The Basics of Artificial Organs - American Chemical Society

1 The Basics of Artificial Organs C H A R L E S G. G E B E L E I N

Downloaded by KANSAS STATE UNIV on November 13, 2014 | http://pubs.acs.org Publication Date: June 8, 1984 | doi: 10.1021/bk-1984-0256.ch001

Department of Chemistry, Youngstown State University, Youngstown, O H 44555

The primary purpose of this paper is to review the types of devices that are currently used in the human body as artificial organs and prosthetic devices. By definition, an organ is a specialized structure (e.g. heart, kidney, limb, leaf, flower) in an animal or a plant that can perform some specialized function. Most parts of the human body can be classed as organs. These varied parts sometimes become defective and must be replaced by an artifical organ or a prosthetic device. In almost all cases, these replacement devices are constructed of natural or synthetic polymeric materials. Such biomaterials must exhibit good compatibility with the blood and the body fluids and tissues with which they come into contact. In addition, the artificial device must closely duplicate the function of the natural organ. In practice, these artificial devices are constructed from a wide variety of materials such as metals, ceramics (including glass and carbon), natural tissues (actually polymeric in nature), and synthetic polymers. Partly due to the wider range of properties available, most of these artificial devices are constructed wholely or partly from natural or synthetic polymers. Obviously the same polymer could not be used for all possible artificial organs or prosthetic devices. Rather, the material to be used must be matched to the specific use requirements. Artificial organs can conveniently be classed into four groups: (I) Bone/Joint Replacements (e.g. hip, knee, finger, total limb), (II) Skin/Soft Tissue Replacements (e.g. skin, breast, muscle), (III) Internal Organs (e.g. heart, kidney, blood vessels, liver, pancreas), and (IV) Sensory Organs (e.g. eye, ear). This paper will consider the basic requirements for some of these artificial organs and will discuss the 0097-6156/ 84/ 0256 0001 $06.00/ 0 © 1984 American Chemical Society

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

2

POLYMERIC MATERIALS A N D ARTIFICIAL ORGANS


various polymeric materials that are used. The greatest emphasis will be on the chemistry and biomaterial requirements of the artificial internal organs. The primary purpose o f t h i s chapter i s t o review t h e types of devices t h a t a r e being used i n t h e human body a t t h e present time as a r t i f i c i a l organs, p r o s t h e t i c devices or general implants. Subsequent chapters i n t h i s book w i l l consider some o f these d e v i c e s , e t c . i n more d e t a i l . I n a s i m i l a r manner, other papers consider t h e various polymeric and non-polymeric m a t e r i a l s t h a t are used and d i s c u s s t h e s p e c i a l i z e d requirements f o r these app l i c a t i o n s . These areas a r e covered i n t h i s paper o n l y s l i g h t l y s i n c e they a r e d i s c u s s e d i n d e t a i l elsewhere. An a r t i f i c i a l organ c l e a r l y i s a replacement f o r a n a t u r a l organ i n t h e body. The d i c t i o n a r y d e f i n e s an organ as "a d i f f e r e n t i a t e d s t r u c t u r e (as a h e a r t , kidney, l e a f , flower) i n an animal or p l a n t made up o f various c e l l s and t i s s u e s and adapted for t h e performance o f some s p e c i f i c f u n c t i o n . . . " Although t h i s d e f i n i t i o n might be modified somewhat i n a medical textbook, i t w i l l serve t o cover and i l l u s t r a t e t h e range i n a p p l i c a t i o n s and p r o p e r t i e s t h a t occur i n t h i s r a t h e r s p e c i a l i z e d f i e l d . Most parts o f t h e human body can be c l a s s e d as an organ by t h i s d e f i n i t i o n and c o u l d , p o t e n t i a l l y , be r e p l a c e d by an a r t i f i c i a l organ or by a p r o s t h e t i c / b i o m e d i c a l d e v i c e . This c o n s t i t u t e s a very broad range o f f u n c t i o n s and p r o p e r t i e s which a r e o f t e n o f an opposing nature and hundreds o f s p e c i f i c devices have been t r i e d as replacement p a r t s , o f t e n w i t h l i m i t e d success. P a r t o f t h i s problem i s due t o t h e f a c t t h a t t h e requirements f o r each device a r e h i g h l y s p e c i f i c and t h e m a t e r i a l s used must meet these v a r i e d s p e c i f i c a t i o n s . Obviously, t h e m a t e r i a l used t o r e p l a c e a bone or a j o i n t would not be a l i k e l y candidate f o r an a r t i f i c i a l s k i n or a s o f t t i s s u e replacement merely on t h e b a s i s o f t h e d i f f e r e n t p h y s i c a l c h a r a c t e r i s t i c s o f each type o f b i o m a t e r i a l . Superimposed on t h i s general requirement i s t h e f a c t t h a t t h e body has been designed t o d e t e c t , a t t a c k and/or r e j e c t any f o r e i g n m a t e r i a l s t h a t come i n t o contact w i t h t h e bodies t i s s u e s and most s y n t h e t i c m a t e r i a l s a r e not compatible w i t h t h e v a r i o u s t i s s u e s , f l u i d and t h e blood o f t h e human body. N a t u r a l mater i a l s , on t h e other hand, u s u a l l y e l i c i t an even more severe r e j e c t i o n response from t h e body although some n a t u r a l t i s s u e s have been modified by v a r i o u s chemical treatments which enable them t o be t o l e r a t e d t o some extent (e.g. treatment o f r e p l a c e ment porcine heart valves w i t h g l y c e r o l or an aldehyde). This problem i s e s p e c i a l l y evident i n the r e l a t e d area o f organ t r a n s p l a n t a t i o n . P a r t l y f o r t h i s reason, e s s e n t i a l l y a l l t h e a r t i f i c i a l organs, p r o s t h e t i c devices and/or implants a r e made from ceramics (which could a l s o i n c l u d e v a r i o u s glasses and some s p e c i a l forms o f carbon), metals or s y n t h e t i c polymers. Because the polymeric m a t e r i a l s (both n a t u r a l and s y n t h e t i c ) have a wider


