lec6_natural materials as biomaterials

7/27/2019 Lec6_Natural Materials as Biomaterials

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NaturalPolymersasBiomaterials

SourceInformationforthefollowingslides:

1)Okada,M.Prog.Polym.Sci.2002,27,87133.

2)Nair,L.etal.Prog.Polym.Sci.2007,32,762798.

3)B.

Ratner,

A.

Hoffman,

F.

Schoen,

and

J.

Lemons:

BiomaterialsScience, 2nd

edition(SanDiego:ElsevierAcademicPress.2004).


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EnzymaticallyDegradablePolymers

ProteinsandPoly(aminoacids)

Collagen Naturalpoly(aminoacids)

Syntheticpoly(aminoacids) Poly(Lglutamicacid)

Poly(aspartic

acid)

Elastin

Elastinlikepeptides

Albumin

Fibrin

Polysaccharides Chitinandchitosan


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NaturalPolymers:Background

Egypt: Animalsinewusedforsutures

100:

Disemboweledsoldiers

treated

with

natural

biomaterials

1667: Bloodtransfusionwithlambblood

(France) 1700:Caranium transplantationfromdog(Russia)

1936:ArthurBowen(England)usedporcinesmall

intestineas

asoft

tissue

alternative.

Abundant

material,lowimmunogenicity


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NaturalPolymers:Background

Relevance:naturaltissuesinbiomedicineisamultibillion

dollarindustry

Fabrication:mostlylivingtissuesfromhumans(autograft,

allograft)or

animals

(xenograft)

that

have

been

decellularized

usingsterilants.

Applications:Heartvalves,meniscusregeneration,drug

delivery,sutures


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NaturalMaterials

Naturalmaterialsareoftensimilar,ifnotidenticaltomacromolecular

materialsthebiologicalenvironmentcanrecognizeandprocessthrough

metabolicpathways

Naturalmaterialscanfunctionbiologicallyatthemolecularlevel,notjust

macroscopiclevel

Inflammatoryresponse

invoked

by

synthetic

material

is

suppressed

with

naturalmaterials

Naturalpolymerscanoftenbedegradedbynaturallyoccurringenzymes

leadingto

the

material

being

metabolized

by

physiological

mechanisms

Isthisadisadvantage? Perhapsincertainapplications,butinothersitcanbequite

advantageous. Forexample,implantsdesignedtodeliveraspecificfunctionfora

temporaryamountoftime.

Crosslinksmakeless degradable


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NaturalMaterials

Disadvantagesofnaturalmaterials:

Similarityto

biological

substances

often

invokes

aimmunogenic

response

(thisisparticularlyaproblemforproteins). Bodysimmunesystem

recognizesforeignmaterialandattemptstodestroy.

High

degree

of

variability

in

natural

materials

derived

from

animal

sources

Structurallymorecomplexthantraditionalmaterials;manipulationmore

elaborateandcomplicated

Limitedprocessing

routes

in

many

cases


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NaturalPolymers:StructureandFunction

Whatstheconnectionbetweenbodilytissuesandpolymers?

FourPrincipleTissueTypes Epithelial linessurfacesandcavities;protectsstructures,fluidtransport

Connective fibrous,loadbearing

Muscle contractilefilaments;externalandinternallocomotion

Nervous muscleandmentalactivity

Principletissuesarelargelycomposedbythreetypesof

biopolymers:

Proteins chainsofaminoacids(silk,collagen,elastin,fibrin)

Polysaccharides chainsofsugar(chitin,glycosaminoglycans)

Polynucleotides chainsofnucleotides(DNA,RNA)


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Iftheconstituentmoleculesinnaturaltissuearesimilar,what

influences

the

material

properties?

