MT 271

Topic 6
Polymeric biomaterials
 What is a polymer?
Long chain molecules
Smaller repeat units: monomer
Backbone (typically) consists of mostly C atoms

Natural polymers: polypeptides (proteins), polynucleotides (DNA,

RNA), polysaccharides (sugars)
Synthetic polymers: hydrophobic plastics, water-absorbing
hydrogels, etc.
 Classification of polymers
Polymers can be classified based on –
• Sources
• Chain structures
• Thermal behaviors
• Stabilities
 Polymer
source

Based on source:
naturally-occurring
vs. synthetic
 Polymer chain structure
Linear polymer:
• No chemical bonds between each polymer molecular chains.
• When heated or under stress, the molecular chains can move
relatively to each other.
• Can be dissolved in suitable solvents.
• When heated, the polymer can be molten.
• Therefore, linear polymers usually can be processed easily.
 Polymer chain structure

Branched polymer:
• similar chemical properties to linear polymer.
• physical properties of the branched polymer can be significantly
affected by the formation of branch chains.

high density polyethylene (HDPE)

low density polyethylene (LDPE)
 Polymer chain structure
Crosslinked polymer:
• Polymer chains linked together via chemical bonds to form a
3D network
• Cannot be dissolved in solvents
• Do not melt on heating
Polymers classified by thermal behavior
Thermoplastic —

Can be remelted and reprocessed

Both linear and branched polymers

Thermosetting —

Cannot be remelted and reprocessed

Crosslinked three dimensional or network polymers
 Polymers classified by stability
Classified based on their stability when they are used in contact with
biological systems-
• Biostable
• Biodegradable

In biodegradable polymers, degradation is mediated at least partially

by a biological system; caused by-
• Hydrolytic
• Enzymatic
• Bacteriological degradation processes

Degradation → Change in chemical structure → change in physical

properties
Examples of biodegradable polymers
 Molecular weight, polydispersity
Molecular weight: average of a distribution of molecular weights
Number average molecular weight: Mn
Weight average molecular weight: Mw

Polydispersity index (PI): measure of

distribution span of molecular weights
PI = Mw / Mn
 Tacticity

Tacticity is the arrangement of substituents around the polymer backbone

chain.

Isotactic: All substituents are located on the same side of the zigzag plane

Syndiotactic: Substituents alternate from side to side.

Atactic: Substituent groups appear randomly

Tacticity affects polymer crystallinity

 Crystallinity
Polymers can be either amorphous or
semicrystalline.

Never completely crystalline owing to lattice defects

that form disordered, amorphous regions.

Tendency to crystallize enhanced by small side

groups and chain regularity.

The presence of crystallites leads to better

mechanical properties.

Thus, semicrystalline polymers (often referred to

simply as crystalline polymers) desirable materials
for biomedical (load-bearing) applications.
 Mechanical properties

Amorphous, rubbery polymers:

• soft (low modulus)
• reversibly extensible (> 100%)

Glassy and semicrystalline polymers:

• stiffer (higher modulus)
• lower extensibilities
• often brittle (catastrophic failure)
• some polymers show yielding

Fatigue properties important for dynamic loading

e.g., artificial hearts or LVADs
 Thermal properties Stiff glassy state

Tm = melting temperature

A crystalline polymer melts above Tm

At T > Tm, polymer crystals begin to

fall apart or melt. Chains come out of
Flow region
their ordered arrangements, and
begin to move around freely.

Rubbery state: long-range segmental motion occurs but

thermal energy cannot overcome local chain entanglement

Tg= glass transition temperature

For an amorphous polymer, when T > Tg, polymer is soft and rubbery
For T < Tg, polymer is hard and brittle, like glass.

Tm > Tg
 Tg and polymer usage
Some polymers are used below their Tg, (Tg > Room Temp) in hard
glassy state

e.g. polystyrene, PMMA (Tg ~ 100 C)

Other polymers used above their Tg (Tg < Room Temp) in a soft,
rubbery state.

e.g., polyisoprene and polyisobutylene

 Addition polymerization
Unsaturated monomers (contain double bonds) react to form the
polymer product.

Example: polyethylene, PVC, PMMA

 Addition polymerization
Three stages:

1. Initiation: Opening of the double bond on the monomer by the

initiator (free radicals, cations, anions, and coordination catalysts
generated by heat, UV, chemical reaction, etc.)
 Addition polymerization
Three stages:

2. Propagation: Free radical can continue to react with monomers

 Addition polymerization
Three stages:

3. Termination: The reaction is terminated by reaction with another

radical, a solvent molecule, another polymer molecule, an initiator, or
an added chain transfer agent
Typical addition polymers
 Condensation polymerization
Two monomers react to form a covalent bond, usually with elimination
of a small molecule such as water, HCl, or carbon dioxide.