1.

GEBELEIN

The Basics of Artificial

Organs

3


range o f p r o p e r t i e s t h a t are needed i n these v a r i e d a p p l i c a t i o n s , and because they are a l s o more compatible, i n some cases, w i t h the body t i s s u e s than the other c l a s s e s o f m a t e r i a l s , polymers are the most w i d e l y used type o f m a t e r i a l i n t h i s f i e l d . I t i s not p o s s i b l e t o cover a l l aspects o f a r t i f i c i a l organs i n t h i s short paper and f u r t h e r i n f o r m a t i o n and references can be found i n some recent review a r t i c l e s and books (1-18). I n t h i s paper we w i l l o u t l i n e the nature o f the devices and m a t e r i a l s c u r r e n t l y used as a r t i f i c i a l organs. For convenience these w i l l be subdivided i n t o the c a t e g o r i e s of: ( i ) Bone/Joint Replacement; ( I I ) S k i n / S o f t Tissue Replacements; ( i l l ) I n t e r n a l Organs; and (IV) Sensory Organs. Type ( i ) - Bone/Joint

Replacements

In many cases i t i s necessary t o r e p l a c e a d e f e c t i v e j o i n t w i t h a p r o s t h e t i c device t o a l l e v i a t e a c o n d i t i o n caused by an accident or a degenerative disease. J o i n t replacements must meet some s p e c i f i c requirements i n c l u d i n g : (a) maintainance o f normal j o i n t space; (b) good, steady, n a t u r a l motion; (c) f i r m and 'permanent' f i x a t i o n ; (d) r e a d i l y l u b r i c a t e d ; (e) s t r e s s and e r o s i o n r e s i s t a n t ; and ( f ) bi©compatibility. Most j o i n t replacements u t i l i z e polymers t o some extent. Finger j o i n t s u s u a l l y are replaced w i t h a p o l y ( d i m e t h y l s i l o x a n e ) i n s e r t and over ^00,000 such replacements are made each year ( l ) . More r e c e n t l y a poly(l,U-hexadiene) polymer has been t r i e d i n t h i s a p p l i c a t i o n ( l ) . Many other parts o f the hand, such as t h e bones, have a l s o been replaced by s i l i c o n e rubber. Other types of j o i n t s , such as the h i p or the knee, o f t e n i n v o l v e the contact of a metal b a l l o r r i d e r on a p l a s t i c s u r f a c e which i s u s u a l l y made from high d e n s i t y , high molecular weight polyethylene. These metal and p l a s t i c parts are u s u a l l y anchored i n the body u s i n g a 'cement' o f poly(methyl methacrylate) which i s polymerized i n s i t u . F u l l and p a r t i a l h i p prostheses are implanted about 250,000 times a n n u a l l y w h i l e the knee replacement occurs about 100,000 times each year ( 5 ) . The major problems t h a t occur i n j o i n t replacement are: (a) wear w i t h p a t i e n t i r r i t a t i o n due t o the d e b r i s , and (b) loosening o f the p r o s t h e s i s which r e s u l t s i n unsteady motion and increased wear ( l , 19, 2 0 ) . I n some cases, i n j u r y , genetic defects or sickness r e q u i r e s the complete or p a r t i a l replacement o f an upper or lower limb. The d i f f i c u l t y o f o b t a i n i n g an adequately working p r o s t h e s i s increases markedly w i t h the amount o f the limb t h a t must be r e p l a c e d . I n other words, i t i s more d i f f i c u l t t o design a s a t i s f a c t o r y p r o s t h e s i s f o r an arm than f o r a hand. I n a d d i t i o n , f u n c t i o n a l lower limb r e p l a c e ments are more d i f f i c u l t t o achieve than are upper limb r e p l a c e ments. This i s due, i n p a r t , t o the f a c t t h a t w h i l e many o f the upper limb f u n c t i o n s can be done w i t h only one limb, the primary f u n c t i o n o f the lower l i m b s , walking, cannot. A number o f p a r t i a l or t o t a l prostheses do, however, e x i s t f o r lower limb replacement


