natural bio polymers
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Introduction:y Biopolymers are polymers formed in nature during the
growth cycles of all organisms; hence also reffered to as Natural or Biological polymers.
y
Their synthesis always involves enzyme catalyzed chaingrowth polymerization reactions of activated monomerswhich are generally formed within the cells by complexmetabolic process.
y
The structure and properties of a given biological materialdepend on chemical and physical nature of components present and the relative amount.
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PROPER TIES OF BIOLOG ICA L MAT ER IALy Viability: Most biological materials are continuously
bathed with body fluids.y Most biological materials can be considered as
composites.y P roblems of toxicity and stimulation of a chronic
inflammatory reaction, as well as lack of recognitionby cells, which are frequently provoked by many
synthetic polymers, is suppressedy ability to be degraded by naturally occurring enzymes.
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TYPES OF NATURAL POLYMERS
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PROTEINS:y P roteins are linear,unbranched polymers constructed
from 20 standard amino acid.y Are polyamides formed by step-reaction
polymerization between amino and carboxyl groups of
amino acids
where R is a side group. Depending on the side group, the molecular structurechanges drastically
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Am ino acid: Bas ic unit of p roteinAm ino acid: Bas ic unit of p rotein
COO -NH3
+ C
R
H
Different side chains, R, determin theproperties of 20 amino acids.
AMINOGROUP
C ARBOXYL
GROUP
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20 DIFFERENT AMINO ACID
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H ier a rchic al na ture of p rotein H ier a rchic al na ture of p rotein structurestructure
P rimary structure (Amino acid sequence)
Secondary structure -helix, -sheet
Tertiary structure Three-dimensional structure formed by assembly of secondary structures
Q uaternary structure Structure formed by more than onepolypeptide)
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COLLAGENy
C ollagen is a structural protein found in bone,cartilage, tendon, ligament, skin, and in the structuralfibers of various organs.
y collagen, has the general amino acid sequence X GlyP ro Hypro Gly X (X can be any other amino acid)arranged in a triple -helix.
y Fundamental unit of collagen is tropocollagenconsisting of 3 coiled polypeptides called chains
which wind around one another to form a right
handed triple helix.y Different types of chains combining various ways to
give 19 different types of collagen in which type I, II &III represent 90% of collagen
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Contd ..
y The primary factors stabilizing the collagen molecules are invariably related tothe interactions among the -helices. These factors are H bonding between theC=O and NH groups, ionic bonding between the side groups of polar aminoacids, and the interchain crosslinks between helices.
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The collagen fibrils (2040 nm in diameter) form fiber bundles with a 0.21.2 mdiameter.
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BIOMATERIAL APPLICATION OFCOLLAGEN
y The collagen molecule is subject to modification by a large variety of chemical reagents
y the increasing use of collagen in biomaterials applications hasprovided renewed incentive for novel chemical modification,primarily in two areas.
y First, implanted collagen is subject to degradative attack by collagenases, and chemical cross-linking is a well-known meansof decelerating the degradation rate.
y Second, collagen extracted from an animal source elicitsproduction of antibodies (immunogenicity) and chemical
modification of antigenic sites may potentially be a useful way tocontrol the immunogenic response.y It is used in variety of forms such as solution,gel
fibers,membranes,sponges and tubing for biomedicalapplication.
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A pplications Physical stateS utures E xtruded tape
Hemostatic agents P owder, sponge, fleeceBlood vessels E xtruded collagen tube, processed human
or animal blood vesselHeart valves P rocessed porcine heart valveTendon, ligaments P rocessed tendonBurn treatment (dermalregeneration)
P orous collagenglycosaminoglycan(G AG ) copolymers
P eripheral nerveR egeneration
P orous collagen G AG copolymers
Meniscus regeneration P orous collagen G AG copolymersSk in regeneration(plastic surgery)
P orous collagen G AG copolymers
IntradermalAugmentation
Injectable suspension of collagen particles
G ynecologicalApplications
S ponges
Drug-delivery systems Various forms
Tissue scaffold
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ELASTINy
Elastin is another structural protein found in a relatively large amount in elastic tissues such as l igamentum nuchae(major supporting tissue in the head and neck of grazinganima l s), aortic wall, skin, etc.
