Silicones in Artificial Organs - ACS Symposium Series (ACS

6 Silicones in Artificial Organs Ε. E. FRISCH

Downloaded by UNIV OF IOWA on November 13, 2014 | http://pubs.acs.org Publication Date: June 8, 1984 | doi: 10.1021/bk-1984-0256.ch006

Dow Corning Corporation, Midland, MI 48640

Starting with the silicone elastomer hydroceph alus shunt in 1955, silicone elastomer has become widely used as a soft, f l e x i b l e , 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, b i o d u r a b i l i t y , 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 applica tions. Silicone elastomer can be fabricated in a wide variety of forms and shapes by most all of the techniques used to fabricate thermosetting elasto mers. Radiopacity can be increased by fillers such as barium sulfate or powdered metals. It can be s t e r i l i z e d by ethylene oxide, steam autoclave, dry heat, or radiation. S h e l f - l i f e at ambient condi tions i s indefinite. When implanted the host reaction i s t y p i c a l l y 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, plastic surgery, urology, orthopae dic surgery, obstetrics and gynecology, otolaryn gology, cardiovascular surgery, and others. Significant advances have been made in silicone elastomer technology in recent years. A medical grade high performance s i l i c o n e elastomer with excellent resistance to tear propagation and fatigue flexing has been developed and qualified for use in the implants used in bone and j o i n t reconstruction. Properties, biocompatibility, biodurability and medical applications for silicone elastomers w i l l be discussed. 0097-6156/84/0256-0063S09.75/0 © 1984 American Chemical Society

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

64

POLYMERIC MATERIALS A N D 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 . The 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 was 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 by K i p p i n g O J a t about t h e t u r n o f t h e c e n t u r y might be 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(CH3)2=0

-


Acetone

[Si(CH3)20-]

x

Polydimethylsiloxane

Modern 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 were developed from research conducted i n the 1930's. S i l i c o n e s were first manufactured in quantity during World War 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 . After W o r l d War 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 aircraft use, animal studies were undertaken to evaluate biological c h a r a c t e r i s t i c s . The 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 methyl and mixed 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 as a c l a s s were v e r y l o w i n toxicity. Also, f i n i s h e d s i l i c o n e r e s i n s were physiologically i n e r t a n d p r e s e n t e d no h e a l t h h a z a r d s . Publication (2-3) of the study stimulated interest in using silicones for artificial organs because o f t h e need 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 , soft, flexible, elastomeric materials. This paper will review the chemistry, the physical and b i o l o g i c a l characteristics, and applications of silicones in a r t i f i c i a l organs. CHEMISTRY The 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 dioxide (quartz, sand, or quartzite rock). Silicon dioxide is reacted with carbon at high temperature to y i e l d elemental silicon. Si0

2

+ C

£

• Si + C02

The 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 ized and r e a c t e d directly with methyl chloride at elevated temperature. Si +

+ CH3C1 _ ^ S i C l (CH3)3SiCl

+

4

+ CH3SiCl3

+

(CH3)2SiCl

2

(CH3)4Si

A mixture o f m e t h y l - and 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 ranging from t e t r a c h l o r o s i l a n e to 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 . Condi tions are generally adjusted to produce a maximum amount of dimethyldichlorosilane, t h e monomer f o r polydimethylsiloxanes. The 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 by f r a c t i o n a l d i s t i l l a t i o n . Polydimethylsiloxane i s prepared by c o n d e n s a t i o n copolymerization of dimethyldichlorosilane with water. χ

(CH3)2SiCl

2

+ χ

H20

-[Si(CH3)20-]

x

+ 2x


HC1

6.

FRISCH

65

Silicones in Artificial Organs

The 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 specific s i l i c o n e polymers which can vary in molecular weight (average and d i s t r i b u t i o n ) , p r e s e n c e o r absence and c o n t e n t of f i l l e r s or other a d d i t i v e s , type of organic l i g a n d s attached to s i l i c o n , the p o s s i b l e presence of r e a c t i v e r a d i c a l s such as v i n y l l i g a n d s on 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 ways. 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 compounds a r e known. However, o n l y a few have been f o u n d t o be u s e f u l and have t h u s become commercially available. S i l i c o n e s used i n a r t i f i c i a l o r g a n s and i m p l a n t s have p r i m a r i l y been the p o l y d i m e t h y l s i l o x a n e s .


