Hydrogels (2)

8/6/2019 Hydrogels (2)

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HydrogelsHydrogels

Water swollen crosslinked polymersWater swollen crosslinked polymers

Crosslinks may occur:Crosslinks may occur:

by reaction of one or more monomersby reaction of one or more monomers hydrogen bondshydrogen bonds

van der Waals interactionsvan der Waals interactions

Exceptional promises for biomedical useExceptional promises for biomedical use


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HydrogelsHydrogels

Classification based on preparation methodClassification based on preparation method

homopolymer hydrogels (one type of hydrophilic mer)homopolymer hydrogels (one type of hydrophilic mer)

copolymer hydrogels (two types of mers, at least onecopolymer hydrogels (two types of mers, at least one

hydrophilic)hydrophilic) multipolymer hydrogels (more than three types ofmultipolymer hydrogels (more than three types of

mers)mers)

interpenetrating polymeric hydrogels (swelling ainterpenetrating polymeric hydrogels (swelling a

network of polmernetwork of polmer11 in merin mer22, making intermeshing, making intermeshingnetwork of polymernetwork of polymer11 and polymerand polymer22))


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HydrogelsHydrogels

Classification based on ionic chargesClassification based on ionic charges

neutral hydrogelsneutral hydrogels

anionic hydrogelsanionic hydrogels

cationic hydrogelscationic hydrogels

ampholytic hydrogelsampholytic hydrogels

Classification based on structureClassification based on structure

amorphous hydrogels (chains randomly arranged)amorphous hydrogels (chains randomly arranged) semicrystalline hydrogels (dense regions of orderedsemicrystalline hydrogels (dense regions of ordered

macromolecules, i.e. crystallites)macromolecules, i.e. crystallites)

hydrogenhydrogen--bonded hydrogelsbonded hydrogels


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HydrogelsHydrogels

Connection between chains called as crosslinkConnection between chains called as crosslinkor junctionor junctionCrosslinks may be induced duringCrosslinks may be induced duringpolymerization or by radiation followingpolymerization or by radiation followingpolymerizationpolymerizationInterchain connections can be:Interchain connections can be: a carbon atoma carbon atom chemical bridgechemical bridge van der Waalsvan der Waals hydrogen bondshydrogen bonds molecular entanglementsmolecular entanglements


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HydrogelsHydrogels

Crosslink structure:Crosslink structure:A)A) ideal network withideal network with

tetrafunctional covalenttetrafunctional covalentcrosslinks (rarelycrosslinks (rarelyobserved)observed)

B)B) multifunctional junctionsmultifunctional junctions

C)C) molecularmolecularentanglements (couldentanglements (couldbe permanent or semibe permanent or semi--permanent)permanent)

Mc: Molecular weight betweencrosslinks


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HydrogelsHydrogels

Defects in crosslinkDefects in crosslinkstructure:structure:

D) unreacted functionalityD) unreacted functionality

E) chain loopsE) chain loops

Note that neither of theNote that neither of thetwo configurationstwo configurationscontribute to mechanicalcontribute to mechanicalstrength or physicalstrength or physicalproperties of the networkproperties of the network


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Hydrogels: PreparationHydrogels: Preparation

Prepared by swelling crosslinked structures inPrepared by swelling crosslinked structures inwater or in biological fluids containing waterwater or in biological fluids containing waterCrosslinks can be induced by radiation orCrosslinks can be induced by radiation orchemical reactionchemical reaction Radiation reactions include electron beams, gammaRadiation reactions include electron beams, gamma--

rays, Xrays, X--rays, or UV lightrays, or UV light Chemical crosslinkingChemical crosslinking

small molecular weightsmall molecular weight crosslinking agentscrosslinking agents that links twothat links twochains together through its dichains together through its di-- or multifunctional groupsor multifunctional groups

copolymerizationcopolymerization--crosslinkingcrosslinkingreactions between thereactions between themonomers and a multifunctional monomer that is present inmonomers and a multifunctional monomer that is present insmall quantititessmall quantititescombination of abovecombination of above


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Hydrogels: SwellingHydrogels: Swelling

After polymerization, theAfter polymerization, the hydrophilichydrophilicgel isgel isbrought in contact with waterbrought in contact with water

The network expandsThe network expands

The thermodynamically drivenThe thermodynamically driven swelling forceswelling force isiscounterbalanced by thecounterbalanced by the retractive forceretractive force of theof thecrosslinked structurecrosslinked structure

Two forces become equal at some point andTwo forces become equal at some point andequilibrium is reachedequilibrium is reached


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Why is the degree of swellingWhy is the degree of swellingimportant?important?