y The high elastic compliance and extensibility of elastin isdue to the crosslinking of lysine residues via desmosine,isodesmosine, and lysinonor l eusine.
y Elastin is very stable at high temperature in the presence of various chemicals due to the very low content of polar side
groups (hydroxyl and ionizable groups).y Insoluble elastin preparations can be degraded by the
enzyme elastase
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Elas tin as a B ioma teri al
Elastin (-like) biomaterials have been suggested for a wide variety of applications, including
y skin substitutes,y
vascular grafts,y heart valves, andy elastic cartilage
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FIBRINy Fibrin has been used as a sealant and an adhesive in
surgery as it plays an important role in natural woundhealing
y Fibrin gels can be produced from the patient s ownblood and used as an autologous scaffold for tissueengineering
y Fibrin gels may promote cell migration, proliferationand matrix synthesis through the incorporation of platelet derived growth factors and transforminggrowth factor. It have also been used to engineertissues with skeletal muscle cells, smooth muscle cellsand chondrocytes
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NUCLEIC ACID:y Nucleic acids are polymers of nucleotides that have a
sugar, nitrogen base, and phosphate
Nucleotides are joined by Phosphodiester bond.
PO 4
Sugar
Base
NUCLEOSIDE
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Two types of Nucleotides (depending onthe sugar they contain)1- Ribonucleic acids (RNA)The pentose sugar is
Ribose (has a hydroxylgroup in the 3 rd carbon---OH)
2- Deoxyribonucleic acids(DNA)
The pentose sugar isDeoxyribose (has just anhydrogen in the same place--- H) Deoxy = minusoxygen
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D NA vs RNAy DNA
1- Deoxyribose sugar2- Bases: Adenine, Thymine, Cytosine, Guanine3- Double-stranded helix arrangement
y RNA1- Ribose sugar2- Bases: Adenine, Uracyl, Cytosine, Guanine4- Single stranded
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H ow D NA Works1- D N A stores genetic information in segments called genes
2- The D N A code is in Triplet C odons (short sequences of 3 nucleotides each)3- C ertain codons are translated by the cell into certain A minoacids.4. Thus, the sequence of nucleotides in D N A indicate a sequence of
A mino acids in a protein.CEN TR AL D OGM A:
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Polynucleotides PolypeptidesApplications
y P olynucleotides are potent interferon inducers. A mismatched double stranded syntheticpolyribonucleotide ampligen and the double strandedacids, polyadenylicpolyuridylic acid and polyinosinicpolycytidylic acids, have been studied for cancertherapy.
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POLYSACCH ARIDES
y Polysaccharides are polymers of monosaccharidesy Monosaccharide units are joined by glycosidic
linkage & these monosaccharides are simplesugars composed of simple polyhydroxy aldehydeor ketone unit.
y May be linear or branchedy Degree of polymerization (DP) in the range 200-
3,000S ome are even larger (DP 7,000-15,000)
y Nomenclature: glycans
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y 2 T Y P ES:y HOMO P OLY S A CC HARIDES contain only single type
of monomeric unit. Eg: starch, glycogen, cellulose,chitin.y HETEROP OLY S A CC HARIDES: contain 2 or more
different kinds of monomeric unit. These are of two
types:1. Glycosaminoglycans: negatively charged
heteropolysaccharides comosed of repeatingdisaccharide units. Eg: hyaluronic acid, heparin,
heparan sulfate and keratan sulfate2. P eptidoglycan or murin
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ont . y the repeat unit consisting of a hexosamine
(glucosamine or galactosamine) and of another sug ar(galactose, glucuronic acid, or iduronic acid).