Hydrocephalus

Shunt

Holter's s u c c e s s f u l development of a s i l i c o n e elastomer hydrocephalus shunt (4) (Figures 1-2) i n 1955 heralded the era of implants. 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 the time. Thus, by 1 9 5 7 , o n l y two y e a r s a f t e r the shunt was f i r s t u s e d , and 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 born 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 has r e c e i v e d a silicone elastomer hydrocephalus shunt implant. Hydrocephalus o c c u r s i n a p p r o x i m a t e l y one o u t o f e v e r y 400 t o 600 c h i l d r e n b o r n alive. The h y d r o c e p h a l u s s h u n t i s one o f t h e o l d e s t , and a l s o one o f t h e most w i d e l y used o f a l l s i l i c o n e e l a s t o m e r implants. 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 more t h a n 25 years. The excellent biocompatibility of implant grades of silicone elastomer is evidenced by the essential absence of adverse b i o l o g i c a l response i n t h i s long t e r m , l a r g e volume u s e . Medical

Grade

Silicone

Elastomers

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 became a v a i l a b l e i n t h e early 1960's. "Medical grade" r e f e r s to s i l i c o n e elastomers specifically formulated, manufactured and q u a l i f i e d f o r implant uses. The f o r m u l a t i o n s c o n t a i n no 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 é 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 and p r o c e s s i n g a r e done under 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 batch-to-batch duplication, and freedom from adulteration, contamination, and cross contamination. Batch-to-batch tests 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 , and b i o l o g i c a l p r o p e r ties. The m a t e r i a l s m u s t e l i c i t no c y t o t o x i c r e a c t i o n by d i r e c t contact tissue-cell culture testing (5,6). Q u a l i f i c a t i o n of 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 implant use t y p i c a l l y r e q u i r e s 2-year minimum biocompatibility (host and tissue reaction) {7) and 2-year biodurability (implant reaction) studies. H i g h - c o n s i s t e n c y thermosetting medical grade s i l i c o n e e l a s tomer compounds 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 polydiorganosiloxanes compounded w i t h h i g h - s u r f a c e fumed s i l i c a (approximately 400 m /g). Silica is the only material known that adequately reinforces s i l i c o n e elastomer. V u l c a n i z a t i o n requires c r o s s - l i n k i n g polymer c h a i n s . In one




F i g u r e 1. A s i l i c o n e elastomer hydrocephalus shunt. This type of shunt i s used to d r a i n c e r e b r o s p i n a l f l u i d from the v e n t r i c l e of the b r a i n to e i t h e r the v a s c u l a r system or to the p e r i t o n e a l c a v i t y . The f i r s t hydrocephalus s h u n t was d e v e l o p e d by H o l t e r i n 1 9 5 5 . The 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 dual f l u s h i n g chamber to 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 , and i s d e s i g n e d to d r a i n cerebral s p i n a l f l u i d from the v e n t r i c l e of the b r a i n to the p e r i t o n e a l cavity.



FRISCH


F i g u r e 2. P o s i t i o n i n g of the hydrocephalus shunt i n a c h i l d ' s body. The 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 . The 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 made 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 catheter i s placed in the peritoneal c a v i t y through a small i n c i s i o n in the p e r i t o n e a l l i n i n g . An e x t r a length of the 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 so t h a t the 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 peritoneal cavity.


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 , c o n t a i n e d as small amounts o f methylhydrogensiloxy copolymer i n one formulat 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 , c o n t a i n e d 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 f o r m u l a t i o n s a r e i n t i m a t e l y blended and heated i n t h e presence o f a c a t a l y s t , c r o s s - l i n k i n g o c c u r s . 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 r a r e metals, such as platinum. The c r o s s - l i n k s a r e 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 c h a i n s . 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 c h e m i c a l l y bonded network matrix o f one g i a n t molecule. Organic peroxides a r e a l s o used as vulcanization catalysts. 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 s h o r t term s t u d i e s t o guarantee t h a t h i s t o r i c animal and c l i n i c a l data a r e r e l e v a n t t o assure reasona b l e s a f e t y f o r implant use. U n l i k e 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 p r o v i d e thorough c h a r a c t e r i z a t i o n c h e m i c a l , p h y s i c a l , and acute b i o c o m p a t i b i l i t y t e s t s , used alone o r i n combination, a r e n o t adequate. Formulation e r r o r s or contamination, which c o u l d a d v e r s e l y a f f e c t c h r o n i c biocompati b i l i t y c h a r a c t e r i s t i c s , may i n a d v e r t e n t l y o c c u r and n o t be d e t e c t e d by short-term t e s t i n g . When used i n implants reasonable assurance o f d u p l i c a t i o n must i n c l u d e c h a r a c t e r i z a t i o n o f a l l b a s i c i n g r e d i e n t s , c o n t r o l o f t h e manufacturing p r o c e s s e s , and s t r i n g e n t q u a l i t y assurance. A l l f o r m u l a t i o n , compounding, and p r o c e s s i n g o f elastomers must be done i n f a c i l i t i e s which comply with Good Manufacturing P r a c t i c e Regulations as a minimum. S i l i c o n e elastomer prepared under l e s s s t r i n g e n t c o n d i t i o n s , such as those t y p i c a l l y used t o produce elastomer f o r i n d u s t r i a l use cannot be adequately upgraded by a f t e r - t h e - f a c t s h o r t - t e r m t e s t i n g t o assure t h a t c h r o n i c b i o c o m p a t i b i l i t y c h a r a c t e r i s t i c s have been d u p l i c a t e d . The c h r o n i c b i o c o m p a t i b i l i t y and b i o d u r a b i l i t y o f medical grade s i l i c o n e elastomers have been e v a l u a t e d . In one study specimens o f medical grade s i l i c o n e elastomer were implanted i n purebred beagle dogs f o r 3 y e a r s . T i s s u e r e a c t i o n s t y p i c a l l y i n c l u d e d an i n i t i a l inflammatory r e a c t i o n a s s o c i a t e d with t h e i n t r o d u c t i o n o f a f o r e i g n m a t e r i a l . The r e a c t i o n appeared t o be s e l f - l i m i t i n g and f u r t h e r d i m i n i s h e d with time, l e a v i n g a d e f i n a b l e f i b r o u s c a p s u l e around t h e implant as t h e t e r m i n a l observat i o n . The most n o t i c e a b l e f i b r o u s - t i s s u e responses were caused by t h e i n t r a m u s c u l a r i m p l a n t s , w i t h l e s s i n t e n s e r e a c t i o n s r e s p e c t i v e l y i n subcutaneous and i n t r a p e r i t o n e a l s i t e s . The r e s u l t s o f t e s t i n g done on c l i n i c a l l a b o r a t o r y specimens c o l l e c t ed d u r i n g t h e t e r m i n a l weeks o f t h e 3-year i m p l a n t a t i o n study f o r e v a l u a t i o n o f c l i n i c a l chemistry i n d i c a t e d t h a t a l l values were w i t h i n normal l i m i t s f o r t h e s p e c i e s , with no a b n o r m a l i t i e s