solute diffusion coefficient through thesolute diffusion coefficient through thehydrogelhydrogel

surface properties and surface mobilitysurface properties and surface mobility

optical properties (particularly foroptical properties (particularly forcontact lens applications)contact lens applications)

mechanical propertiesmechanical properties


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Degree of swelling can be quantifiedDegree of swelling can be quantifiedby:by:

ratio of sample volume in the swollenratio of sample volume in the swollenstate to volume in the dry statestate to volume in the dry state

weight degree of swelling: ratio of theweight degree of swelling: ratio of the

weight of swollen sample to that of theweight of swollen sample to that of thedry sampledry sample


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Highly swollen hydrogels:Highly swollen hydrogels: cellulose derivativescellulose derivatives

poly(vinyl alcohol)poly(vinyl alcohol)

poly(Npoly(N--vinyl 2vinyl 2--pyrrolidone), PNVPpyrrolidone), PNVP poly(ethylene glycol)poly(ethylene glycol)

Moderately or poorly swollen hydrogels:Moderately or poorly swollen hydrogels: poly(hydroxyethyl methacrylate), PHEMA andpoly(hydroxyethyl methacrylate), PHEMA and

derivativesderivativesOne may copolymerize a highly hydrophilicOne may copolymerize a highly hydrophilicmonomer with other less hydrophilic monomersmonomer with other less hydrophilic monomersto achieve desired swelling propertiesto achieve desired swelling properties


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Hydrogels: PHEMAHydrogels: PHEMA

The most widely used hydrogelThe most widely used hydrogel

water content similar to living tissueswater content similar to living tissues

inert to biological processesinert to biological processesshows resistance to degradationshows resistance to degradation

permeable to metabolitespermeable to metabolites

not absorbed by the bodynot absorbed by the body

withstands sterilization by heatwithstands sterilization by heat

prepared in various shaped and formsprepared in various shaped and forms


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Hydrogels: PHEMAHydrogels: PHEMA

Properties depend on:Properties depend on:

polymer volume fractionpolymer volume fraction

degree of crosslinkingdegree of crosslinking temperaturetemperature

swelling agentswelling agent

combined with other acrylic monomers tocombined with other acrylic monomers toadjust propertiesadjust properties


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Hydrogels: ApplicationsHydrogels: Applications

Biomedical use due to bioBiomedical use due to bio-- and bloodand blood--compatibilitycompatibility

Pharmaceutical use due to hydrophilicityPharmaceutical use due to hydrophilicity(controlled/sustained drug release)(controlled/sustained drug release)

Earliest biomedical application contact lensesEarliest biomedical application contact lenses good mechanical stabilitygood mechanical stability

favorable refractive indexfavorable refractive index

high oxygen permeabilityhigh oxygen permeability

needs hygienic maintenance (does not apply for disposable)needs hygienic maintenance (does not apply for disposable)

lubricating surface coatinglubricating surface coating used with catheters, drainage tubes and glovesused with catheters, drainage tubes and gloves

nonnon--toxictoxic


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artificial tendon and cartilageartificial tendon and cartilagewound healing dressings (Vigilonwound healing dressings (Vigilon, Hydron, Hydron,,GelpermGelperm)) nonnon--antigenic, flexible wound coverantigenic, flexible wound cover permeable to water and metabolitespermeable to water and metabolites lowlow--strengthstrength

artificial kidney membranesartificial kidney membranesartificial skinartificial skin

maxillofacial and sexual organ reconstructionmaxillofacial and sexual organ reconstructionmaterialsmaterialsvocal cord replacementvocal cord replacement


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Pharmaceutical applicationsPharmaceutical applications monomer composition and relative amountsmonomer composition and relative amounts

of multiof multi--polymer hydrogels can be varied topolymer hydrogels can be varied to

alter the diffusion characteristic andalter the diffusion characteristic andpermeability of the gel containingpermeability of the gel containingpharmaceutical agentspharmaceutical agents

Methods for drug deliveryMethods for drug delivery drug gets trapped in the hydrogel duringdrug gets trapped in the hydrogel during

polymerizationpolymerization

drug introduced during swelling in waterdrug introduced during swelling in water


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Release occurs by outflow of drug fromRelease occurs by outflow of drug fromthe gel and inflow of water to the gelthe gel and inflow of water to the gel

Rate of diffusion is explained by FicksRate of diffusion is explained by Fickslaw:law:

J =J = --D dCD dCmm/dx/dx

J: flux (g/cmJ: flux (g/cm22sec)sec)

D: diffusion coefficientD: diffusion coefficient

CCmm: concentration of the diffusing material: concentration of the diffusing material


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Hydrogel: A Success StoryHydrogel: A Success Story

Otto Wichterle


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Otto WichterleOtto Wichterle

1939: his research was interrupted when the Nazis1939: his research was interrupted when the Nazisclosed the Czech universitiesclosed the Czech universities1958: he had to leave the Institute of Chemical1958: he had to leave the Institute of ChemicalTechnology after a political purge staged by itsTechnology after a political purge staged by its

Communist leadershipCommunist leadership1968: he lost his job as head of his own research1968: he lost his job as head of his own researchinstitute as a result of his participation in the Pragueinstitute as a result of his participation in the PragueSpring uprisingSpring uprisingnever gave up on his researchnever gave up on his research improvising equipment in his own homeimprovising equipment in his own home early prototypes for his invention were made in his kitchen onearly prototypes for his invention were made in his kitchen on

machines constructed from a bicycle dynamo and an oldmachines constructed from a bicycle dynamo and an oldphonographphonograph

Czech government sold the patent to the Americans, heCzech government sold the patent to the Americans, hedid not receive any royalties for his inventiondid not receive any royalties for his invention

Still used eyeglassesStill used eyeglasses


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The Cutting Edge.The Cutting Edge.