4

POLYMERIC MATERIALS AND

ARTIFICIAL ORGANS

which can be u t i l i z e d t o permit a reasonable degree of locomot i o n . Some of these devices u t i l i z e h y d r a u l i c knee j o i n t s as p a r t of the design (21-2U). Upper limb replacement can be e i t h e r cosmetic and/or f u n c t i o n a l . Normally when only one upper limb i s r e p l a c e d , the p a t i e n t does the m a j o r i t y of limb f u n c t i o n s w i t h the other l i m b , even when t h i s had been the non-dominant arm, because the a r t i f i c i a l limb does not f u n c t i o n n e a r l y as w e l l as the n a t u r a l one. The more recent m y o e l e c t r i c a c t i v a t e d devices show much promise toward d u p l i c a t i n g the f u n c t i o n of a n a t u r a l arm or hand but much remains t o be done i n t h i s area (2^-26).


Type ( I I ) - S k i n / S o f t Tissue Replacement The s k i n i s the l a r g e s t organ i n the body from the standp o i n t of weight or volume. At the present time t h e r e i s no m a t e r i a l t h a t can d u p l i c a t e t h i s complex organ i n a l l i t s f u n c t i o n s but over 100,000 people are h o s p i t a l i z e d a n n u a l l y w i t h severe s k i n damage (burns, a c c i d e n t s , e t c . ) t h a t r e q u i r e s immediate treatment t o prevent gross b a c t e r i a l contamination and/or the l o s s of body f l u i d s and e l e c t r o l y t e s . The most promising approach t o t h i s problem has u t i l i z e d a composite system c o n s i s t i n g of a collagen-glycosaminoglycan inner membrane w i t h a s i l i c o n e rubber outer l a y e r (27). Other approaches have i n c l u d e d dextran hydrogels (28), v a r i o u s polypeptides (29), and c o l l a g e n (30). These m a t e r i a l s attempt t o d u p l i c a t e the b a r r i e r p r o p e r t i e s of the s k i n w i t h good success, but no m a t e r i a l has yet been a b l e t o d u p l i c a t e the other s k i n f u n c t i o n s and a t r u e a r t i f i c i a l s k i n does not yet e x i s t . A l a r g e p o r t i o n of the human body i s composed of s o f t t i s s u e s i n c l u d i n g muscles, f a t t y t i s s u e s and connective t i s s u e s . The general area of p l a s t i c and/or r e c o n s t r u c t i v e surgery i n v o l v e s t h i s type of t i s s u e t o a l a r g e extent. Each year t h e r e are a t l e a s t 200,000 breast prostheses and/or augumentations (T), 200,000 f a c i a l p l a s t i c s u r g e r i e s ( l ) , and 35,000 h e r n i a r e p a i r s conducted (15). A s a t i s f a c t o r y s o f t t i s s u e m a t e r i a l must have s u i t a b l e long-term, p h y s i c a l p r o p e r t i e s ( s o f t and/or r u b b e r y ) , and not cause any adverse e f f e c t i n the p a t i e n t . Very few m a t e r i a l s can meet these general (and some other s p e c i f i c ) r e quirements. For example, sponges and t e x t i l e s might have s u i t a b l e " s o f t n e s s " but the ingrowth of f i b r o u s t i s s u e q u i c k l y renders these m a t e r i a l s u n s a t i s f a c t o r y s i n c e the implant becomes more r i g i d or hard a f t e r t h i s ingrowth. While many m a t e r i a l s have been t r i e d f o r s o f t t i s s u e replacement, the most common one i s p o l y ( d i m e t h y l s i l o x a n e ) which can be made i n the form of rubbery g e l s , tubes and/or sheets w i t h v a r y i n g degrees of ' s t i f f n e s s produced by v a r y i n g l e v e l s of c r o s s l i n k i n g . Some l i m i t e d use has been found f o r p o l y e t h y l e n e , polyurethane and the s y n t h e t i c rubbers ( l , 15, 31-33). 1


1.