6.

FRlSCH

d e t e c t e d . The g r o s s a u t o p s y r e v e a l e d no


69


and m i c r o s c o p i c f i n d i n g s i n t i s s u e s t a k e n at pattern of polymer-induced systemic toxicity.

In a s t u d y w i t h a l b i n o r a t s s p e c i m e n s o f t e s t m a t e r i a l s were i m p l a n t e d i n a g r o u p o f 100 r a t s , c o n s i s t i n g o f 50 m a l e s a n d 50 females. S i m i l a r g r o u p s , s e r v i n g as c o n t r o l s , r e c e i v e d implants o f USP p o l y e t h y l e n e a n d s h a m s u r g e r y o n l y . The s t u d y was c o n t i n ued for the lifetime of the animals, or 2 years, whichever occurred f i r s t . Mortality d a t a r e v e a l e d no s i g n i f i c a n t differences between test, treated control, or control groups with respect to the frequency o r number of deaths. There were no untoward b e h a v i o r a l r e a c t i o n s i n any of the a n i m a l s . Histopathol o g i c a l e v a l u a t i o n s r e v e a l e d t h a t t i s s u e changes found i n t r e a t e d r a t s were s i m i l a r to those i n c o n t r o l r a t s . The t y p e and incidence of neoplasms observed were considered normal for the laboratory r a t s o f t h e age and s t r a i n i n v o l v e d in this study. None o f t h e n e o p l a s m s o b s e r v e d w e r e a t t r i b u t a b l e to the experimental procedures. B i o d u r a b i l i t y was a s s e s s e d by a 2 - y e a r s u b c u t a n e o u s implantat i o n s t u d y i n dogs ( 8 ) . The s t u d y f o u n d no s i g n i f i c a n t c h a n g e s in physical properties of s i l i c o n e e l a s t o m e r as a r e s u l t of 2 years of subcutaneous implantation. Thus, medical grade silicone elastomers are biodurable, noncytotoxic, nonallergenic, nonpyrogenic, noncarcinogenic, nontoxic, and nonirritating. When implanted, the reaction is l i m i t e d to a m i l d foreign-body r e a c t i o n and e n c a p s u l a t i o n o f the i m p l a n t i n f i b r o u s t i s s u e as a normal p h y s i o l o g i c a l r e s p o n s e . Physical

Properties

of

Medical

Grade

Silicone

Elastomers

The e a r l i e r 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 v a r i e d p r i m a r i l y i n durometer ( S h o r e A , ASTM 2 2 4 0 ) f r o m a l o w o f a b o u t 30 t o a h i g h o f a b o u t 70 ( s o f t , m e d i u m a n d f i r m g r a d e s ) . D u r o m e t e r was v a r i e d primarily by increasing or decreasing filler content. Other p h y s i c a l p r o p e r t i e s v a r i e d e s s e n t i a l l y as e x p e c t e d . H o w e v e r , as t h e e l a s t o m e r s became u s e d i n a p p l i c a t i o n s w h e r e p h y s i c a l propert y r e q u i r e m e n t s were more d e m a n d i n g , s u c h as i n t h e i m p l a n t s u s e d i n b o n e a n d j o i n t r e c o n s t r u c t i o n [9) the performance of convent i o n a l m e d i c a l g r a d e e l a s t o m e r s was no l o n g e r adequate. Technology for substantially increasing tear propagation strength and resistance to flaw propagation during fatigue f l e x i n g was d e v e l o p e d i n t h e e a r l y 1 9 7 0 ' s a l l o w i n g t h e development o f m e d i c a l g r a d e h i g h p e r f o r m a n c e s i l i c o n e e l a s t o m e r . Crack growth r e s i s t a n c e e v a l u a t i o n s w e r e d o n e by ASTM D 8 1 3 . In this t e s t a DeMattia specimen i s f a t i g u e f l e x e d s h a r p l y at the precut f l e x i o n groove through a 180° bend. The g r o w t h o f an initial through-and-through 2 MÏ\ (0.080 inch) cut i s monitored as the specimen i s f l e x e d 10 cycles, or u n t i l the c u t grows t o 12.7 mm (0.5) whichever occurs first. With conventional medium hardness medical grade s i l i c o n e elastomer the length of the cut t y p i c a l l y e q u a l l e d or exceeded 12.7 mm a t 7 3 3 3 c y c l e s , w i t h an 9