First implantable lens for nearsightedness wasFirst implantable lens for nearsightedness wasapproved by the Food and Drug Administrationapproved by the Food and Drug Administration

A surgeon slips the lens through a small incisionA surgeon slips the lens through a small incision

and implants it in front of the natural lens.and implants it in front of the natural lens.

Tiny hard plastic lens works behind the scenesTiny hard plastic lens works behind the scenesto help the eye create into help the eye create in--focus images.focus images.

An alternative to glasses, contact lenses or LasikAn alternative to glasses, contact lenses or Lasiksurgery for people who have trouble seeingsurgery for people who have trouble seeingdistant objects.distant objects.


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Already in use in Europe, the lens is manufactured by Ophtec USAAlready in use in Europe, the lens is manufactured by Ophtec USAInc., of Boca Raton, Fla., under the trade name Artisan, which willInc., of Boca Raton, Fla., under the trade name Artisan, which willbe distributed by American Medical Optics under the Verisyse brandbe distributed by American Medical Optics under the Verisyse brandname.name.Will cost $3,000 to $4,000 per eye, currently is targeted at patientsWill cost $3,000 to $4,000 per eye, currently is targeted at patients

who, for various reasons, can't get Lasikwho, for various reasons, can't get LasikRobert K. Maloney, an ophthalmology associate professor who hasRobert K. Maloney, an ophthalmology associate professor who hascorrected the vision of Cindy Crawford and Kenny G with Lasik.corrected the vision of Cindy Crawford and Kenny G with Lasik. 50 percent more accurate than Lasik.50 percent more accurate than Lasik. better quality of vision: The vision is crisper, brighter and clearerbetter quality of vision: The vision is crisper, brighter and clearer

92 percent of662 patients had 20/40 or better vision, considered92 percent of662 patients had 20/40 or better vision, consideredstandard vision necessary to obtain a driver's license, and 44standard vision necessary to obtain a driver's license, and 44percent had 20/20 or better, the FDA said, citing Ophtec research.percent had 20/20 or better, the FDA said, citing Ophtec research.


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May not eliminate the need for glasses for night driving or other activities performedMay not eliminate the need for glasses for night driving or other activities performedin low light.in low light.Count Rosalia de Firmian of Santa Barbara, among the grateful.Count Rosalia de Firmian of Santa Barbara, among the grateful. Her vision began deteriorating when she was 6 years old.Her vision began deteriorating when she was 6 years old. corrective contact lenses for40 years,corrective contact lenses for40 years, I can see my shoes, my slippers. Everything. I see the wall, the clock."I can see my shoes, my slippers. Everything. I see the wall, the clock."

others warn of the risk of patients developing cataracts or eyeothers warn of the risk of patients developing cataracts or eye--destroying infections.destroying infections. Balamurali Ambati, an ophthalmologist and corneal specialist at the Medical College ofBalamurali Ambati, an ophthalmologist and corneal specialist at the Medical College of

Georgia. "Anytime the eye is opened, bacteria can get in."Georgia. "Anytime the eye is opened, bacteria can get in." Nicholas Tarantino, vice president of global clinical research and development for AdvancedNicholas Tarantino, vice president of global clinical research and development for Advanced

Medical Optics, said no patients in the U.S. clinical trials developed cataracts.Medical Optics, said no patients in the U.S. clinical trials developed cataracts.

The FDA is requiring the company to do a followThe FDA is requiring the company to do a follow--up, fiveup, five--year study of users of theyear study of users of thelens to determine any side effects.lens to determine any side effects. One possible concern, FDA said, is the loss of endothelial cells in the corneas of patientsOne possible concern, FDA said, is the loss of endothelial cells in the corneas of patients

who received the implants.who received the implants. These cells form a layer on the undersurface of the cornea and are essential to keeping theThese cells form a layer on the undersurface of the cornea and are essential to keeping the

cornea clear.cornea clear. In the tests, there was a steady loss of endothelial cells of 1.8 percent a year.In the tests, there was a steady loss of endothelial cells of 1.8 percent a year. The FDA is requiring the lens label to specify it be used only in patients with a dense enoughThe FDA is requiring the lens label to specify it be used only in patients with a dense enough

layer of these cells to stand some loss over time.layer of these cells to stand some loss over time.

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Hydrogels (2)