GEBELE1N


Organs

5


Type ( i l l ) - I n t e r n a l Organs The area o f a r t i f i c i a l i n t e r n a l organs i n c l u d e s t h e h e a r t , lungs, l i v e r , kidneys, pancreas, blood v e s s e l s and the g a s t r o i n t e s t i n a l t r a c t . I n a d d i t i o n t o t h e obvious requirements o f blood and t i s s u e c o m p a t i b i l i t y , these replacements o f t e n have h i g h l y s p e c i a l i z e d f u n c t i o n s which are almost impossible t o d u p l i c a t e w i t h man-made m a t e r i a l s . N e v e r t h e l e s s , i t i s o f t e n necessary t o augment or r e p l a c e t h e f u n c t i o n o f these organs. Over 100,000 pacemakers are implanted a n n u a l l y t o r e g u l a t e the heart beat and these devices a r e u s u a l l y polymer coated t o p r o t e c t t h e e l e c t r o n i c p o r t i o n s from t h e body f l u i d s . Pacemakers have been used e x p e r i m e n t a l l y i n animals s i n c e 1932 and have been used i n humans s i n c e 1952 t o t r e a t Stokes-Adams disease (heart b l o c k ) . Implantable pacemakers were f i r s t used i n 1958. The more recent v e r s i o n s o f these devices are capable o f v a r y i n g t h e heart beat r a t e (3^, 35). While t h e r e a r e four valves i n t h e h e a r t , almost a l l t h e replacements a r e done on e i t h e r t h e a o r t i c or m i t r a l v a l v e s . A wide v a r i e t y o f designs have been devised f o r these v a l v e r e placements u t i l i z i n g many n a t u r a l and s y n t h e t i c polymers. The major types o f m a t e r i a l s used are p o r c i n e v a l v e s , which have been p r e t r e a t e d w i t h g l y c e r o l or an aldehyde t o reduce immune responses, polymeric m a t e r i a l s , such as s i l i c o n e rubber, t e t r a f l u o r o e t h y l e n e and Dacron®, metals and some ceramics ( e s p e c i a l l y c e r t a i n types o f carbon). The most common designs f o r t h e devices u s i n g s y n t h e t i c polymers c o n t a i n a b a l l i n a cage or some form o f a d i s c i n a cage. I n some cases, human dura mater has been u t i l i z e d as a v a l v e m a t e r i a l . Over 30,000 heart v a l v e replacements a r e made a n n u a l l y . I n n e a r l y a l l cases, t h e p a t i e n t must r e c e i v e r e g u l a r a n t i - c o a g u l a n t medication f o r the remainder of t h e i r l i f e i n order t o avoid blood c l o t s ( l , 30, 36-38). In 1980, over 110,000 coronary a r t e r y bypass operations were performed i n t h e United States alone ( 5 ) . I n a d d i t i o n , t h e r e were a l a r g e number o f other blood v e s s e l replacements and/or r e p a i r s done w i t h t h e t o t a l being i n excess o f 200,000. While much o f t h i s surgery i s done u s i n g n a t u r a l m a t e r i a l s (autogeneous blood v e s s e l s when p o s s i b l e ) , a l a r g e p o r t i o n o f t h i s surgery u t i l i z e s s y n t h e t i c polymers. These a r e u s u a l l y Dacron®, i n t h e form o f k n i t t e d or woven tubes, or p o l y t e t r a f l u o r o e t h y l e n e , i n the form o f a 'micro-expanded tube.' While t h e n a t u r a l blood v e s s e l s might seem p r e f e r a b l e , i n cases of advanced disease t h e other v e s s e l s o f t h e body are o f t e n d e f e c t i v e and would not be s u i t a b l e replacement m a t e r i a l s . A good example would be t h e saphenous v e i n s , which are commonly used i n heart bypass surgery, but f r e q u e n t l y a r e t o o weak or blocked t o be used i n some p a t i e n t s . For t h i s reason s y n t h e t i c m a t e r i a l s a r e e s s e n t i a l . The use o f woven or k n i t t e d Dacron® blood v e s s e l prostheses dates from t h e p i o n e e r i n g work of DeBakey i n 1951 and t h i s m a t e r i a l i s f r e q u e n t l y t h e p r o s t h e s i s o f choice among many heart surgeons