70

POLYMERIC MATERIALS A N D ARTIFICIAL

extrapolated inches)

cat

per

10

rate

equal

By

silicone

elastomer

2.5

inch)

10

mm

(0.1

in

high

Table

studies

testing,

was

made

cut

was

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a

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the from

1459

medical cut

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growth

rate

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properties

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the

and

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the

were

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were

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become

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implants

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acute

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The

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90,000

million

finger

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axis

by

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9

implants

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was

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evaluations,

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size

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completely

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were

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(reduced

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ORGANS

Swanson

to

grade

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in

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{9)

3-8). Applications Artificial have

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allowed

conditions

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implants

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treatment

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variety

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elastomer

human is

health

otherwise

available. Plastic The

& Reconstructive implants used i n

Surgery p l a s t i c and

as space-occupying tissue that r e s u l t in contour or

reconstructive

and organ s u b s t i t u t e s cosmetic changes. The

surgery

serve

in applications h a r d n e s s c a n be

v a r i e d w i t h i n l i m i t s to simulate the t e x t u r e of t i s s u e s r e p l a c e d . Implants used in reconstruction of the nose and chin (11,12) ( F i g u r e s 9-11) are u s u a l l y r e l a t i v e l y f i r m to s i m u l a t e bone. The ear implant (13) (Figures 12-14) cartilage. The implants used for

is flexible to simulate breast reconstruction (14)

(Figures 15-20) typically contain a solid, thin silicone e l a s t o m e r e n v e l o p e ( f a b r i c a t e d from d i s p e r s i o n ) and f i l l e d w i t h a s o f t , c r o s s - l i n k e d s i l i c o n e gel to simulate the t e x t u r e of breast tissue. Custom i m p l a n t s from e i t h e r s o l i d s i l i c o n e e l a s t o m e r , or of the silicone gel type may also be prepared to meet o n e - o f - a - k i n d c o n t o u r needs w i t h s p e c i f i c p a t i e n t s . Ophthalmology Silicone elastomer

in

both

solid

and

sponge

form

is

used


as

a


I.

Typical

growth,

10

Durometer, Shore A Specific gravity

Crack

Tensile Elongation M o d u l u s a t 100% Tear, Die C Tear, Die B g

Property

Table

cycles 52 1.15

psi)

D2240 D924

(1200

700% 2 . 4 1 3 MPa ( 3 5 0 p s i ) 5 2 . 5 4 k N/m ( 3 0 0 p p i ) 5 2 . 5 4 k N/m ( 3 0 0 p p i ) 2 . 5 mm ( 0 . 1 inch)

D412 D412 D624 D624 D813

MPa

8.274

D412

Performance

High

ASTM

Medium

Hardness

Performance

1.14

6.895 MPa(1000psi) 500% 2 . 0 6 8 MPa ( 3 0 0 p s i ) Varies widely 13.13 k N/m(75ppi) 1459 ( 5 7 . 3 inch), Extrapolated 50

P h y s i c a l P r o p e r t i e s of Medical Grade High and C o n v e n t i o n a l S i l i c o n e Elastomer


ORGANS



F i g u r e 3. T y p i c a l a p p e a r a n c e o f a hand d e f o r m e d by r h e u m a t o i d a r t h r i t i s and a c a n d i d a t e f o r r e c o n s t r u c t i o n by implant resection arthroplasty. U l n a r d e v i a t i o n and s u b l u x a t i o n i n t h e m e t a t a r s o p h a l a n g e a l j o i n t s , and d e f o r m i t y o f t h e thumb a r e evident.



6.

FRISCH

Silicones in Artificial

73

Organs

F i g u r e 4. An x - r a y o f t h e hand shown i n F i g u r e i l l u s t r a t e s the extent of the deformities.

3

clearly



74


Figure

5.

Flexible

hinge

by A l f r e d B. S w a n s o n , diseased or destroyed

finger

d u r a b i l i t y of these implants i s the l o a d - d i s t r i b u t i n g h i n g e and resistance elastomer.

of

medical

joint

M.D. f o r use i n finger joints.

grade

high

implants

ORGANS

designed

reconstruction of The h i g h f l e x u r a l

derived from the f l e x u r a l performance

the design fatigue silicone


of


6.

