m o u n t o f d i m e t h y l d i c h l o r o s i l a n e , t h e m o n o m e r f o r p o l y d i m e t h y l s i l o x a n e s . T h e l i q u i f i e d s i l a n e s a r e s e p a r a t e d b y f r a c t i o n a l d i s t i l l a t i o n .

    P o l y d i m e t h y l s i l o x a n e i s p r e p a r e d b y c o n d e n s a t i o n c o p o l y m e r -i z a t i o n o f d i m e t h y l d i c h l o r o s i l a n e w i t h w a t e r .

    ( C H 3 ) 2 S i C l 2 + H 2 0 - [ S i ( C H 3 ) 2 0 - ] x + 2 x HC1

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    In Polymeric Materials and Artificial Organs; Gebelein, C.; ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

  • 6. FRISCH Silicones in Artificial Organs 65

    T h e p r e p o l y m e r t h u s o b t a i n e d i s f u r t h e r p o l y m e r i z e d t o y i e l d s p e c i f i c s i l i c o n e p o l y m e r s w h i c h c a n v a r y i n m o l e c u l a r w e i g h t ( a v e r a g e a n d d i s t r i b u t i o n ) , p r e s e n c e o r a b s e n c e a n d c o n t e n t o f f i l l e r s o r o t h e r a d d i t i v e s , t y p e o f o r g a n i c l i g a n d s a t t a c h e d t o s i l i c o n , t h e p o s s i b l e p r e s e n c e o f r e a c t i v e r a d i c a l s s u c h a s v i n y l l i g a n d s o n s i l i c o n f o r u s e i n c r o s s - l i n k i n g , a n d i n o t h e r w a y s . A b o u t 6 0 , 0 0 0 s i l i c o n - c o n t a i n i n g c o m p o u n d s a r e k n o w n . H o w e v e r , o n l y a f e w h a v e b e e n f o u n d t o b e u s e f u l a n d h a v e t h u s b e c o m e c o m m e r c i a l l y a v a i l a b l e . S i l i c o n e s u s e d i n a r t i f i c i a l o r g a n s a n d i m p l a n t s h a v e p r i m a r i l y b e e n t h e p o l y d i m e t h y l s i l o x a n e s .

    H y d r o c e p h a l u s S h u n t

    H o l t e r ' s s u c c e s s f u l d e v e l o p m e n t o f a s i l i c o n e e l a s t o m e r h y d r o -c e p h a l u s s h u n t ( 4 ) ( F i g u r e s 1 - 2 ) i n 1 9 5 5 h e r a l d e d t h e e r a o f i m p l a n t s . No e f f e c t i v e t r e a t m e n t f o r h y d r o c e p h a l u s w a s k n o w n a t t h e t i m e . T h u s , b y 1 9 5 7 , o n l y t w o y e a r s a f t e r t h e s h u n t w a s f i r s t u s e d , a n d c o n t i n u i n g t o d a y , e s s e n t i a l l y e v e r y h y d r o c e p h a l i c c h i l d b o r n i n t h e d e v e l o p e d c o u n t r i e s o f t h e w o r l d h a s r e c e i v e d a s i l i c o n e e l a s t o m e r h y d r o c e p h a l u s s h u n t i m p l a n t . H y d r o c e p h a l u s o c c u r s i n a p p r o x i m a t e l y o n e o u t o f e v e r y 4 0 0 t o 6 0 0 c h i l d r e n b o r n a l i v e . T h e h y d r o c e p h a l u s s h u n t i s o n e o f t h e o l d e s t , a n d a l s o o n e o f t h e m o s t w i d e l y u s e d o f a l l s i l i c o n e e l a s t o m e r i m p l a n t s . Some i n d i v i d u a l s h a v e now h a d s h u n t i m p l a n t s f o r m o r e t h a n 2 5 y e a r s . T h e e x c e l l e n t b i o c o m p a t i b i l i t y o f i m p l a n t g r a d e s o f s i l i c o n e e l a s t o m e r i s e v i d e n c e d b y t h e e s s e n t i a l a b s e n c e o f a d v e r s e b i o l o g i c a l r e s p o n s e i n t h i s l o n g t e r m , l a r g e v o l u m e u s e .

    M e d i c a l G r a d e S i l i c o n e E l a s t o m e r s

    M e d i c a l g r a d e s i l i c o n e e l a s t o m e r s b e c a m e a v a i l a b l e i n t h e e a r l y 1 9 6 0 ' s . " M e d i c a l g r a d e " r e f e r s t o s i l i c o n e e l a s t o m e r s s p e c i f i -c a l l y f o r m u l a t e d , m a n u f a c t u r e d a n d q u a l i f i e d f o r i m p l a n t u s e s . T h e f o r m u l a t i o n s c o n t a i n n o m a t e r i a l s w i t h p o t e n t i a l f o r b i o d g r a -d a t i o n o r a d v e r s e b i o c o m p a t i b i l i t y . M a n u f a c t u r i n g a n d p r o c e s s i n g a r e d o n e u n d e r c a r e f u l l y c o n t r o l l e d , c l e a n c o n d i t i o n s t o a s s u r e b a t c h - t o - b a t c h d u p l i c a t i o n , a n d f r e e d o m f r o m a d u l t e r a t i o n , c o n t a m i n a t i o n , a n d c r o s s c o n t a m i n a t i o n . B a t c h - t o - b a t c h t e s t s i n c l u d e a s s e s s m e n t o f c h e m i c a l , p h y s i c a l , a n d b i o l o g i c a l p r o p e r -t i e s . T h e m a t e r i a l s m u s t e l i c i t n o c y t o t o x i c r e a c t i o n b y d i r e c t c o n t a c t t i s s u e - c e l l c u l t u r e t e s t i n g ( 5 , 6 ) . Q u a l i f i c a t i o n o f a c o n t r o l l e d f o r m u l a t i o n f o r i m p l a n t u s e t y p i c a l l y r e q u i r e s 2 - y e a r m i n i m u m b i o c o m p a t i b i l i t y ( h o s t a n d t i s s u e r e a c t i o n ) {7) a n d 2 - y e a r b i o d u r a b i l i t y ( i m p l a n t r e a c t i o n ) s t u d i e s .

