17 September 2010

BIOMEDICAL APPLICATIONS OF SYNTHETIC POLYMERS



INTRODUCTION


The widespread use of synthetic polymers in technology and in every day life is an accepted feature of modern civilization .There exists one important area in which the use of synthetic polymers has generally been cautious and limited , that is field of medicine has become one of the principal challenges facing the polymer scientists .The types of synthetic polymers needed for biodmedical applications can be grouped roughly into three categories . Polymers that are sufficiently biostable to allow their long-term use in artificial organs ie , In Blood Pumps , Blood Vessel Prosthesis , Heart Valves , Skeletal Joints , Kidney Prosthesis and so on . Polymers that are bioerodable-materials that will serve a short-term purpose in the body and decompose to small molecules that can be metabolized or excreted , sometimes with the concurrent release of drug molecules . Polymers that are water soluble and that form part of plasma or whole blood substitute solutions or which function as macromolecular drugs . A polymer must fulfill certain critical requirements if it is to be used in an artificial organ .It must be physiologically inert , the polymer itself should be stable , it must be strong and resistant to impact , it should be chemically and thermally stable.

CARDIOVASCULAR APPLICATIONS


HEART VALVES & VASCULAR PROSTHESIS:

Polymers have been used extensively to correct cardiovascular disorders . Defective heart valves can be replaced by mechanical valves based on various designs .In one design, a ball of silicone rubber is retained inside a stainless steel cage.
{Starr-Edwards ball-type heart valves constructed from a silicone rubber ball, a chrome-cobalt cage, and a Teflon ring for suturing to the heart tissue.}

The silicone rubber is used because of it`s inertness, elasticity, and low capacity to cause blood clotting .Valves of this type are still being used .
A more recent design makes use of a small, circular plates as a flap valve,with the flap made from pyrolytic carbon or poly(oxymethylene).

Another surgical practice is to implant modified(cross-linked)tissue heart valves from pigs(“porcine valves”). Devices fabricated from synthetic hydrogels may eventually replace porcine valves.

Aneurisms(balloon-like expansions of the arterial wall )can be repaired by reinforcement of the artery with a tube of woven polyester or PTFE fabric.Completely blocked arterial sections are removed and replaced by a tube of porous PTFE. The polymer is relatively noninteractive with blood from the polymer.


THE ARTIFICIAL HEART:


For patients with irreversibly damaged heart, the functions of the damaged heart may be taken over permanently or temporarily by an artificial pump. Synthetic elastomers and rigid polymers have been used extensively for the conuction of these devices. Unfortunarely, most synthetic polymers accelerate the clotting of blood. Avoidance of the clotting process is depends on
the design of the pump and presence or absence of turbulence as well as on the materials used for construction.



HEART PUMP DESIGNS:


The Auxiliary blood pumps to bypass or supplement the of a damaged heart until it can repair it self. Many of the booster pumps have used a rigid housing, often made of reinforcfed epoxy resin, with an internal tube of silicone rubber


Compressed air applied inside the rigid casing compresses the silicon or PU rubber inner tube which is connected to the aorta and this forces blood from the pump. Valves may be used to prevent back flow, or the compression cycle may be synchronized with the pumping motion of the heart.

A related device is the intraaortic balloon, a 25cm*2cm polyurethane ballooninserted in to the aorta which expands as compressed helium or carbon dioxide is pulsed in or out. Other devices use hemisphere of titanium,polycarbonate,or PMMA containing a PU diaphragm . Pulses of compressed air or carbon dioxide actuate the diaphragm and cause the pumping of the blood.

The total artifical heart pumps that can completely replace the living organ.They resembles the general structure of a human heart by which are actuated by compressed gas or oil.


POLYMERS FOR HEART PUMPS:

A wide variety of polymers such as Silicone rubber, Polyurethane rubber, Dacron polyester, Teflon, Polycarbonate, PMMA, PVC, and Pyrolytic carbon. Most of these material cause blood clotting, destruction of red cells, or alteration of the blood proteins, although some are markedly better than others.

Polyurethanes are among the most commonly used flexible biomaterials. They have excellent flexing strength. The diaphragm in a heart pump would have to withstand about 90 million flexing motions without breaking over a 10 year period. Calcification of PU membranes is a problem during long-term use.

Silicone rubber is an ideal biomaterial. Its chemical inertness is impressive, and it is soft and flexible. However, it can promote blood clotting if the blood is flowing slowly, and it can fail after continuous flexing. Another problem is the tendency of silicone rubber to absorb fats from the blood, to swell, and eventually to weaken. Fluoroalkylsiloxane polymers or polyphosphazenes may prove to be more suitable for artificial heart applications.

