Application of biomaterials in

Medicine and dentistry

 Cardiovascular applications
ØCardiovascular disease
continues to be the leading
cause of mortality and
morbidity in the world
resulting in 17 million deaths.
ØThe number is expected to
grow to more than 23 million
by 2030.
ØCoronary heart disease and
valvular heart disease are
more common
 Heart valves
ØA heart valve normally allows blood to flow in only one direction.
Human heart contains four valves: tricuspid valve, pulmonary valve,
mitral valve, and aortic valve.
ØDisorders of heart valves can cause
stenosis (obstruction to flow) or
regurgitation (reverse flow across the
value)
ØSome diseases such as infective
endocarditis (infection of a heart
valve) or calcific aortic stenosis results
in abrupt heart failure.
ØA: Severe calcification of tricuspid
aortic valve
ØB: Mitral stenosis (chronic rheumatic
heart disease) – scarring and stiffening
of the mitral leaflets
ØC: Mitral regurgitation – the strength
of the mitral valve decreases there by
causing the valve leaflets to deform
excessively.
ØAn artificial heart valve is a one-way valve implanted into a person’s
heart to replace a heart valve that is not functioning properly.

ØArtificial heart valves can be separated into three broad classes

1) Mechanical heart valves

2) Bioprosthetic tissue valves

 Mechanical heart valves
Ø1952: Dr. Charles Hufnagel designed and implanted a mechanical
heart into a thirty year old female (regurgitation flow was prevented
but coronary flow was not improved)

Ø1960: The Starr-Edwards ball valve was created.

Ø1969: The Bjork-Shiley valve started being used and it was based on
a tilting disc design

Ø1979: Bileaflet valves start being used and up to this day, their
designs are still being improved upon.
ØStarr-Edwards Ball-in-cage valve
ü When the pressure exerted by the heart onto the blood (and the ball)
exceeds the pressure in the aorta, the ball is pushed away from the
heart
ü This is the open position of the valve
and blood can flow out of the heart
into the aorta. After the heart ejects
blood, the pressure inside the heart
is greatly reduced so blood will try
to flow back inside the heart.
ü The negative pressure sucks the ball
valve backwards. It fits over the
opening of the heart and prevents
backflow of blood.
ØBjork-Shiley valve
ü Tilting disc valves can open at angle of 60° and at a rate of 70 beats
per minute

ü The angular opening of this valve reduces damage to blood cells

ü There are major over the ball design but the struts of the tilting disc
valves tend to fatigue and fracture over long periods of time.
ØBileaflet valve
ü Two semicircular leaflets that rotate about struts attached to the valve
housing
ü Food hemodynamics performance – improved flow characteristics,
lower transvalvular pressure gradients, less blood flow turbulence,
improved hemodynamics at a given annular diameter, a large orifice
area
ü The least thrombogenic of the artificial valves
ü Most commonly used
ØBiomaterials used
ü Pyrolytic carbon is another valuable material for its strength and its
ability to prevent clotting

ü This material has a similar structure to graphite.

ü It is biocompatible, thromboresistant, resistant to wear, and has high

strength and durability

ü It is able to stand up to the repeated opening and closing cycles it

must endure when used in mechanical heart valve

ü It is commonly used for the inner orifice and the leaflets of bileaflet
valves.
ü A material often used for the suture ring (which is used to attach the
valve to the body) is Dacron.
ü Dacron is a long chain polyester made from ethylene glycol and
terephthalic acid. It is a synthetic fiber that has many used in industry ,
including thermal insulation and sails for boats.
ü In biomedical applications this material is also commonly used for
vascular grafts. It is relatively inert and its porosity allows tissue in
growth.
ü Another material that is commonly used for the suture ring is Teflon
ü Teflon is used in many medical applications because of its signature
low coefficient of friction
ü Teflon is relatively inert and highly biocompatible. As with Dacron it is
often used for vascular grafts.
ØAdvantages
ü Mechanical valves are highly durable
ü Last around 25-35 years, since they are usually made from titanium
and/or carbon