FRISCH


Organs

Figure 6. S u r g i c a l placement of the f l e x i b l e hinge f i n g e r j o i n t implant. The m e t a c a r p a l head i s removed t o c r e a t e an a p p r o p r i a t e j o i n t s p a c e a n d t h e i n t r a m e d u l l a r y c a n a l s are then prepared to accept the implant stems. When t h e i m p l a n t i s p l a c e d i n p o s i t i o n t h e stems f i t s e c u r e l y i n the i n t r a m e d u l l a r y canals with the f l e x i b l e hinge permitt i n g 9 0 ° a c t i v e m o t i o n . J o i n t s p a c e i s m a i n t a i n e d by t r a n s f e r of the compressive forces of j o i n t motion across the implant t o c o r t i c a l bone. Careful attention to r e c o n s t r u c t i o n s o f t e n d o n s , l i g a m e n t s , and j o i n t c a p s u l e s and p o s t o p e r a t i v e t h e r a p y a r e v e r y i m p o r t a n t i n t h i s procedure.


75



F i g u r e 7. A p p e a r a n c e o f t h e hand reconstruction. T h e h a n d now h a s appearance, i s p a i n - f r e e , mobile,

shown i n F i g u r e 3 a f t e r e s s e n t i a l l y a normal and f u n c t i o n a l .



FRISCH


Organs

F i g u r e 8. An x - r a y o f t h e hand shown i n F i g u r e 7 w i t h i m plants i n a l l of the metatarsophalangeal j o i n t s . Correct i o n o f d e f o r m i t y i n t h e thumb i n c l u d e d f u s i o n o f t h e interphalangeal j o i n t to provide a strong pinch strength. Postoperatively, the patient returned to gainful employment. T h e i l l u s t r a t i o n s s h o w n i n F i g u r e s 3-8 a r e c o u r t e s y A l f r e d B. Swanson, M.D.



78


F i g u r e 9. Chin i m p l a n t s molded from medical cone e l a s t o m e r to i n c r e a s e the p r o j e c t i o n of

grade s i l i the mandible.


FRISCH


Organs


6.

Figure 10. P r e o p e r a t i v e a p p e a r a n c e o f a p a t i e n t who b e l i e v e d h e r q u a l i t y o f l i f e w o u l d be i m p r o v e d by a c h i n augmentation.


79



Figure shown

11. in

Postoperative Figure

appearance

of

the

same

patient

10.



6.

FRISCH


Organs

Figure 12. An e a r i m p l a n t m o l d e d f r o m m e d i c a l grade s i l i c o n e elastomer and used as a r t i f i c i a l c a r t i l a g e i n e a r reconstruction.


81



F i g u r e 13. Preoperative missing ear.

appearance

of

a child

with


a


Organs


FRISCH

F i g u r e 14. P o s t o p e r a t i v e a p p e a r a n c e o f t h e same c h i l d s h o w n i n F i g u r e 13 f o l l o w i n g e a r r e c o n s t r u c t i o n w i t h t h e silicone elastomer implant. H i s own s u b c u t a n e o u s t i s s u e and s k i n were shaped a r o u n d t h e s i l i c o n e framework d u r i n g the process of e a r r e c o n s t r u c t i o n .



84


F i g u r e 15. P r e o p e r a t i v e a p p e a r a n c e o f a p a t i e n t who h a s undergone a u n i l a t e r a l mastectomy f o r carcinoma of the breast.



FRISCH


Organs

Figure 16. A p p e a r a n c e o f t h e p a t i e n t s h o w n i n F i g u r e 16 f o l l o w i n g r e c o n s t r u c t i o n o f a b r e a s t shape w i t h a s i l i c o n e - g e l t y p e mammary i m p l a n t . T h e n i p p l e may b e r e c o n s t r u c t e d by e i t h e r a s p l i t t h i c k n e s s s k i n g r a f t from t h e r e m a i n i n g n i p p l e , o r t h e c o l o r c a n be e s t a b l i s h e d by tattooing.




F i g u r e 17. Preoperative appearance of a patient with c h r o n i c c y s t i c m a s t i t i s and a f a m i l y h i s t o r y o f b r e a s t c a n c e r , making h e r a h i g h r i s k p a t i e n t and a c a n d i d a t e p r o p h y l a c t i c subcutaneous mastectomy to substantively reduce the p o t e n t i a l of developing carcinoma of the breast.


for


FRISCH


Organs

Figure 18. P o s t o p e r a t i v e a p p e a r a n c e o f t h e p a t i e n t shown i n F i g u r e 17 f o l l o w i n g s i m p l e s u b c u t a n e o u s m a s t e c t o m y w i t h r e p l a c e m e n t o f b r e a s t t i s s u e by s i l i c o n e - g e l mammary implants.



88


Figure patient

19. who

Preoperative has

not

appearance

developed

normal

of

an

adult

female

female

breast

con-

tour.



FRISCH


Organs

Figure 20. P o s t o p e r a t i v e a p p e a r a n c e o f t h e p a t i e n t shown i n F i g u r e 19 f o l l o w i n g b r e a s t r e c o n s t r u c t i o n w i t h s i l i c o n e - g e l mammary i m p l a n t s .


