1. 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

2. POLYMERS • Polymers - long chain molecules of high molecular weight • -(CH2)n-

3. Common Polymer Biomaterials

4. Polymers In Specific Applications

5. Ni Mi Properties: Molecular weight • synthetic polymers possess a molecular weight distribution polydispersity index = Mw/Mn

6. 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

7. Glass transition temperature, Tg • related to chain mobility • increased flexibility, lower Tg • factors : • flexible links in backbone • size of pendent groups • interaction between chains • plasticizers interfere with bonding, increase chain movement, decrease Tg

8. Tg • effect of Molecular weight • Fox-Flory eqn. • K = constant for given polymer • Tg∞ = Tg for infinite M • for copolymers (Fox-Flory) • w = weight fraction of monomer in copolymer

9. Effect of Temperature on Polymer Properties • amorphous viscous liquid rubbery Tg T glassy Mw

10. Effect of Temperature • semi-crystalline Rubber Liquid Viscous Liquid Tm tough plastic T Tg semi-crystalline plastic crystalline solid 10 1000 100000 1000000 molecular weight (g/mol)

11. Crosslinked Networks • crosslinks • covalent; H-bonding; entanglements • crosslinking • increased molecular weight • swell in solvents • organogel • hydrogel

12. Thermal Properties

13. Temperature Effects Tg Tm semicrystalline log(Modulus) crosslinked T linear amorphous Temperature

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

15. Mechanical Properties

16. 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

17. 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

18. Solubility Estimation • From Hildebrand, the interaction parameter, c, is defined as : • The solubility parameter, d, reflects the cohesive energy density of a material, or the energy of vapourization per unit volume. • 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/cm3)1/2.

19. Diffusivity • experimental observations • effect of T vs Tg

20. Diffusivity • effect of permeant size

21. Diffusivity : Effect of Crystallinity • solutes • do not penetrate crystals readily • take path of least resistance • through amorphous regions • increased path length D1,c = diffusivity in semi-crystalline polymer D1,a = diffusivity in amorphous polymer fc = volume fraction of crystals x = shape factor (=2 for spheres) (Mathematics of Diffusion)

22. 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

23. 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

24. Drug Delivery Ocusert TD - Scopolamine

25. In Vivo Degradation of Polymers • no polymer is impervious to chemical and physical actions of the body Mechanisms causing degradation

26. 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

27. Hydrolytic Degradation • degradation rate dependent on • hydrophobicity • crystallinity • Tg • impurities • initial molecular weight, polydispersity • degree of crosslinking • manufacturing procedure • geometry • site of implantation

28. 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

29. Polyesters

30. Polyesters fractional change in molecular weight

31. 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

32. Poly(Carbonates) PEC in vivo M. Acemoglu, In. J. Pharm. 277 (2004) 133-139

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