6

POLYMERIC MATERIALS AND

ARTIFICIAL ORGANS

(39). These Dacron® prostheses can only be used f o r v e s s e l s 6 mm or l a r g e r . The mode of operation i n v o l v e s i m p l a n t i n g the prost h e s i s whose open pores r a p i d l y become f i l l e d or clogged w i t h a thrombus (blood c l o t ) which i s then g r a d u a l l y r e p l a c e d by a new t i s s u e c a l l e d neointima. I t i s t h i s neointima t h a t e v e n t u a l l y contacts the blood r a t h e r than the thrombogenic Dacron®. The neointima appears t o be s i m i l a r i n i t s composition t o the n a t u r a l blood v e s s e l m a t e r i a l . In tubes much s m a l l e r than 6 mm, the neointima blocks o f f the v e s s e l t o a great extent. The use of expanded t e t r a f l u o r o e t h y l e n e (PTFE) prostheses (Gore-Tex®) has permitted the replacement of v e s s e l s as s m a l l as k mm. The neointima l a y e r i s t h i n n e r i n t h i s system. E x p e r i mental work i n dogs has used PTFE v e s s e l s as s m a l l as 3 mm s u c c e s s f u l l y (k0 hi). U n f o r t u n a t e l y , most of the blood v e s s e l s i n the human body are s m a l l e r than t h i s s i z e and no s u i t a b l e m a t e r i a l i s yet a v a i l a b l e although many experimental m a t e r i a l s show considerable promise. These i n c l u d e various hydrogels (12) and c e r t a i n polyether polyurethane ureas (PEUUs) (^2, 43). Over a m i l l i o n deaths occur a n n u a l l y i n the USA due t o heart disease and over 500,000 are h o s p i t a l i z e d each year w i t h heart a t t a c k s ( l ) . C e r t a i n l y one of the most s p e c t a c u l a r type of operations i n v o l v e s the t o t a l replacement of the heart. Most g e n e r a l l y , t h i s i s done by means of a t r a n s p l a n t from a human donor. For obvious reasons, the replacement organ i s not r e a d i l y a v a i l a b l e . Animal hearts (or other organs) are r a p i d l y r e j e c t e d by the human body. Much research has been done t o develop a t o t a l a r t i f i c i a l heart (TAH) or a p a r t i a l a s s i s t device ( l e f t v e n t r i c u l a r a s s i s t d e v i c e ; LVAD) and some success has been achieved i n t h i s area. For example, cows have been kept a l i v e for over seven months w i t h a TAH. In most cases, the TAH c o n s i s t s of a p a i r of LVADs. The LVAD i t s e l f i s designed t o permit a p a r t i a l r e s t f o r a working heart and thereby permit h e a l i n g t o occur more r e a d i l y . While the LVADs and TAHs are u s u a l l y implanted, the devices are powered and c o n t r o l l e d e x t e r n a l l y . Many d i f f e r e n t polymeric m a t e r i a l s have been t r i e d i n these d e v i c e s , but the most w i d e l y used one, at present, i s a p o l y e t h e r p o l y urethane which i s used i n the pumping diaphram and the l i n i n g of the pump chamber which contacts the blood. This polyether p o l y urethane has f a i r blood c o m p a t i b i l i t y and does show s u f f i c i e n t d u r a b i l i t y t o undergo the 36+ m i l l i o n f l e x i n g s which would occur i n a blood pump each year of use. (Most m a t e r i a l s cannot achieve t h i s v a l u e ; the d e s i r e d d u r a t i o n of use i s p r o j e c t e d t o be at l e a s t t e n y e a r s , or 360+ m i l l i o n f l e x i n g s . ) Other s y n t h e t i c polymers t h a t have been t r i e d f o r t h i s a p p l i c a t i o n i n c l u d e s i l i c o n e rubber, p o l y v i n y l c h l o r i d e ( p l a s t i c i z e d ) , n a t u r a l rubber and some s y n t h e t i c rubbers such as p o l y ( 1 , 4 - h e x a d i e n e ) . The TAH has been used three times i n humans. In the f i r s t two cases (1969 and 1981) the TAH was used t o maintain l i f e u n t i l a heart t r a n s p l a n t could be made a few days l a t e r . The t h i r d case, Dr. Barney C l a r k , i n v o l v e d the permanent replacement of the 9


1.

GEBELEIN


Organs

1

human heart w i t h t h e TAH, and t h e device kept him a l i v e f o r about three a d d i t i o n a l months. (Death was due t o other causes r a t h e r than f a i l u r e o f t h e TAH.) I t i s h i g h l y l i k e l y t h a t t h i s , o r s i m i l a r d e v i c e s , w i l l be used many times i n t h e f u t u r e ( l , 11,


U5-U7).