    H i g h - c o n s i s t e n c y t h e r m o s e t t i n g m e d i c a l g r a d e s i l i c o n e e l a s -t o m e r c o m p o u n d s a r e p r e p a r e d f r o m h i g h m o l e c u l a r w e i g h t p o l y d i o r -g a n o s i l o x a n e s c o m p o u n d e d w i t h h i g h - s u r f a c e f u m e d s i l i c a ( a p p r o x -i m a t e l y 4 0 0 m / g ) . S i l i c a i s t h e o n l y m a t e r i a l k n o w n t h a t a d e q u a t e l y r e i n f o r c e s s i l i c o n e e l a s t o m e r .

    V u l c a n i z a t i o n r e q u i r e s c r o s s - l i n k i n g p o l y m e r c h a i n s . I n o n e

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    In Polymeric Materials and Artificial Organs; Gebelein, C.; ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

  • POLYMERIC MATERIALS AND ARTIFICIAL ORGANS

    F i g u r e 1 . A s i l i c o n e e l a s t o m e r h y d r o c e p h a l u s s h u n t . T h i s t y p e o f s h u n t i s u s e d t o d r a i n c e r e b r o s p i n a l f l u i d f r o m t h e v e n t r i c l e o f t h e b r a i n t o e i t h e r t h e v a s c u l a r s y s t e m o r t o t h e p e r i t o n e a l c a v i t y . T h e f i r s t h y d r o c e p h a l u s s h u n t w a s d e v e l o p e d b y H o l t e r i n 1 9 5 5 . T h e s h u n t i n t h i s i l l u s t r a t i o n c o n t a i n s a d u a l f l u s h i n g c h a m b e r t o a s s u r e c o n t i n u a l f u n c t i o n o f t h e s h u n t , a n d i s d e s i g n e d t o d r a i n c e r e b r a l s p i n a l f l u i d f r o m t h e v e n t r i c l e o f t h e b r a i n t o t h e p e r i t o n e a l c a v i t y .

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    In Polymeric Materials and Artificial Organs; Gebelein, C.; ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

  • FRISCH Silicones in Artificial Organs

    F i g u r e 2. P o s i t i o n i n g o f t h e h y d r o c e p h a l u s s h u n t i n a c h i l d ' s b o d y . T h e e n t i r e s h u n t i s i m p l a n t e d s u b d e r m a l l y . T h e t i p o f t h e s h u n t i s i n s e r t e d i n t o t h e v e n t r i c l e o f t h e b r a i n t h r o u g h a h o l e m a d e i n t h e s k u l l , w h i l e t h e d r a i n a g e c a t h e t e r i s p l a c e d i n t h e p e r i t o n e a l c a v i t y t h r o u g h a s m a l l i n c i s i o n i n t h e p e r i t o n e a l l i n i n g . A n e x t r a l e n g t h o f t h e p e r i t o n e a l c a t h e t e r i s g e n e r a l l y l e f t s o t h a t t h e c h i l d may g r o w w i t h o u t d i s l o d g i n g t h e c a t h e t e r f r o m t h e p e r i t o n e a l c a v i t y .

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    In Polymeric Materials and Artificial Organs; Gebelein, C.; ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

  • 68 POLYMERIC MATERIALS AND ARTIFICIAL ORGANS

    type o f c r o s s - l i n k i n g , s i l i c o n - h y d r o g e n l i g a n d s , contained as small amounts o f methylhydrogensiloxy copolymer i n one formula-t i o n , r e a c t with s i l i c o n - v i n y l l i g a n d s , contained as m e t h y l v i n y l -s i l o x y copolymer i n small amounts i n a second f o r m u l a t i o n . When the two formulations are i n t i m a t e l y blended and heated i n the presence o f a c a t a l y s t , c r o s s - l i n k i n g occurs. T y p i c a l c a t a l y s t s i n c l u d e t r a c e q u a n t i t i e s o f rar e metals, such as platinum. The c r o s s - l i n k s are dimethylene r a d i c a l s c o v a l e n t l y bonded between s i l i c o n atoms i n separate polymer chains.

    C r o s s - l i n k i n g e s s e n t i a l l y forms a che m i c a l l y bonded network matrix o f one g i a n t molecule. Organic peroxides are a l s o used as v u l c a n i z a t i o n c a t a l y s t s .

    B i o c o m p a t i b i l i t y o f Medical Grade S i l i c o n e Elastomers When once formulated o r processed s i l i c o n e elastomer cannot be adequately c h a r a c t e r i z e d by sh o r t term s t u d i e s to guarantee t h a t h i s t o r i c animal and c l i n i c a l data are r e l e v a n t to assure reason-able s a f e t y f o r implant use. Unlike some substances where a n a l y s i s and acute e v a l u a t i o n s can provide thorough c h a r a c t e r i z a -t i o n chemical, p h y s i c a l , and acute b...

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