The ability of a synthetic polymer to initiate the clotting of blood depends on the nature of the surface (smooth surfaces are better than rough) and on the chemical and physical properties of the polymer. Because the inside lining of blood vessels is negatively charged, it has also been speculated that polymers with a surface charge might be more effective than neutral polymers

.

TISSUE ADHESIVES AND ARTIFICIAL SKIN :



A group of polymers based on the poly(alpha-cyanoacrylate)structure have proved to be effective to glue tissues together. Alpha-cyanoacrylates have the general formula,
Where group R can be methyl, butyl, octyl, and so on. CN
These monomers polymerize by an anionic mechanism |
in the presence of water. Higher alkyl derivatives CH2=C
polymerize more rapidly on biological substrates and |
are less irritating to tissues than are the lower alkyl C=O
derivatives . In addition to their use as skin adhesives, |
they have been tested as adhesives in corneal and O
retinal surgery , and as an adjunct to suturing in |
internal surgery. R


Synthetic poly(amino acid) films are used as synthetic skin to cover large burns.Velours of nylon fiber have also been tested for this use, as have films of poly(alpha-cyanoacrylates).

BONES,JOINTS AND TEETH:


Bone fractures are occasionally repaired with the use of polyurethanes, epoxy resins and rapid-curing vinyl resins. Silicone rubber rods and closed-cell sponges have been used as replacement finger and wrist joints, and vinyl polymers and nylon have been investigated as replacement wrist bones or elbow joints. Further more, cellophane and more recently, silicone rubber have been used in knee joints to prevent fusion of the bones.

In hip-joint surgery with the use of stainless steel or polyethylene ball joints attached to the femur by means of a PMMA filler and binder. Teflon fabric and silicone rubber have been used to make synthetic ligaments and tendons.

Synthetic polymers have been utilized for the fabrication of dentures. PMMA is the principal polymer used both for acrylic teeth and for the base material. Acrylic resins are also used for dental crowns, and epoxy resins are sometimes employed to cement crowns to the tooth post. More recent work and anticipated developments include the use of polymeric coatings or paint to prevent the decay of teeth and the development of thermo or photo-setting polymers to replace silver amalgam or gold as tooth-filling materials.


CONTACT LENSES AND INTRAOCULAR LENSES:



Rigid polymers such as PMMA have traditionally been used for ‘hard’ contact lenses ,the modern tendency is toward flexible or ‘soft’ contact lenses. A soft contact lens is made from a lightly cross linked, water-soluble polymer. Such polymers swell in aqueous media but do not dissolve. Instead they form soft hydrogels , the expanded shape of which is defined at the point of cross linking.
The design of hydrogels for intraocular lenses (ie, for lenses to replace the natural lens following eye injury or removal of catatact-damaged lenses) is a special challenge since the replacement lens must be folded without damage into a small volume before insertion through a small incision into the eye.


ARTIFICIALKIDNEY AND HEMODIALYSIS MATERIALS :

Cellophane (regenerated cellulose) has been used for semi permeable dialysis membranes in conventional kidney machines. For miniaturization of machine bundles of hollow fibers are used as a dialysis cell. In one particular development, a bundle of 2000 to 11,000 hollow fibers of modified PAN (17 cm long and 300micro meter dia:)are used. The polymer is “heparinized” to prevent blood clotting. Hollow rayon fibers or polycarbonate or cellulose acetate fibers have also been used for the same purpose.


OXYGEN-TRANSPORT MEMBRANES:

Surgical work on the heart frequently requires the use of a heart-lung machine to circulate and oxygenate the blood. Many of such machines make use of a membrane through which oxygen and carbon dioxide must pass. Poly(dimethylsiloxane) membranes are highly efficient gas transporters. They are made by dip-coating a Dacron or Teflon screen in a xylene dispersion of silicone rubber. When dried, a film of .075 mm or more in thickens can be obtained, and this can be incorporated into the oxygenator . silicone rubber membranes have also been tested in “artificial gills” for under water breathing.


BIOEODABLE POLYMERS
Three medical applications exists for polymers of this type .

a) SURGICAL SUTURES:

Catgut used for all sutures recently is relatively inert and post operative procedure were usually necessary for the removal of the suture after the normal 15-days healing of the tissue. A replacement for catgut is synthetic poly(glycolic acid) or condensation copolymers of glycolic acid with lactic acid. Poly(glycolic acid) has a high tensil strength and is compatible with human tissue. However, it differs from catgut in being totally absorbable by many parients within 15 days, thus removing the need for a suture-removal operation. The polymer degrades by hydrolysis to nontoxic glycolic acid.

b) TISSUE INGROWTH POLYMERS :