The most w i d e l y used heart a s s i s t d e v i c e , other than t h e h e a r t - l u n g machine r o u t i n e l y used i n surgery, i s t h e i n t r a a o r t i c b a l l o o n pump (IABP) which c o n s i s t s o f a PEUU b a l l o o n mounted on a hollow c a t h e t e r . The IABP i s i n s e r t e d i n t o t h e a o r t a v i a t h e femoral a r t e r y and i s then expanded and c o n t r a c t e d by an e x t e r n a l pumping system t o match t h e heart beat. While t h i s device does provide s i g n i f i c a n t improvement i n c i r c u l a t i o n and a l s o allows the heart t o r e s t p a r t i a l l y a f t e r a myocardial i n f a r c t i o n , t h e m o r t a l i t y r a t e i s s t i l l 65"90% ( 4 8 ) . Over 40,000 people i n t h e United S t a t e s , and over 100,000 people worldwide, were maintained on d i a l y s i s u n i t s i n 1982 ( l ) . In a d d i t i o n , many others were placed on t h i s d e v i c e , which i s commonly c a l l e d an a r t i f i c i a l kidney, f o r b r i e f periods o f time i n order t o c o r r e c t a temporary problem. The a r t i f i c i a l kidney i s an e x t r a c o r p o r e a l device which c o n s i s t s o f a d i a l y s i s membrane u n i t and various t u b i n g , pumping and r e g u l a t i n g equipment, which i s used t o remove t h e waste m a t e r i a l s from t h e blood and thereby mimics t h e o p e r a t i o n o f a h e a l t h y kidney. The p r e f e r r e d t r e a t ment f o r a d e f e c t i v e kidney i s a c t u a l l y t r a n s p l a n t a t i o n , which was f i r s t done i n 1954. Although a person can f u n c t i o n s a t i s f a c t o r i l y w i t h only one kidney, a t r a n s p l a n t e d organ w i l l be r e j e c t e d by t h e r e c i p i e n t unless c a r e f u l t i s s u e matching i s done. While t h e newer immunosuppressant drugs, such as c y c l o s p o r i n , have aided g r e a t l y i n p e r m i t t i n g greater success i n organ t r a n s p l a n t a t i o n , t h e number o f a v a i l a b l e organs remains w e l l below t h e demand. For t h i s reason alone, many p a t i e n t s remain on d i a l y s i s f o r many years. I n recent y e a r s , p o r t a b l e or wearable devices have been developed which a l l o w t h e p a t i e n t c o n s i d e r a b l e m o b i l i t y compared w i t h t h e past but t h e d i a l y s i s device leaves much t o be d e s i r e d as an i d e a l replacement f o r t h e kidney. U n f o r t u n a t e l y , i t appears u n l i k e l y t h a t a s a t i s f a c t o r y , implantable 'true' a r t i f i c i a l kidney w i l l be developed i n t h e near f u t u r e . The present devices u t i l i z e polymers i n t h e t u b i n g ( u s u a l l y s i l i c o n e rubber, p o l y ( v i n y l c h l o r i d e ) or p o l y e t h y l e n e ; t h e t u b i n g i s e i t h e r t r e a t e d w i t h heparin o r heparin i s added t o t h e blood d u r i n g use t o prevent c l o t t i n g ) and i n t h e membrane i t s e l f ( u s u a l l y c e l l u l o s i c although p o l y a c r y l o n i t r i l e has been used i n the hollow f i b e r type) ( l , 9, 11, I T ) . The pancreas serves s e v e r a l f u n c t i o n s which i n c l u d e s t h e s e c r e t i o n o f t h e enzyme i n s u l i n which c o n t r o l s blood glucose metabolism l e v e l . Over a m i l l i o n d i a b e t i c persons must take i n s u l i n i n j e c t i o n s on a r e g u l a r b a s i s ( l ) . The metabolism cont r o l by t h i s method i s e r r a t i c and s e v e r a l r e s e a r c h groups have been experimenting w i t h polymeric i n f u s i o n pumps i n order t o c o n t r o l the i n s u l i n l e v e l (and thus t h e glucose l e v e l ) more



8

POLYMERIC MATERIALS AND ARTIFICIAL ORGANS

c l o s e l y . I f such a device would be coupled w i t h an implanted glucose sensor, the extent o f c o n t r o l could approach t h a t o f a h e a l t h y pancreas, except f o r i n s u l i n s y n t h e s i s ( l , 4 9 ) . No implantable, a r t i f i c i a l lungs e x i s t a t t h i s time but some research has been done on polymeric membranes t h a t could be used i n such a device. E x t r a c o r p o r e a l blood oxygenators a r e , however, used i n excess o f 100,000 times a year ( l ) and c o n t a i n a t h i n , polymeric membrane t h r u which O2 and CO2 are exchanged. These oxygenators, which e x i s t i n s e v e r a l d i f f e r e n t s t y l e s are w i d e l y used i n by-pass and other operations. The main polymers used are s i l i c o n e rubber but p o l y ( a l k y l s u l f o n e s ) and some others show promise ( l , 50, 5 l ) . The l i v e r i s the main d e t o x i f i c a t i o n organ i n the body and t h e r e f o r e comes i n t o contact w i t h n e a r l y every poison and t o x i n t h a t enters the body. These m a t e r i a l s could occur i n case o f p o i s o n i n g , drug overdose, acute h e p a t i t i s , and a l l e r g i e s . While no t r u e a r t i f i c i a l l i v e r has been developed, and t r a n s p l a n t a t i o n i s r a r e and d i f f i c u l t , s e v e r a l approaches have been attempted t o r e p l a c e and/or a s s i s t the f u n c t i o n o f the l i v e r . The most common method i s hemoperfusion i n which the blood i s passed through a column or bed o f some sorbent m a t e r i a l which can remove the poisons. The sorbents t h a t have been used i n c l u d e c h a r c o a l , ion-exchange r e s i n s , a f f i n i t y chromatography r e s i n s , immobilized enzymes and hepatic m a t e r i a l or pieces o f l i v e r enclosed i n ' a r t i f i c i a l c e l l s ' (9, 52). Various types o f p l a s t i c t u b i n g have been used t o r e p l a c e s e c t i o n s of the g a s t r o - i n t e s t i n a l t r a c t or other t u b e - l i k e p a r t s of the body. These seldom have any f u n c t i o n other than connecting one p a r t of the body w i t h the other. Because of the complex v a r i e t y o f chemical operations i n v o l v e d , i t i s u n l i k e l y t h a t a t r u e a r t i f i c i a l GI t r a c t w i l l be developed i n the near f u t u r e (1,15).