Molecularconfiguration 29differenttypesofcollagenhavebeenidentifiedwithdifferentcrosslinksandstructuralhierarchies

Composition cartilagehas

30x

more

polysaccharides

than

ligament

Organization cartilageisisotropic,ligamenthasapreferreddirection

OverridingPrinciple: Natureadaptsstructuretoperformaspecificfunction


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Thestructuralelementsofthehumanbodyarethecellsand

the

extracellular

matrix

(ECM) the

cells

secrete

Inbiomaterials,wegenerallyusenaturalpolymersfromthe

ECMofconnectivetissues(e.g.tendon,skin,ligament,blood

vessels,cartilage,

bone


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NaturalPolymers Proteins

Protein

Structure:

Polymer:chainsofaminoacid

Bonding:covalent

peptide

bonds

Hydrophoblic core,hydrophilicexteriorinteractswithaqueous

environment

Proteinfoldinaspecificmannerforaspecificfunction(most

complicatedmacromolecules

in

the

human

body)

Function

Actasenzymes(assemble/disassembleothermolecules)

Also

serve

to

provide

structural

stability

(connective

tissue)


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Collagen

Collagenisthemostabundantproteinpresentinthehumanbodybeing

themajorcomponentofskinandothermusculoskeletaltissues.

Collagenisarodtypepolymernearly300 nmlongwithamolecular

weightof

300,000.

Morethantwentytwodifferenttypesofcollagenidentifiedsofarinthe

humanbody,withthemostcommonbeingTypeIIV.

TypeIcollagenisthesinglemostabundantproteinpresentinmammals

and

is

the

most

thoroughly

studied

protein. TypeIcollageniscomposedofthreepolypeptidesubunitswithsimilar

aminoacidcompositions.Eachpolypeptideiscomposedofabout1050

aminoacids,containingapproximately33%glycine,25%proline and25%

hydroxyproline witharelativeabundanceoflysine.


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CollagenTypes

Type StructuralFeatures RepresentativeTissues

Fibrillar Collagens

I 300nm

long

fibrils Skin,

tendon,

bone,

ligaments,dentin,

interstitialtissues

II 300nmlongfibrils Cartilage,vitreoushumor

III 300nm

long

fibrils;

often

withtypeISkin,

muscle,

blood

vessels

V 390nmlongfibrilswith

globularNterminal

domain;oftenwithtypeI

SimilartotypeI;alsocell

cultures,fetaltissues

SOURCE:K.Kuhn,1987,inR.Mayne andR.Burgeson,eds.,Structureand

Functionof

Collagen

Types,

Academic

Press,

p.

2;

M.

van

der

Rest

and

R.

Garrone,1991,FASEBJ.5:2814.


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StructuralOrderinCollagen

Structuralorderincollagenoccursatseveraldiscretelevels

Primarystructure sequenceofaminoacids

Secondarystructure

local

configurationofpolypeptidechainsthatresultsfromsatisfactionofstereochemicalanglesandhydrogenbonding

betweenpeptide

residues

Tertiary globalconfiguarations ofpolypeptidechains.triplehelicalcollagenmolecule

Quaternarydenotes

repeating

supramolecular unitstructurecomprisingseveralmoleculespackedintoaspecificlattice.Basicunitofthemicrofibril


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B.Ratner,A.Hoffman,F.Schoen,andJ.Lemons:BiomaterialsScience, 2ndedition(SanDiego:ElsevierAcademicPress.2004).134.

Collagenundergoesenzymaticdegradationwithinthebodyviaenzymes,suchascollagenases

andmetalloproteinases,

to

yieldthecorrespondingaminoacids.

Duetotheirenzymaticdegradability,uniquephysicochemical,mechanicaland

biologicalproperties

collagen

hasbeenextensivelyinvestigatedforbiomedicalapplications.

Collagenismostlysolubleinacidicaqueoussolutionsand

canbe

processed

into

different

formssuchassheets,tubes,sponges,foams,nanofibrousmatrices,powders,fleeces,injectableviscoussolutionsanddispersions.

Studieshave

also

shown

that

thedegradationrateofcollagenusedforbiomedicalapplicationscanbesignificantlyalteredbyenzymaticpretreatmentorcrosslinkingusing

variouscross

linking

agents.


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NaturalPolymers Polysaccharides


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B.Ratner,A.Hoffman,F.Schoen,andJ.Lemons:BiomaterialsScience, 2ndedition(SanDiego:ElsevierAcademicPress.2004).135.


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lec6_natural materials as biomaterials

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