ØDisadvantages
ü Increased risk of blood clotting
ü Back flow
ü Patients must take blood thinning medication and get blood tests
done every 4-6 weeks
ü Tend to get worn out
 Bioprosthetic tissue valves
ØBioprosthetic valves are made entirely or partly of materials of
biologic origin.
ØThey are classified as
1. Homografts (prepared from human cadevers-allografts)
2. Heterografts(prepared from tissues of another species-xenografts)
Ø Homografts are obtained by autopsy and stored in antibiotic
containing solution or freeze-dired
Ø Cryopreserved homografts valves have fewer complications
compared to mechanical or xenograft valves. They have good
hemodynamics and good durability
Ø But they are not widely used due to limited availability, difficulties
in obtaining valves of the size required, and complexity of the
implant technique.
ØAnimal tissue valves are often referred to as heterograft or
xenograft valves.
ØXenografts are made of either porcine aortic valve or bovine
pericardium.
ØHaving a trileaflet configuration with a central orifice, tissue valves
resemble natural valves.
ØThese bioprosthesis valves composed of three cusps of tissue
derived from either a porcine (pig) aortic valve or bovine (cow)
pericardium, each treated with glutaraldehyde.
ØGlutaraldehyde appears to promote stability of collagen cross-links
and renders the valves virtually nonantigenic.
ØGlutaraldehyde fixation preserves the tissue, decreases its
immunological reactivity, and kills the cells within the valve tissue
 Carpentier-Edwards
bovine pericardial
Hancock porcine valve valve
Porcine valves
ØThe valve tissue is sewn to a metal wire stent, often made from a
cobalt-nickel alloy

ØThe wire is bent to form there U-shaped prongs.

ØA Dacron cloth sewing or Teflon covered sewing is attached to the

base of the wire stent, and then the stents themselves are also
covered with cloth.

ØPorcine valves have good durability and usually last for ten to
fifteen years.
Bovine pericardial valves
ØAre similar to porcine valves in design

ØThe major difference is the location of the small metal cylinder

which joins the ends of the wire stents together

ØPericardial valves have excellent hemodynamics and have durability

equal to that of standard porcine valves after 10 year

ü Calcification is believed to be accelerated by high bending and

leaflet deformation.
ü These valves are less prone to thromboembolic problems and
therefore anticoagulant therapy is not necessary
 Pacemakers

ØPacemakers were developed to

overcome the abnormalities in heart
rhythm.
ØThis device uses electrical pulses
to prompt the heart to beat at a
normal rate
ØA pacemaker system consists of a
battery, a pulse generator,
electrodes and a lead wire
connecting the two
ØA pacemaker help monitor and control the heartbeat. The
electrodes detect heart’s electrical activity and send data through the
wires to the generator. If heart rhythm is abnormal, the generator will
send electrical pulses to heart. The pulses travel through the wires to
reach the heart.
ØThe pulse generator is encased in ASTM grade 1 titanium.
ØThe electrodes are made of platinum, silver, titanium, stainless steel
or cobalt alloys.
ØMost pacemakers use a lithium iodine battery
ØThe lead connector is injection molded of polyether urethane and
composed of polytetramethylene ether glycol and 1,4-butanediol.
ØThe lead must be durable, flexible, noncorrosive, and a good
electrical conductor
 Cardiopulmonary bypass
ØAlso known as extracorporeal circulation (or) heart lung machine

ØIt is a technique in which a machine temporarily takes over the

function of the heart and lungs during surgery, maintaining the
circulation of blood and the oxygen content of the patient

ØDeveloped in 1950 by Dr. Gibbons

ØCPB has enabled the extraordinary advances in open-heart surgery

ØCPB was operated by perfusionists

ØThe machine does the work of the heart (pump blood) and the
lungs (supply oxygen to red blood cells)

ØThe cardiopulmonary bypass (CPB) system is designed to pump

unoxygenated venous blood from the right side of the heart though a
synthetic oxygenator rather than through the lungs and return
oxygenated blood to the systematic arterial circulation.

ØHeart lung machine consists of three main functional units, the

pump, the oxygenator and heat exchanger, ventricular vent,
pericardial suction line, tubing, filters, and reservoirs
Components of heart-lung machine
ØCardioplegia
Heart-lung machine circuit consists of a separate circuit for infusing a
solution into the heart itself to produce cardioplegia to stop the heart
from beating, and to provide mycocardial protection (to prevent
death of heart tissue)

ØCannula
A venous cannula removes oxygen deprived blood from a patients
body. An arterial cannula is sewn into patients body to infuse oxygen-
rich blood. Cardioplegia cannula is sewn into the heart to deliver a
cardioplegia solution to cause the heart to stop beating
ØBlood reservoir
The blood reservoirs serves as a receiving chamber for venous return,
facilitates a venous bubble trap, provide a convenient place to add
drugs, fluids, or blood, and adds storage capacity for the perfusion
system.
Reservoirs may be rigid (hard) plastic or soft, collapsible plastic bags.