90



space-occupying implant to buckle the s c l e r a f o r treatment of a d e t a c h e d r e t i n a (10) (Figures 21-22). S i l i c o n e implants are used in r e p a i r i n g f r a c t u r e of the f l o o r of the o r b i t . Space-occupying implants are a l s o used f o l l o w i n g e n u c l e a t i o n to f i l l or adjust t h e v o i d l e f t by removal o f t h e e y e , a l l o w i n g a p r o s t h e t i c eye t o be w o r n . S i l i c o n e elastomer tubes are often used to restore patency to blocked or destroyed l a c r i m a l ducts. Orthopaedic Surgery A v a r i e t y o f f l e x i b l e 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 have been d e v e l o p e d (9) f o r r e c o n s t r u c t i o n o f d i s e a s e d o r d e s t r o y e d s m a l l j o i n t s of the body. A t o t a l o f 14 d i f f e r e n t i m p l a n t s h a v e b e e n developed, each in a range of sizes, for reconstruction of f i n g e r s , thumbs, w r i s t s , e l b o w s , and f e e t . The d e v i c e s i n c l u d e a p a s s i v e tendon implant used i n 2-stage procedures f o r r e c o n s t r u c tion of tendons. Finger, wrist, and t o e joint implants are available with f l e x i b l e hinges. A l l bone and j o i n t i m p l a n t s have intramedullary stems which a i d i n p o s i t i o n i n g the i m p l a n t s and help maintain the implant spacer i n c o r r e c t anatomical position. The i m p l a n t s a r e f a b r i c a t e d f r o m m e d i c a l g r a d e h i g h performance s i l i c o n e e l a s t o m e r t o p r o v i d e maximum d u r a b i l i t y . Cardiovascular Surgery One o f t h e e a r l i e s t u s e s o f 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 i n c a r d i o v a s c u l a r s u r g e r y was f o r t h e b a l l i n the ball-and-cage heart valve (Figure 23). In the early I960's some o f these valves f a i l e d because of s w e l l i n g of the s i l i c o n e elastomer b a l l s due t o a b s o r p t i o n o f l i p i d - t y p e s u b s t a n c e s f r o m t h e b l o o d . This resulted in e i t h e r loss of b a l l motion because of a t i g h t f i t w i t h i n the cage, or fragmentation of the b a l l s . However; the d i f f i c u l t i e s were t r a c e d to improper p r o c e s s i n g of the s i l i c o n e e l a s t o m e r , and when t h e s e p r o c e s s i n g d i f f i c u l t i e s w e r e c o r r e c t e d these types of problems with s i l i c o n e elastomer heart valve b a l l s have not r e c u r r e d . O t h e r c a r d i o v a s c u l a r u s e s have i n c l u d e d c o a t i n g s on pacemakers and pacemaker l e a d - w i r e s f o r purposes o f i n s u l a t i o n and for achieving biocompatibility. Medical grade s i l i c o n e elastomer has been w i d e l y used as a m a t e r i a l o f c o n s t r u c t i o n i n e x p e r i m e n t a l a r t i f i c i a l h e a r t s and h e a r t a s s i s t d e v i c e s . Silicone tubing is often preferred for use i n r o l l e r - t y p e b l o o d pumps during cardiopulmonary bypass. Medical grade s i l i c o n e elastomer cont a i n s no l e a c h a b l e o r o r g a n i c p l a s t i c i z e r s a n d t h u s contributes minimal contamination in blood contact a p p l i c a t i o n s . Medical

Applications

for

Silicone

Fluid

The b i o m e d i c a l c h a r a c t e r i s t i c s o f m e d i c a l g r a d e s i l i c o n e f l u i d (liquid polydimethylsiloxanes) have become w i d e l y misunderstood. This i s p r i m a r i l y because of the p u b l i c i t y given i n both the l a y and p r o f e s s i o n a l p r e s s to c o m p l i c a t i o n s a r i s i n g from " s i l i c o n e



FRISCH


Sclera F i g u r e 21. Drawing o f a c r o s s - s e c t i o n o f an eye w i t h detached r e t i n a which t y p i c a l l y r e s u l t s in loss of v i s i o n and r e t i n a l d e t e r i o r a t i o n .

F i g u r e 22. C o r r e c t i o n o f d e t a c h e d r e t i n a by s c l e r a l buckling. A s i l i c o n e e l a s t o m e r band c o m p l e t e l y e n c i r c l e s the eye to i n c r e a s e i n t r a o c c u l a r p r e s s u r e . An e x t r a pad o f m e d i c a l grade s i l i c o n e i s o f t e n used beneath the band at the p o i n t of detachment i n order to buckle the s c l e r a inward and p l a c e i t i n c o n t a c t w i t h the r e t i n a . Reattachm e n t may b e e n c o u r a g e d b y l a s e r b e a m o r d i a t h e r m y s t i m u l a tion.




