Polymer Biomaterials

There are a large number of uses for polymers in the biomaterials field. These arise due to the wide variety of properties possible.

OBJECTIVES

 to introduce some fundamental polymer properties and the factors that influence them  to provide an overview of the uses of polymers as biomaterials 1

POLYMERS

Polymers - long chain molecules of high molecular weight -(CH 2 ) n n State Use 1-4 gas burned for energy 5-11 9-16 16-25 25-50 1000 3000 liquid med. visc.

liquid gasoline kerosene hi visc. liq.

solid oil, grease paraffin wax tough plastic PE bottles, containers 2

Common Polymer Biomaterials

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Polymers In Specific Applications

application properties and design requirements polymers used

dental ophthalmic orthopedic cardiovascular drug delivery sutures •stability and corrosion resistance, plasticity •strength and fatigue resistance, coating activity •good adhesion/integration with tissue •low allergenicity •gel or film forming ability, hydrophilicity •oxygen permeability •strength and resistance to mechanical restraints and fatigue •good integration with bones and muscles •fatigue resistance, lubricity, sterilizability •lack of thrombus, emboli formation •lack of chronic inflammatory response •appropriate drug release profile •compatibility with drug, biodegradability •good tensile strength, strength retention •flexibility, knot retention, low tissue drag PMMA-based resins for fillings/prosthesis polyamides poly(Zn acrylates) polyacrylamide gels PHEMA and copolymers PE, PMMA PL, PG, PLG silicones, Teflon, poly(urethanes), PEO PLG, EVA, silicones, HEMA, PCPP-SA silk, catgut, PLG, PTMC-G PP, nylon,PB-TE 4

Properties: Molecular weight

synthetic polymers possess a molecular weight distribution N i M i M w = å i N i M i 2 å i N i M i M n = å i å N i M i N i i dispersity index = M w /M n 5

The Bulk State : Solid

Polymers can be either amorphous or semi-crystalline, or can exist in a glassy state.

amorphous glassy state   hard, brittle no melting point semi-crystalline glassy state    hard, brittle crystal formation when cooled exhibit a melting point Glass transition temperature (Tg) 6

Thermal Behavior

semi-crystalline T 10 Liquid Viscous Liquid Rubber T m tough plastic T g semi-crystalline plastic crystalline solid 1000 100000 molecular weight (g/mol) 1000000 7

Crosslinked Networks

crosslinks  covalent; H-bonding; entanglements crosslinking   increased molecular weight swell in solvents • organogel • hydrogel 8

Thermal Properties

Polymer Nylon 6,6 UHMWPE Silicone poly(urethane) poly(methylmethacrylate) poly(D,L-lactide) poly(  -caprolactone) poly(glycolic acid) T g (ºC) 45 -125 -123 0-90 105 50 - 60 35 T m (ºC) 267 140 -29 125-225 160 amorphous 57 210 9

Viscoelasticity

The response of polymeric materials to an imposed stress may under certain conditions resemble the behavior of a solid or a liquid.

Strain 10

Mechanical Properties

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Diffusion in Polymers

Polymers can also act as solvents for low molecular weight compounds. The diffusion of small molecular weight components in polymers is important in a number of fields :      purification of gases by membrane separation dialysis prevention of moisture loss in food and drugs (packaging) controlled drug delivery (transdermal patches, Ocusert) polymer degradation 12

Diffusion in Polymers

Flux is dependent on :   solubility of component in polymer diffusivity of component in polymer These in turn depend on :     nature of polymer temperature nature of component interaction of component with polymer 13

Solubility Estimation

From Hildebrand, the interaction parameter, c , is defined as : c = V 1 ( d 1 - d 2 ) 2 RT The solubility parameter, d , reflects the cohesive energy density of a While a precise prediction of solubility requires an exact knowledge of the Gibbs energy of mixing, solubility parameters are frequently used as a rough estimator.

In general, a polymer will dissolve a given solute if the absolute value of the difference in d between the materials is less than 1 (cal/cm 3 ) 1/2 .

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Diffusivity

experimental observations  effect of T vs T g 15

Diffusivity

effect of permeant size 16

Diffusivity : Effect of Crystallinity

solutes  do not penetrate crystals readily  take path of least resistance • through amorphous regions  increased path length D 1,c = D 1,a æ è 1 - f 1 + f c c x ö ø D 1,c D 1,a = diffusivity in semi-crystalline polymer = diffusivity in amorphous polymer f c = volume fraction of crystals x = shape factor (=2 for spheres) (Mathematics of Diffusion) 17

Example of Undesirable Absorption

 poppet-style heart valve • poppet is composed of PDMS • in small % of patients the poppet jammed or escaped • recovered poppets were yellow, smelled, and had strut grooves 18

Leaching - Undesirable

 polymers often contain contaminants as a result of their synthesis/manufacturing procedure/equipment  may also contain plasticizers, antioxidants and so on  these contaminants are a frequent cause of a polymer ’ s observed incompatibility 19

Drug Delivery

Ocusert TD - Scopolamine 20

In Vivo Degradation of Polymers

 no polymer is impervious to chemical and physical actions of the body Mechanisms causing degradation

Physical Chemical sorption/swelling hydrolysis softening oxidation dissolution enzymatic stress cracking fatigue cracking

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Hydrolytic Degradation

hydrolysis  the scission of chemical functional groups by reaction with water there are a variety of hydrolyzable polymeric materials: esters amides anhydrides carbonates urethanes 22

Hydrolytic Degradation

degradation rate dependent on  hydrophobicity         crystallinity T g impurities initial molecular weight, polydispersity degree of crosslinking manufacturing procedure geometry site of implantation 23

Hydrolytic Degradation

bulk erosion

 (homogeneous) uniform degradation throughout polymer process  random hydrolytic cleavage (auto-catalytic)  diffusion of oligomers and fragmentation of device

surface erosion

 (heterogeneous) polymer degrades only at polymer-water interface 24

Polyesters

Polyesters

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Oxidative Degradation

usually involves the abstraction of an H to yield an ion or a radical  direct oxidation by host and/or device • release of superoxide anion and hydrogen peroxide by neutrophils and macrophages • catalyzed by presence of metal ions from corrosion 27

Poly(Carbonates)

PEC in vivo M. Acemoglu, In. J. Pharm.

277 (2004) 133-139 28

Enzymatic Degradation

Natural polymers degrade primarily via enzyme action  collagen by collagenases, lysozyme  glycosaminoglycans by hyaluronidase, lysozyme There is also evidence that degradation of synthetic polymers is due to or enhanced by enzymes.

C.G. Pitt et al., J. Control. Rel. 1(1984) 3-14 Z Gan et al., Polymer 40 (1999) 2859 29