Examples: Nylon, poly(ethylene terephthalate) (PET)

Sometimes no small molecule is released, also called polyaddition

Examples: Polyurethane
Typical condensation polymers
 Polymer structure
Homopolymers: contain only one type of repeat unit
Copolymers: two or more types of repeat units.

Copolymer can be:

• random
• alternating
• graft
• block
Homopolymer biomaterials
Copolymer biomaterials
 Synthetic non- biodegradable
polymers for bio-applications

Silicones
Polyethylene
Polymethyl methacrylate
Polyester
Polycarbonates
Polyamides
Polyurethanes
etc….
 Silicones
Category of synthetic polymers whose backbone is made of
repeating silicon to oxygen bonds.

The silicon atoms are also bonded to organic groups, typically

methyl groups.
 Silicone applications
Possible uses as fluids, emulsions, resins, and elastomers:
• In electronics: used as electrical insulation
• Silicone sealants, adhesives and waterproof coatings in the
construction industry
• Used in personal care, pharmaceutical, and medical device
applications.

Desirable/useful properties:
• Chemical stability
• Thermal stability
• Low surface tension
• Elastic nature
 Silicone in orthopedic applications
Hand and foot implants
e.g., artificial finger joints
 Silicone tubes
Used to make catheters, shunts, drains, etc.

Used as coating due to good blood-compatibility: Hypodermic

needles, syringes, and other blood-collecting apparatus are coated
and/or lubricated with silicone.

Occluder ball in mechanical

heart valve
 Silicone for reconstructive surgery
Widely used for reconstructive/ asthetic surgeries for-
breast, scrotum, chin, nose, cheek, calf, and buttocks.

May employ a softer-feeling substance known as silicone gel (a lightly

cross-linked silicone elastomer)

Silicone also used for surface patterning/ stamping (soft lithography)-

to be discussed in lecture on surface modification of biomaterials.
 Polyethylene (PE)

3 type of polyethylene:

• linear high density polyethylene (HDPE),

• branched low density polyethylene (LDPE)
• ultrahigh molecular weight polyethylene (UHMWPE)

HDPE and UHMWPE used as biomaterials.

 HDPE
HDPE is “bioinert” (low tissue reactivity)- low inflammatory response

Used as bone and cartilage substitutes since 1940s.

HDPE is used as a standard reference material for biocompatibility

testing

Fibrous tissue ingrowth into porous HDPE → improved fixation

MedPor (Porex Surgical Inc.) is porous HDPE

Pore size > 100 mm encourages tissue ingrowth (vascularization)

Used for craniofacial applications, such as chin, nasal reconstruction,

ear reconstruction, etc.
HDPE implants from MedPor

http://www.porexsurgical.com/products/medpor-implants
 UHMWPE
Used to manufacture the liner of the acetabular cup in total hip
arthroplasties (THAs) and the tibial insert and patellar component in total
knee arthroplasties

Attractive properties:
• exceptional mechanical properties
• chemical inertness
• impact resistance
• low coefficient of friction

Problem:
Wear debris of UHMWPE evokes a chronic inflammatory response
Particles are phagocytosed → formation of lesions, osteolysis, and bone
resorption.
 PMMA
Methyl methacrylate (MMA) + Initiator + Heat →
Poly (methyl methacrylate) (PMMA)

Used as bone cement (since 1950s) for anchoring

orthopedic implants to the bone tissue

KyphX® HV-R™ Bone Cement is the first PMMA bone

cement indicated for use in Balloon Kyphoplasty
procedures. KyphX HV-R Bone Cement is specifically
formulated to allow extended working time for delivery into
bone under manual control.
 Polyester
Family of polymers involving the ester linkage

Poly(ethylene terephthalate) (PET): used to make synthetic fibers and

films

PET fibers (woven, knitted, felted and braided structures)used as-

• sutures (Mersilene™ and Ethibon™)
• internal patches,
• ligamentous prosthesis
• artificial blood vessels
• heart valve sewing cuffs, etc.
PET sutures and patches
 Polycarbonates
Family of polymers involving the carbonate linkage

Tough, transparent plastics

Makrolon™ 2558 is used to make components for:

• oxygenator for open heart surgery, venous reservoir, and arterial filter
due to-
• sterilizability, ease of processing, biocompatibility, and clarity.
 Polyamides
Family of polymers involving the amide linkage

Polycondensation of hexamethylenediamine and adipic acid: Nylon-66

Different types of nylons prepared by changing the dicarboxylic acid and

diamine

Nylon used as surgical sutures:

Ethilon™ (Nylon-6) and Nurolon™ (Nylon-66)
 Polyurethane

Polyurethanes are a class of polymer

with urethane linkage

Synthesized by the reaction of dihydric alcohols and diisocyanates.