Polymers like polyurethans degrade slowly as they are colonized and replaced by living cells of the host. They are clear advantages to the use of biomaterials of this type, since the long-range biocompatibility problems become less important. Polyanhydrides have the right properties to be utilized in this way. A group of amino acid ester-substituted polyphosphazenes, such as, NHCH2COOC2H5
|
-(N=P)-n
|
NHCH2COOC2H5
Which degrades slowly to amino acid, phosphate, and ethanol, which are metabolized, and traces of ammonia , which are exerted.

c) CONTROLLED RELEASE OF DRUGS:

Three approaches are there to use polymers to effect a slow release of drugs. They are,

(1) Diffusion-controlling Membranes Or Matrices:

Many chemotherapeutic drugs are relatively small molecules that can diffuse slowly through polymer membranes. Thus, if an aqueous solution of a drug is enclosed by a polymer membrane, the drug will escape through the membrane at a rate that can be controlled by membrane thickness and composition. A device that employs this principle is in use for the slow controlled release of the antiglaucoma drug, pilocarpine, from a polymer capsule placed beneath the eyelid.

The same principle applies if a film, rod or bead of a of polymer is impregnated with a drug and it is then implanted in the body at a site where the drug can have the maximum beneficial effect.

One important medical advantage in controlled-release devices of this kind is that the drug delivery system can be removed at any time when the therapy is no longer needed.

(2) Solid Biodegradable Matrices:

An excellent way to achieve the slow, controlled release of a drug from a solid matrix is to use a biodegradable polymer as the matrix. As the polymer degrades slowly (usually by hydrolysis), the chemotherapeutic molecules are released. An important requirement is that the hydrolysis products from the polymer should be nontoxic and readily excreted. A second requirement is that rate of release should follow a predetermined protocol. For example for treatment of some diseases a burst of drug in high local concentration might be followed by no release, with the cycle repeated at precise intervals. Alternatively (and more usually ),a so called “Zero Order” protocol may be preferred in which the rate of release of the drug remains constant over a period of days, weeks or months. These requirements provides many opportunities for ingenuity in both the design of the matrix polymer and shape of the device.

A number of polymers, polyglycolic acid , poly(amino acid ester phosphazenes) such as polyphosphazenes with imidazolyl sugar or glyceryl residues as side groups, and aliphatic polyanhydrides are all of interest for this application.

(3)Water Soluble Polymer Bound Drugs:

Water soluble biodegradable polymers are of interest for two types of applications. First , water soluble polymers that are bound to drug molecules could bring about a marked improvement in the behavior of most pharmaceuticals. Second there is the prospect that such polymers can be used in synthetic blood substitutes as viscosity enhancers or as oxygen transport macromolecules.

Water soluble polymers diffuse only slowly through the tissues and more over, will not be excreted as rapidly as small molecules because macromolecules can not normally pass through semi permeable membranes. Thus a polymer bound drug should offer considerable advantages over a small molecule drug.

Three possibilities exist , (1) The drug could be linked to a relatively stable molecule, in which case the activity of the drug and its entry in to the cell may be modified by the presence of the polymer . (2) If the polymer degrades in the body and concurrently release the drug, the chemotherapeutic activity of the drug will be unchanged. (3) The water soluble polymer itself is bioactive.

It will be clear that the design and synthesis of polymers that have the correct water solubility, lack of toxicity and an appropriate rate of hydrolytic decomposition at body temperature is one of the most demanding challenges faced by the polymer chemists.




POLYMERIC BLOOD SUBSTITUTES:

Synthetic polymers have been investigated for use in plasma substitutes and as volume expanders to reduce the amount of whole blood needed, for example during the use of a heart- lung machine. Furthermore, the transmission of hepatitis and other diseases through the use of pooled plasma provides a continuing incentive for the development of a synthetic substitute for this fluid. Poly(Vinyl Pyrolidone) was used extensively as a colloidal plasma substitute for the treatment of casualties. Its disadvantages for this applications are connected with its poor biodegradability. Hence, there is a serious need for the development of a water soluble polymer that is nontoxic and biodegradable. Some water soluble Poly Phosphazenes may be of value for this application.


 

 

CONCLUSION



The pace of revolutionary discoveries now in synthetic Polymers applied for biomedicine is expected to accelerate in the next decade worldwide. This will have a profound impact on existing materials and emerging technologies. A decade ago the application of synthetic polymers in biomedicine was only a concept with great potential. Today it is a reality and tomorrow it will flourish.




BIBILIOGRAPHY


1) Contemporary Polymer Chemistry-H.R.Allcock & F.W.Lampe.
2) Biologically Active Synthetic Polymers-D.S.Breslow.
3) Polymeric Drugs-H.G.Batz.
4) The Chemistry And Properties Of The Medical-Grade Silicones-S.A.Braley.

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