y The molecular weight of many GAGs is in the range 560 kDa with the exception of hyaluronic acid, the only GAG which is not sulfated; it exhibits molecular
weights in the range 50 500 kDay Sugar units along GAG chains are linked by or
glycosidic bonds .y
There are several naturally occurring enzymes whichdegrade specific GAGs, such as hyaluronidase andchondroitinase. These enzymes are primarily responsiblefor the physiological turnover rate of GAGs,
which is in the range 2 14 days
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Gags as b ioma teri alsy Hyaluronic acid: The very high molecular weight of hyaluronic acid is
the basis of most uses of this GAG as a biomaterial.y Almost all make use of the exceptionally high viscosity and the facility to form gels that characterize this polysaccharide.
y Hyaluronic acid gels have found considerable use in ophthalmology because they facilitate cataract surgery as well as retinal reattachment
y
Other reported uses of GAGs are in the treatment of degenerative jointdysfunction in horses and inthe treatment of certain orthopedic ysfunctions in humans.
y sulfated GAGs are anionically charged and can induce precipitation of collagen at acidic pH levels, a process that yields collagen GAGcoprecipitates that can be subsequently freeze-dried and covalently cross-linked to yield biomaterials that have been shown capable of inducing regeneration of skin (dermis), peripheral nerves, and theconjunctiva
y Heparin find application for improving blood compatability of othermaterials, used as coating to prevent clots, and used for wound healing
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COMMONLY FOUND GAGs
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CELLULOSE & DERIVATIVESy These are structral component of plant cell wall and
accounts for half of carbon in the boisphere.y It also occur in marine invertbrates and microorganismy It is linear polymer consisting of D glucose residue linked
by b(14) glycosidic bond.this highly cohesive hydrogen
bonded structure give its fibre exceptional strength andmake it water insoluable.y It is degraded by specific cellulase enzymes. But vertebrates
donot posses any enzyme which can degarade it.y B coz of its infusibility and insolubility, it is converted into
derivative to make it processable. Important derivatives of cellulse are reaction product of 1 or more or three hydroxyylgroups which are present in each glucopyronosiderepeating unit.
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CH ITIN AND CH ITOSANy C HITIN & C HITOS AN:y
C hitosans are partially or fully deacetylated derivatives of chitin primary structuralpolymer in arthropod exoskeletonsy The primary source of chitin and chitosans is shells from crab,shrimp and lobster.
Most promising polysaccharide biomaterials for development of resorbableand biologically active implants
a. Found to be the most effective Immunomodulator for the activation of nonspecific host resistance against bacterial viral infections and tumourgrowth in mice.
b. Nonwoven fabrics made of chitin and chitosan fibres used for wounddressing
c. C omposite films used for manufacturing adhesive bandages for oral surgery methylpyrrolidone derivatized chitosan has been reported to promotebone formation.
y C hitosan has been modified with sugar residues such as fructose orgalactose for culture hepatocytes and with proteins such as collagen, gelatin andalbumin for neural tissue engineering
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ALGINATE AND DEXTRANy Dextran is a nontoxic biodegradable polymer and is
widely used in many biomedical areas.y Solution of Dextran has been used as surgical aids for
reducing tissue adhesion.y It have been in used for drug conjugation, via reductive
amination, to obtain large molecular weight drugderivatives for the purpose of altering drugdistribution after intravenous injection
y Alginic acids or alginates are isolated from several
species of brown algae (e.g., M
acroc ystis p yrifera)y Alginate have applications as an injectable cell delivery vehicle as well as wound dressing, dental impressionand immobilization matrix.
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REFERENCES:y P ARK, J. B. (1990). B iomateria l science and
engineering . New York, P lenum P ress.y RA TNER, B. D. (2004). B iomateria l s science: an
introduction to materia l s in medicine . Amsterdam,Elsevier Academic P ress.
y NARAYAN, R. (2009).B iomedica l materia l s. New York,Springer. http://dx.doi.org/10.1007/978-0-387-84872-3.
y BHA T, S. (2007). B iomateria l s. India, Narosapublishing house pvt ltd.
y DAAMEN, W. F. (2006). E l astin as a biomateria l for tissue engineering . S.l, s.n.]