 Polyurethane
Polyurethane elastomers-
• excellent fatigue resistant properties and “biocompatibility”
• are segmented block copolymers containing hard and soft segments
• hard segments aggregate in domains held together by hydrogen
bonding between the urethane segments
• hard segment acts as a physical cross-linking point.
• soft segments are dihydroxy terminated long chain macroglycols with
low Tg.
Synthetic biodegradable polymers
• Eliminated (safely) from the body after intended use

• Degradation product must be non-toxic (often

metabolites present in vivo)

• But critical to control the degradation rate (must

closely match with tissue growth)
Mechanisms of degradation
 Aliphatic polyester
Hydrolysable ester linkages in their structure
 Aliphatic polyester synthesis
by the step growth condensation polymerization of hydroxyacids

by the step growth condensation polymerization of diols and diacids

by ring opening polymerization of heterocyclic monomers bearing at

least one ester bond in the monomer structure
 Poly(glycolide)
PGA is synthesized through the ring opening polymerization of glycolide

PGA is highly crystalline (45% -55%)

So, PGA fibers exhibit high strength and modulus
But too stiff to be used as sutures except as braided material.

Used to make biodegradable sutures:

• 50% strength of fibers lost in two weeks
• 100% after four weeks
• completely absorbed in 4 - 6 months
 Poly(lactide)
PLA synthesis similar to PGA, prepared from lactide

Lactic acid is a chiral molecule

Two stereo-isometric forms: D-LA and L-LA (naturally occurring)

P(D,L)LA is a synthetic blend of PLLA and PDLA

PLLA and PDLA are crystalline: high strength and modulus
PDLLA blends are amorphous/ low-crystalline

PLLA used as for bone reconstructions, articular defects, suture materials,

drug carriers, and fixation devices

PLA degrades into natural LA; degradation too slow so use PDLLA blends
 Biodegradable polymer devices

BioScrew® Bioabsorbable Interference Screws

Clinically equivalent to metal interference screws
Made of Poly (L-Lactic Acid), the screw is gradually absorbed and eventually disappears
BioScrew® screws have a long-term absorption rate which ensures secure graft fixation throughout the healing process
Any future revision surgery is free of implant removal complications because the screw is absorbed or can simply be overdrilled
BioScrew® screws are packaged sterile, single use
The BioScrew® tri-lobe driver accepts the Guardsman® graft protector as an optional protective barrier between the screw and graft
 Poly( lactide-co-glycolide)
PLGA prepared by copolymerization of lactide and glycolide
 Poly( lactide-co-glycolide)
Vary ratio of LA and GA to vary mechanical properties and degradation
rates

Degradation rate is not linear with composition

Half-lives as follows-

Used for resorbable device, drug delivery applications and as 3D

tissue scaffolds

For example- 82/18 poly (L-lactide-co-glycolide) copolymers used as

suture anchors and as screws and plates for craniomaxillofacial repair
 Poly (e-caprolactone)
Synthesized through the ring opening polymerization of e-caprolactone

• Semi-crystalline polymer
• Slow degradation
• Copolymerized with DL-lactide to
increase degradation rate
• Degradable sutures
 Poly amino acids
Polyamino acid is desirable because:
• the peptide linkage can be broken down enzymatically.
• degradation products then would be amino acids and polypeptide
(non-toxic)

Challenges:
• Antigenicity (immune response) of the polyamino acid with > 3 amino
acids in their structure.
• Therefore, use polymer of single type of amino acid, e.g., poly( L-
lysine), poly-L-glutamic acid.
• These polymers are high crystalline → difficult to process

To overcome these problems, a modified "pseudo" poly( amino acids)

has been synthesized using a tyrosine derivative
 Tyrosine-derived polycarbonates
To overcome limitations of poly amino acids, tyrosine derivatives were
developed

Reva Medical’s ReZolve™ stent incorporates a

proprietary tyrosine-derived polycarbonate polymer
that provides visibility under X-ray during the
implant procedure and at follow up, but dissolves
from the body after it is no longer needed, leaving
the patient free of a permanent implant.
 Fibers and
textiles
Applications-
• Bandages, Wound dressing
• Vascular grafts
• Tissue scaffolds
 Medical fibers

Common means of processing-

• Melt spinning
• Wet spinning
• Electro-spinning
 Melt spinning
Resin is heated above its melting temperature and
extruded through a spinneret.

The number of holes in the spinneret = number of

filaments in the fiber

54-multifilament yarn is commonly used in vascular

graft construction.

Aorti graft (InterGard Woven Aortic Thoracic Graft;

InterVascular, La Ciotat, France).
 Wet spinning
For polymer systems that degrade at elevated temperatures

Polymer is dissolved in a solvent and then extruded through a spinneret

into a non-solvent in a spin bath.