Figure 23. Ball-and-cage heart valves constructed with silicone elastomer b a l l s . Compared t o metal o r r i g i d p l a s t i c b a l l s , s i l i c o n e e l a s t o m e r b a l l s c r e a t e no n o i s e a s the heart beats. Problems from s w e l l i n g and fragmentation of the b a l l s which o c c u r r e d i n a few p a t i e n t s i n the m i d - 1 9 6 0 ' s were t r a c e a b l e to the p r o c e s s i n g t e c h n i q u e s u s e d i n f a b r i c a t i n g b a l l s , and when o n c e c o r r e c t e d t h e problems have not r e c u r r e d . S i l i c o n e b a l l s c o n t i n u e t o be used i n heart v a l v e s .


6.

FRISCH


93


fluid" injections. Injection is a serious misuse since no manufacturer recommends i n j e c t i o n as a use f o r silicone fluid, a n d no s i l i c o n e f l u i d h a s b e e n a p p r o v e d v i a t h e FDA premarket a p p r o v a l a p p l i c a t i o n p r o c e s s f o r u s e a s an i n j e c t a b l e . Furthermore, many o f t h e c o m p l i c a t i o n s r e s u l t e d f r o m t h e i n j e c t i o n of n o n - s i l i c o n e o r i n d u s t r i a l s i l i c o n e m a t e r i a l s and were done under uncontrolled, s c i e n t i f i c a l l y unsound conditions. Those making the i n j e c t i o n s t y p i c a l l y represented to t h e i r p a t i e n t s that the material being injected was "medical grade silicone fluid" without regard for i t s actual composition. Essentially a l l i n j e c t i o n misuses involved subdermal injection for purposes of soft tissue augmentation. Many o f the c o m p l i c a t i o n s r e p o r t e d were a s s o c i a t e d w i t h i n j e c t i o n s i n t o the female breast. By c o m p a r i s o n , i n c o n t r o l l e d c l i n i c a l investigat i o n s (where i n j e c t i o n s i n t o the female b r e a s t were s p e c i f i c a l l y excluded), done i n k e e p i n g w i t h r e g u l a t o r y procedures, clinical e v i d e n c e has s u g g e s t e d t h a t m e d i c a l grade s i l i c o n e f l u i d may, in s e l e c t e d c a s e s p r o p e r l y d o n e by a t r a i n e d p h y s i c i a n , be reasona b l y s a f e and e f f e c t i v e for soft t i s s u e augmentation by injection. However; a d e m o n s t r a t i o n o f s a f e t y and e f f i c a c y as r e q u i r ed for premarket approval by FDA has not been accomplished. Accordingly, no s i l i c o n e f l u i d s h o u l d be a d m i n i s t e r e d t o humans by i n j e c t i o n f o r any p u r p o s e u n l e s s done as p a r t o f a c o n t r o l l e d clinical investigation and done in keeping with all of the regulatory provisions. In t h e i n t e r i m t h e r e a r e o t h e r i m p o r t a n t h e a l t h c a r e a p p l i c a tions for silicone fluids. Many o f t h e s e i n v o l v e i t s use as a lubricant. The a v a i l a b i l i t y o f s i l i c o n e f l u i d as a l u b r i c a n t for u s e on d i s p o s a b l e h y p o d e r m i c n e e d l e s ( F i g u r e 24) contributed to the development of the d i s p o s a b l e hypodermic needle. Essentially all d i s p o s a b l e hypodermic needles are l u b r i c a t e d with silicone f l u i d t o p e r m i t e a s y i n s e r t i o n and r e m o v a l , and t o m i n i m i z e pain. P r i o r to the use of s i l i c o n e f l u i d l u b r i c a n t s d i s p o s a b l e needles tended to be very painful and sometimes broke or bent upon insertion. S i l i c o n e f l u i d i s a l s o used to l u b r i c a t e d i s p o s a b l e hypodermic s y r i n g e s ( F i g u r e 25). Without a suitable lubricant it is u n l i k e l y t h a t t h e d i s p o s a b l e h y p o d e r m i c s y r i n g e w o u l d h a v e become available. Silicone fluid lubricants allow the rubber plunger tip to slide easily down t h e molded plastic barrel while it continues to provide a tight seal to prevent leakage of the material being injected or inflow of air upon aspiration. S y r i n g e s t h u s l u b r i c a t e d may b e s t o r e d f o r l o n g p e r i o d s o f time w i t h o u t change i n the l u b r i c i t y p r o p e r t i e s o r the f o r c e required for plunger movement, very important considerations in the control over the speed and volume w i t h which injections are given. W i t h each i n j e c t i o n a s m a l l amount o f s i l i c o n e i s deposited in the patient's tissue from the needle, and also from the syringe. However; studies (JL5) suggest that in these small




F i g u r e 24. Disposable hypodermic needle l u b r i c a t e d with silicone fluid. The u s e o f m e d i c a l g r a d e s i l i c o n e f l u i d l u b r i c a n t s m i n i m i z e p a i n and p e r m i t n e e d l e s t o be i n s e r t e d and w i t h d r a w n from t i s s u e w i t h m i n i m a l f o r c e and w i t h o u t breakage or bending.



