1 MASE 542/CHEM 442 BIOMATERIALSSpring 2006 H. Funda Yagci Acar

2 Polymeric biomaterials

3 Synthetic polymeric biomaterialsHydrophobic/ non-water-absorbing materials more polar materials Water swelling water-soluble Biodegradable or stable ! silicone rubber (SR), polyethylene (PE), polypropylene (PP), poly(ethylene terephthalate) (PET), polytetrafluoroethylene (PTFE), and poly(methyl methacrylate) (PMMA) poly(vinyl chloride) (PVC), copoly(lactic–glycolic acid) (PLGA), and nylons, poly(hydroxyethyl methacrylate) (PHEMA) poly(ethylene glycol) (PEG or PEO).

4 Sterilization reduce the chances of clinical infectionsteam, dry heat, chemicals, and irradiation. heat or ionizing radiation may affect the properties of the polymer, by chain scission or creating cross-links. Chemical agents such as ethylene oxide may also be absorbed by a material and later could be released into the body. Therefore, devices sterilized with ethylene oxide require a period of time following sterilization for any residues to be released before use.

5 HIPS SBS Poly(styrene-butadiene-styrene): hard rubberused for things like the soles of shoes, tire treads, and other places where durability is important

6 PMMA Amorphous Thansparent High refractive index Hard plastic ThoughProcessable Stable Biocompatable Free radical polymerization by heat or UV light source Commercial names: Lucite, Plexiglass Intraocular lenses, soft contact lenses, bone cement

7 PHEMA Poly(hydroxyethyl methacrylate)Thansparent High refractive index Hydrophilic Hydrogel: slightly crosslineked with EGDMA To retain dimentional stability Biocompatable Inert, nondegradable Heat sterilization Processable (various shapes and forms) Free radical polymerization by heat or UV light source soft contact lenses

8 Polyacrylic acid Hydrophilic Physical crosslinking of an ionomerHydrogel if crosslinked Dental cements Drug delivery Muchosal adhesives

9 Polyethylene good toughness wear resistanceresistant to lipid absorption high-density PE: tubing for drains and catheters low-density material cannot withstand sterilization temp Radiation sterilization in an inert atmosphere may also provide some covalent cross-linking that strengthens the PE ultrahigh-MW form: acetabular component in artificial hips and other prosthetic joints

10 PTFE Teflon very high melting polymer (Tm = 327◦C) very hydrophobicexcellent lubricity catheters. In microporous form, known generically as e-PTFE (Gore-Tex) vascular grafts. low friction: the acetabular component of the first hip joint prosthesis, but it failed because of its low wear resistance and the resultant inflammation caused by the PTFE wear particles. DOI: / X.73578

11 high resistance in vivo degradation low thrombogenicity For Teflon compatible as synthetic vascular graft, it must have certain charecteristics. high resistance in vivo degradation low thrombogenicity  exceptional physical and mechanical properties relative high yield and breaking points, resist high tension torsion and stresses fabricated to such extent that it has high elastic capacities able to compress and decompress by muscular tissue and ligaments in action Characteristics approved by FDA for Teflon vascular graft: sizes smaller than 6mm for arterial use and 6mm or larger for veins having outer coating made of biological substance such as albumin or collagen like silicone thinner wall, this is to create a softer and better handling graft stretchable wall, also for less bleeding and better handling. external support and function to resist compression and kinking. / Read more:

12 PVC hard, brittle With plasticizers, it can be made flexiblesoftubing and blood storage bags Typical tubing uses include blood transfusion, feeding, and dialysis. problems for long-term applications plasticizers can be extracted by the body. While these plasticizers have low toxicities, their loss also makes the PVC less flexible.

13 Poly(dimethyl siloxane) (PDMS)biocompatible elastomers extremely versatile low intermolecular interactions in silicones very low Tg (146 K) Properties are less temperature sensitive than other rubbers high free volume high solubility and high diffusion coefficient of gas into silicones limited by its relatively poor mechanical strength. Sometimes modified with aromatic rings that can toughen it low surface tension capable of wetting most surfaces promotes good film formation and good surface covering. very hydrophobic films good release properties although porous polypropylene or polysulfone polymers have recently become more used as oxygenator membranes

14 PET one of the highest volume polymeric biomaterialshigh-melting (Tm =267◦C) crystalline polymer very high tensile strength knit, velour, or woven fabrics and fabric tubes, and also as nonwoven felts. Dacron: woven arterial grafts. PET fabrics: fixation of implants and hernia repair. PET : ligament reconstruction, reinforcing fabric for tissue reconstruction with soft polymers such as SR.

15 PEG highly hydrated state on the surfacesexhibit steric repulsion based on an osmotic or entropic mechanism. This phenomenon contributes to the protein- and cell-resistant properties of surfaces containing PEGs hide from immune recognition in drug delivery as conjugates with low solubility drugs, immunogenic or fairly unstable protein drugs enhance the circulation times, escape from liver and increase stabilities of the drugs. It is also used as PEG–phospholipid conjugates to enhance the stability and circulation time immobilized on polymeric biomaterial surfaces to make them “nonfouling.”