Type (IV) - Sensory Organs Polymeric m a t e r i a l s have been used t o r e p l a c e the e x t e r n a l p a r t of the ear ( u s u a l l y s i l i c o n e s ) and a l s o t o r e p l a c e the o s s i c l e s (PTFE, p o l y e t h y l e n e , s i l i c o n e s ) as w e l l as s e r v i n g as drainage tubes f o r the ear ( l l ) . In a d d i t i o n some research has been done i n which e l e c t r o d e s are implanted i n t o the cochlea and are connected t o an e x t e r n a l microphone. Such devices have been able t o r e s t o r e a s i g n i f i c a n t amount o f hearing t o deaf people. P l a s t i c s are used i n these p r i m a r i l y as coatings f o r the wires and e l e c t r o n i c parts ( l 4 , 53, 5 4 ) . The most common use o f polymeric m a t e r i a l s i n the eye i s i n contact lenses which are worn by s e v e r a l m i l l i o n people. Most s o f t contact lenses are hydrogels made from homo- or copolymers of hydroxyethyl methacrylate; hard contacts are u s u a l l y made from p o l y (methyl methacrylate). I n t r a o c u l a r lenses are put i n t o about 600,000 people a n n u a l l y ( 5 ) . These are u s u a l l y made from p o l y



1.

GEBELEIN


Organs

9

(methyl methacrylate) although hydrogels are being explored f o r t h i s use (55). Some research i s a l s o being done t o enable a b l i n d person t o have some ' s i g h t ' by d i r e c t s t i m u l a t i o n o f t h e v i s u a l area o f the b r a i n w i t h electrodes connected t o a TV type camera. At t h e present, t h i s i s l i m i t e d t o t h e c r e a t i o n o f s m a l l points o f l i g h t ( l 4 , 53, 56). L i t t l e , i f any, research i s being conducted on the senses o f s m e l l , touch or t a s t e t h a t involves polymers. In c o n c l u s i o n , we note that many types o f a r t i f i c i a l organs have been developed u s i n g a v a r i e t y o f polymeric m a t e r i a l s but a l l these devices a r e g e n e r a l l y l e s s s a t i s f a c t o r y than t h e o r i g i n a l , healthy organ. I n most cases, however, t h e a r t i f i c i a l organ functions s i g n i f i c a n t l y b e t t e r than the d e f e c t i v e organ i t r e p l a c e s . Much more research i s needed i n t h i s area. The u l t i m a t e s o l u t i o n w i l l i n v o l v e t h e c r e a t i o n o f newer polymers and a l s o b e t t e r a r t i f i c i a l organ designs.

Literature Cited 1. Gebelein, C.G., "Prosthetic and Biomedical Devices," in Kirk-Othmer Encyclopedia of Chemical Technology, 3rd ed., 1982; 19, 275-313. 2. Gebelein, C.G.; Koblitz, F.F., eds., "Biomedical and Dental Applications of Polymers," Plenum Publ. Corp., New York, 1981. 3. Carraher, C.E.; Gebelein, C.G., eds., "Biological Activities of Polymers," American Chemical Society Symposium Series No. 186, Washington, D.C., 1982. 4. Black, J., "Biological Performance of Materials. Fundamen tals of Biocompatibility," Marcel Dekker, New York, 1981. 5. Hench, L.L., J. Biomed. Mater. Res., 1980; 14, 803. 6. Gebelein, C.G., Org. Coatings Plast. Chem., 1980, 42, 70. 7. Habel, M.B., Biomater. Med. Devices, Artificial Organs, 1979; 7(2), 229. 8. Park, J.B., "Biomaterials, An Introduction," Plenum Publ. Corp., New York, 1979. 9. Chang, T.M.S., "Artificial Kidney, Artificial Liver and Artificial Cells," Plenum Publ. Corp., New York, 1978. 10. White, R.L.; Meindl, J.D., Science, March, 1977; 195, 1119. 11. Kolff, W.J., Artificial Organs, 1977; 1 (1), 8. 12. Andrade, J., ed., "Hydrogels for Medical and Related Applications," American Chemical Society Symposium No. 31, Washington, D.C., 1976. 13. Gregor, H.P., ed., "Biomedical Applications of Polymers," Plenum Publ. Corp., New York, 1975. 14. Kronenthal, R.L.; Oser, Ζ.; Martin, Ε., "Polymers in Medicine and Surgery," Plenum Publ. Corp., New York, 1975. 15. Lee, H.; Neville, Κ., "Handbook of Biomedical Plastics," Pasadena Technology Press, Pasadena, CA, 1971.