FRISCH


Figure 25. D i s p o s a b l e h y p o d e r m i c s y r i n g e w a s made p o s s i b l e by t h e a v a i l a b i l i t y o f m e d i c a l g r a d e s i l i c o n e f l u i d t o l u b r i c a t e the plunger. W i t h o u t an a p p r o p r i a t e l u b r i c a n t i t w o u l d be e s s e n t i a l l y i m p o s s i b l e t o move t h e p l u n g e r t i p i n s i d e the molded p l a s t i c b a r r e l . S i l i c o n e f l u i d does not d e t e r i o r a t e w i t h t i m e , t h u s s y r i n g e s may b e s t o r e d f o r long p e r i o d s of time w i t h o u t change i n the f o r c e s r e q u i r e d t o move t h e p l u n g e r w i t h i n t h e b a r r e l .


96


quantities patients

silicone who

suffering

from

must

fluids receive

elicit

adverse

effect,

frequently

such

even as

with those

diabetes. D I S C U S S I O N AND


no

injections

CONCLUSIONS

A r t i f i c i a l organs and i m p l a n t s to r e p l a c e d i s e a s e d , d e f e c t i v e , o r d e s t r o y e d c o m p o n e n t s o f t h e b o d y a r e u s e d by e s s e n t i a l l y e v e r y medical s p e c i a l t y . Medical grade s i l i c o n e elastomer i s the only e l a s t o m e r g e n e r a l l y r e c o g n i z e d as s a f e and e f f e c t i v e as a m a t e r ial of construction for soft, f l e x i b l e , elastomeric implants. C a r e f u l l y c o n t r o l l e d f o r m u l a t i o n s have been q u a l i f i e d by c h r o n i c biocompatibility and b i o d u r a b i l i t y studies to provide a soft, flexible, e l a s t o m e r i c m a t e r i a l o f c o n s t r u c t i o n t o m e e t many of the needs i n t h e s e a p p l i c a t i o n s .

Literature Cited 1. F. S. Kipping, "Organic derivatives of silicon, Part II: The synthesis of benzylethylpropylsilicol, its sulfonation, and resolution of the D-L sulfonic derivatives into its optically active components", J. Chem. Soc. 91:209-240, 1907. 2. V. K. Rowe, H. C. Spencer, and S. L. Bass, "Toxicological studies on certain commercial silicones", J. Indust. Hyg. Tox. 30(6):332-352, Nov. 1948. 3. V. K. Rowe, H. C. Spencer, and S. L. Bass, "Toxicologic studies on certain commercial silicones", Arch. Indust. Hyg. Occup. Med. 1:539-544, May 1950. 4. J. Holter, "A father's last-chance invention saves his son", Reprint from The Reader's Digest, Jan. 1957. 5. R. E. Wilsnack, "Quantitative cell culture biocompatibility testing of medical devices and correlation to animal tests", Biomater. Med. Devices Artif. Organs 4(3 & 4):235-261, 1976. 6. R. E. Wilsnack, F. S. Meyer, and J. G. Smith, "Human cell culture toxicity testing of medical devices and correlation to animal tests", Biomater. Med. Devices Artif. Organs 1(3):543-562, 1973. 7. ASTM F748, "Recommended Practices for Selecting Generic Biological Test Methods for Materials and Devices", ASTM Standards for Medical and Surgical Materials and Devices. 8. J. W. Swanson and J. E. LeBeau, "The effect of implantation on the physical properties of silicone rubber", J. Biomed. Mater. Res. 8:357-367, 1974. 9. A. B. Swanson, "Flexible implant resection arthroplasty in the hand and extremities, The C. V. Mosby Co., St. Louis, 1973. 10. H. A. Lincoff, I. Baras, and J. McLean, "Modifications of the Custodis procedure for retinal detachment", Arch. Ophthalmol. 73:160-163, 1965.


6.

FRISCH

97


11. J. Safian, "Progress in nasal and chin augmentation", Plast. Reconstr. Surg. 7:446-452, 1966. 12. G. B. Snyder, E. H. Courtiss, Β. M. Kaye, and G. P. Gradinger, "A new chin implant for microgenia", Plast. Reconstr. Surg. 61:854-860, 1978. 13. T. D. Cronin, "Use of a Silastic frame for total and subtotal reconstruction of the external ear: preliminary report", Plast. Reconstr. Surg. 37(5):399-405, May 1966. 14. T. D. Cronin and F. J. Gerow, "Augmentation mammaplasty: a new 'natural feel' prosthesis", Excerpta Medica International Congress, Series No. 66, Proceedings of the Third International Congress of Plastic Surgery, Washington, D.C., pp. 41-49, Oct. 1963. 15. C. H. Hine, H. W. Elliott, R. R. Wright, R. D. Cavalli, and C. D. Porter, "Evaluation of a Silicone Lubricant Injected Spinally", Toxicol. Appl. Pharmacol. 15, 566-573 (1969).


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March 19, 1984


Silicones in Artificial Organs - ACS Symposium Series (ACS

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