16 Int. J. Mol. Sci. 2011, 12, 4872-4884; doi:10.3390/ijms12084872Molecular structure of PLL-g-PEG (J. Hubbell, D. Elbert, Chem Biol 5: (3) (1998))

17 Biodegradable PolymersPLGA is a random copolymer resorbable surgical sutures, drug delivery systems, and orthopedic appliances such as fixation devices. degradation products are endogenous compounds (lactic and glycolic acids) and nontoxic The presence of ester linkages in the polymer backbone allows gradual hydrolytic degradation (resorption). The rate of degradation can be controlled by the ratio of polyglycolic acid to polylactic acid

18 HYDROGELS Water-swollen, crosslinked polymeric structuresAbsorbs from 10% to thousands of times of their dry weight in water Crosslinking: Covalent Physical Molecular entanglement or secondary forces H-bonding, ionic interactions, hydrophobic interactions, crystallites

19 HYDROGELS Based on preparation: Homopolymer gels Copolymer gelsInterpenetrating gels (first polymer swollen with the second monomer and polymerized) Based on ionic character Neutral Anionic Cationic Ampholytic

20 HYDROGELS Based on physical structure: Amorphous (chain entanglement)Semicrystalline (dense regions of ordered structure) H-bonded or complexation STRUCTURES ARE NEVER PERFECT! INHOMOGENEITIES ALWAYS EXIST! NOT ELASTIC ENOUGH-CAN BREAK!

21 HYDROGELS Method of Preparation: Chemical Crosslinlingsmall crosslinking agents (at least difunctional) Copolymerization with multifunctional monomer Monomer + linear polymer + crosslinling agent Chemical crosslinking can be achieved by radical methods utilizing: UV Gamma Rays

22 Biomedical hydrogels Highly swollen hydrogels: PVA, PNVP, PEG ModeratePHEMA

23 At equilibrium Elastic retractive force of the polymer chainCompatability of the water and the polymer (mixing) EQUILUBRIUM SWELLING LEVEL chemical potential of water in and out is equal

24 HYDROGEL SWELLING Function of q= weight of dry polymer ChemistryCrosslink density Temperature Swelling agent Polymer volume fraction V = Volume of dry polymer Volume of swollen gel Volume degree of swelling q= weight of dry polymer weight of swollen gel Weight degree of swelling Swelling degree

25 DEGREE OF SWELLING impacts…Solute diffusion through the gel Surface properties and mobility Optical properties (contact lenses!) Mechanical properties

26 Biomedical ApplicationsCOMPOSITION+ swelling degree + mechanical properties Blood-compatable Non-ionic PVA, PHEMA, PNVP,PEO Contact lenses Mechanical stability Refractive index Oxygen permeability Drug delivery Controlled release Blood circulation time Kidney membranes Artifical skin Tissue engineering Wound healing membranes

27 Physical Forms Solid molded (like contact lense)Pressed powder ( pills for orak uptake) Microparticles ( wound treatment) Coating (on implants) Membranes ( transdermal delivery) Liquids (form gels upon heating or cooling)

28 PHEMA Non-degrading Permeable to metabolites Processable SterilizableDry (Zerogel) form; polymer is glassy (like PMMA) Tg ~ 100°C Hydrated form (Gel); water plasticises the polymer Tg << Room temperature The HEMA contact lens is therefore a SOFT (flexible) lens

29 Drug release Swollen state is rubbery Poly(HEMA-co-MAA)Rate depends on: Water diffusion inside the gel Drug diffusion out of gel No initial burst of drug Inorder for drug to leave, water needs to come in first

30 RESPONSIVE HYDROGELS INTELLIGENT/SMARTResponsive to environmental or physiological changes Response is REVERSIBLE Stimulus: pH, Temp, ionic strength, enzymatic reaction, electrical, magnetic As Carriers As self-regulated drug delivery systems

31 Smart Polymers as Biomaterials

32 pH Responsive HydrogelsIonic pendant groups are necessary : ACIDIC OR BASIC PENDANT GROUP Swelling forces are more powerfull compared to non-ionic gels Mesh size changes as a function of pH Example: PAA, PAAm, P(HEMA-co-MAA)

33 Temperature Responsive GelsLCST: Lower Critical Solution Temperature Below Tc : Polymer is soluble- swollen Above Tc : Polymer is hydrophobic-collapsed Example: PNIPAAm (Poly(N-isopropyl acrylamide)) LCST= 34.3° C LCST can ve increased by copolymerization with ionic monomer Macromolecules 2001, 34,

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35 Self assembled structuresBlock copolymers (triblock generally) Pluronics

36 Complexing Hydrogels Non-covalent Based on affinity of polymersIntermolcular or intramolecular H-bonding, electrolyte complex, stereocomplex Stability depends on: Temp Ionic strength pH Network composition and structure Length of interecting polymer chains Physical gel As crosslinking increase: mesh size and degree of swelling decrease

37 Complex hydrogels PMAA-g-PEG pH responsive H-bonded (crosslinking)

38 Biomed. Mater. 4 (2009)

39 Biomed. Mater. 4 (2009)

40 Biomed. Mater. 4 (2009)

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