The solvent is soluble in the spin bath, but the polymer is not, the
continuous polymer stream precipitates into a solid filament

Fiber diam. 10 μm to 500 μm or thicker

 Electrospinning
A polymer solution or melt is extruded through a syringe
in a high voltage (5-30 kV) electrostatic field.

Electrostatic charge build up overcomes surface tension

ejecting a jet of liquid towards the collector (grounded
target)

Solvent evaporates to form fiber mats on collector

Variables determining fiber diameter-

• Polymer chemistry and/or solvent choice
• Polymer solution/melt viscosity
• Strength of the applied electric field
• Geometry and operating conditions

Fiber diameters: 100 nm to 1 μm

 Fibers processed into biotextiles
Fiber → Yarn → Textiles for better mechanical and biological properties.

Typical biotextile structures used for medical applications-

• Non-wovens
• Wovens
• Knits
• Braids

Choice based on compromises/ optimal properties:

• Woven fabrics stronger with lower water/blood permeability than knits

• Knits are more flexible and easy to handle/ suture

• Braids have great flexibility, but can be unstable under longitudinal

load
 Hydrogels
Water-swollen, cross-linked polymeric structures formed by-
• covalent bonds,
• physical cross-links from entanglements, or
• association bonds such as hydrogen bonds or strong van der Waals
interactions between chains

Hydrogels classified as-

(i) homopolymer hydrogels: one type of hydrophilic monomer unit
(ii) copolymer hydrogels: two monomers, at least one is hydrophilic
(iii) multipolymer hydrogels: ≥ 3 monomers
(iv) interpenetrating network hydrogels: preparing a first network that is
swollen in a second monomer, which polymerizes to form a second
intermeshing network
 Hydrogel structure

(A) Ideal macromolecular network

(B) Network with multifunctional junctions
(C) Physical entanglements
 Hydrogel preparation
Hydrogels are prepared by swelling cross-linked structures in water/
buffers/ biological fluids.

Methods of preparation of the initial networks include chemical cross-

linking, photopolymerization (UV light), or irradiative cross-linking
(electron beams, gamma rays, or X-rays)

Common examples of hydrogels-

• Highly swollen hydrogels: cellulose derivatives, poly(vinyl alcohol),
poly(N-vinyl-2-pyrrolidone) (PNVP), poly(ethylene glycol) (PEG)

• Poorly swollen hydrogels: poly(hydroxyethyl methacrylate)

(PHEMA) and its derivatives.
 pHEMA
Poly(2-hydroxyethyl methacrylate) (pHEMA) is
used for soft contact lens:

• Inert to normal biological processes,

• Shows resistance to degradation,
• Is permeable to metabolites,
• Is not absorbed by the body,
• Is biocompatible,
• Withstands heat sterilization without damage,
• Can be prepared in a variety of shapes and
forms
 Poly(ethylene glycol) (PEG)
Also known as polyethylene oxide (PEO) or polyoxyethylene (POE)

Polymer of ethylene oxide

PEG molecules are highly soluble in water

PEG chains can be chemically crosslinked to make hydrogels

Many biotechnology and biomedical uses

• Cosmetics, creams, shampoos,

toothpaste, etc.
• As precipitant for protein/DNA/virus
crystallization/isolation
• Nanoparticles for drug delivery PEG conjugated to Interferon: for
• Scaffolds for tissue engineering treatment of Hepatitis infection
 Dendrimers and star polymers
A macromolecule characterized by
its highly branched 3D structure
that provides a high degree of
surface functionality and
versatility

• High degree of branching,

• Multivalency
• Globular architecture
• Well-defined molecular weight

Therefore, used as nanocarriers in

biomedical applications (drug
delivery, gene transfection, tumor
therapy, diagnostics, etc.)
 Stimulus-responsive polymers
Stimulus-responsive/ “intelligent”/
“smart”/ “environmentally sensitive”
polymers respond with sharp, large
property changes to small changes in
physical or chemical conditions.
Reversible response to stimulus
 Polymer–biomolecule hybrid

Polymer–biomolecule hybrid
systems can respond to
biological as well as to physical
and chemical stimuli.

Biomolecule may be chemically

crosslinked/immobilized or
physically mixed with the
polymer. e.g, polymer-protein
and polymer-drug combinations
 PNIPAAm
poly(N-isopropyl acrylamide) exhibit thermally induced precipitation

Polymer is soluble in water < 32C

Precipitates sharply as temperature > 32C

The precipitation temperature is called the lower critical solution

temperature (LCST)

Cells cultured to confluent sheets on surfaces

at 37C (> LCST)

At T < LCST, PNIPAAm chains rehydrate and

the cell sheets released from the surface

Used for tissue engineering (harvesting

confluent cell sheets) and drug delivery