10

POLYMERIC MATERIALS AND ARTIFICIAL ORGANS

16. Bement, Jr., A.L., ed., "Biomaterials," U. Washington Press, Seattle, 1971. 17. Gutcho, M., "Artificial Kidney Systems," Noyes Data Corp., Park Ridge, NJ, 1970. 18. Seltzer, R.J., C&EN, Nov. 15, 1982, pp. 61-63. 19. Charnley, J., Plastics & Rubber, 1976; 1, (2), 59. 20. Sonstefard, D.A.; Matthews, L.S.; Kaufer, Η., Sci. Am., 1978; 238 (1), 44. 21. Tohen Ζ., Α., "Manual of Mechanical Orthopaedics," Milam, R.W.; Lopez, E., translators, Charles C. Thomas, Spring field, IL, 1973. 22. Reswick, J.B.; Vodovnik, L. in "Future Goals of Engineering in Biology and Medicine," Dickson, III, J.F.; Brown, J.H.V., eds., Academic Press, New York, 1969, pp. 147-166. 23. Ducheyne, P. and Hastings, G.W., eds., "Fuctional Behavior Of Orthopedic Biomaterials", Vol. I and II, CRC Press, Boca Raton, FL, 1983. 24. Murphy, E.F., J. Biomed. Mater. Res. Symp., 1973; 4, 275. 25. Murdoch, G.; Hughes, J. in "Perspectives in Biomedical Engineering," Kenedi, R.M., ed., MacMillan Press Ltd., London, 1973, pp. 67-72. 26. Scott, R.N. in "Advances in Biomedical Engineering and Medical Physics," vol. 2, Levine, S.N., ed., Wiley-Interscience, New York, 1968, pp. 45-72. 27. Dagalakis, N.; Flink, J.; Stasikelis, P.; Burke, J.F.; Yannis, I.V., J. Biomed. Mater. Res., 1980; 14, 511. 28. Wang, P.Y.; Samji, N.A. in Ref. (2), pp. 29-37. 29. May, P.D. in Ref. (12), pp. 257-268. 30. Chvapil, M., J. Biomed. Mater. Res., 1977; 11, 721. 31. Braley, S.A. in Ref. (12), pp. 277-283. 32. Johnsson-Hegyeli, R. in Ref. (12), pp. 207-233. 33. Braley, S. in "Biomaterials," Stark, L . ; Agarwal, G., eds., Plenum Publ., New York, 1969, pp. 67-89. 34. Myers, G.H.; Parsonnet, V., "Engineering in the Heart and Blood Vessels," Wiley-Interscience, New York, 1969, Chapt. 2-7. 35. Myers, G.H.; Parsonnet, V. in "Cardiac Engineering, Vol. 3 of Advances in Biomedical Engineering and Medical Physics," Nose, Y.; Levine, S.N., eds., Wiley-Interscience, New York, 1970, pp. 335-368. 36. Silver, M.D.; Datta, B.N.; Bowes, V.F., Arch. Pathol., March, 1975; 99, 132. 37. Lefrak, E.A.; Starr, Α., "Cardiac Valve Prostheses," Appleton-Century-Crofts, New York, 1979. 38. Harasaki, H.; Snow, J.; Cloesmeyer, R.; Nose, Y., Inter. J. Artificial Organs, 1979; 2 (2), 73. 39. Bricker, D.L.; Beall, Jr., A.C.; DeBakey, M.E., Chest, 1970; 58, 566. 40. Vaughan, C.D.; Mattox, K.L.; Feliciano, D.V.; Beall, Jr., A.C.; DeBakey, M.E., J. Trauma, 1979; 19, 403.



1.

GEBELEIN


Organs

11

41. Raithel, D.; Groitl, H. World J. Surgery, 1980; 4, 223. 42. Knutson, K.; Lyman, D.J. in Ref. (2), pp. 173-188. 43. Lyman, D.J.; Seifert, K.B.; Knowlton, H.; Albo, Jr., D., in Ref. (2), pp. 163-171. 44. Murabayashi, S.; Nose, Y. in Ref. (2), pp. 111-118. 45. Akutsu, T.; Yamamoto, N.; Serrato, M.A.; Denning, J.; Drummond, M.A. in Ref. (2), pp. 119-142. 46. Eskin, S.G.; Navarro, L.T.; Sybers, H.B.; O'Bannon, W.; DeBakey, M.E. in Ref. (2), pp. 43-161. 47. Pierce, W.S.; Brighton, J.A.; Donachy, J.H.; Landis, D.L.; Rosenberg, G.; Prophet, G.A.; White, W.J.; Waldhausen, J.A.; Arch. Surg. Chicago, 1970; 112, 1430. 48. Bregman, D.; Nichols, A.B.; Weiss, M.B.; Powers, E.R.; Martin, E.C.; Casarella, W.J., Am. J. Cardiol., 1980; 46, 261. 49. Santiago, J.V.; Clemens, A.H.; Clarke, W.L.; Kipnis, D.M., Diabetes, 1979; 28 (1), 71. 50. Gray, D.N. in Ref. (2), pp. 21-27. 51. Zapol, W.M.; Ketteringham, J. in Ref. (10), pp. 287-312. 52. Kulbe, K.D., Artificial Organs, 1979; 3, 143. 53. Kolff, W. in Ref. (10), pp. 1-28. 54. Kinney, S.E., Artificial Organs, 1979; 3, 379. 55. Langston, R.H.S., Artificial Organs, 1978; 2 (1), 55. 56. Sperling, T.D.; Bering, E.A.; Pollack, S.V.; Vaughan, H.G., eds., "Visual Prosthesis, The Interdisciplinary Dialogue," Academic Press, New York, 1971. RECEIVED April 23, 1984


The Basics of Artificial Organs - American Chemical Society

Recommend Documents