ØHeparin
A powerful anticoagulant, heparin should be given to the patient in
order to reduce the blood’s ability to clot, reducing the risk of clots
forming in the heart-lung machine.
ØPumping system
Roller pumps: Roller pumps consists of tubing's, which is compressed
by two rollers 180° apart. Forward flow is generated by the roller
compression and flow rate depends upon the diameter of the tubing,
rate of rotation
Excessive compression of the tubing increases the risk of hemolysis

ØCentrifugal pump
It consists of smooth plastic cones, which when rotated rapidly,
propel blood by centrifugal force.
ØOxygenators
Oxygenators not only supply vital oxygen for the blood, but also
transport carbon dioxide, anesthetics, and other gases into and out of
the circulation
There are two types of oxygenators
1) Bubble oxygenator
2) Membrane oxygenator
Bubble Oxygenators
ØIn bubble oxygenator venous blood drains directly into a chamber
into which oxygen is infused through a diffusion plate. The diffusion
plates produces thousands of small oxygen bubbles within blood. Gas
exchange occurs across a thin film at the blood-gas interface around
each bubble. Carbon dioxide diffuses into the bubble and oxygen
diffuses outward into blood.
Membrane Oxygenators
ØMembrane oxygenator imitate the natural lung by a thin membrane
of either micro porous polypropylene or silicone rubber between the
gas and blood phases.
ØOxygen enters from one end of
the bundles of hollow fibers and
exits at the opposite end. The
hollow fiber bundles are potted at
each end to separate the blood and
gas compartments. Oxygen and
carbon dioxide diffuse in opposite
directions across the aggregate
large surface of the hollow fibers
ØHeat exchanger
Control body temperature by heating or cooling blood passing
through the perfusion circuit.
In heat exchanger, blood flows through spiraling coils made of
stainless steel. The inner walls of the coils are coated with polymers
to limit-surface interactions (resin coated aluminum tubes).
ØHeart-lung machine used in surgical procedures
ü Coronary artery bypass surgery
ü Cardiac valve repair and/or replacement (aortic value, mitral valve,
tricuspid valve, pulmonic value)
ü Transplantation (heart transplantation, lung transplantation, heart-
lung transplantation)
ü Implantation of heart
ØOther materials used in various components of CPB systems
include polyester (mesh in filter), acrylonitrile-styrene polymers,
polurethane, polycarbonate, and stainless steel.

ØBecause no synthetic surface is completely thromboresistance,

systematic anticoagulation is a requirement of CPB device
 Nonthrombogenic treatments
ØThe initial event after a foreign material is exposed to the blood is
protein adsorption onto the surface, followed by a complicated
sequences of events, including activation of the intrinsic clotting
system, activation of platelets, thrombolysis, and activation of
complement system.
ØOver years, a substantial amount of research has been performed
to improve the biocompatibility of polymeric materials in contact
with blood.
ØHowever, the precise relationship between the nature of the
surface, blood compatibility, and the mechanism of surface-induced
thrombosis has not yet been completely elucidated.
ØMajor factors influencing blood interaction at polymer interfaces
are determined by the composition of the surface and the physical
and chemical properties that the surface may encounter within the
biological environment.
ØOne approach is to synthesize nonthrombogenic polymers with
surfaces tailored to minimize specific blood interactions, such as
thrombus formation and platelet interactions.
ØIt is generally accepted that a hydrophilic environment at the
blood-polymer interface is beneficial in reducing platelet adhesion
and thrombus formation.
ØModification of surface hydrophilicity was attempted using
albumin and poly(ethylene oxide)
ØBlood clotting and thrombus formation are controlled by a
naturally occurring polysaccharide drug, heparin.
ØThese drugs interact with the coagulation cascade (Factor Xa) and
prevent fibrin formation

ØFibrin molecules combine to form long firbin threads that entangle

platelets, gradually hardens and contracts to form the blood clot.
ØHeparin prevents thrombus
formation by binding to
antithrombin III (ATIII) and
catalyzing the action of ATIII to
neutralize thrombin, thereby
preventing the catalysis and
cleavage of fibrinogen to fibrin.
ØClinically, heparin is administered via subcutaneous or intravenous
administration for conditions such as deep vein thrombosis.
ØTo prevent thrombosis on the surfaces of vascular grafts, many
groups are investigating the incorporation of heparin directly with
the polymer surface. Therefore, the bioactivity of the polymer-
associated drug is essential for the successful design of
nonthromogenic materials.

Activated-partial thromboplastin time assay

ØThe bioactivity of heparin-containing polymers coated onto
surfaces can be measured using the activated-partial thromboplastin
times assay
ØThe heparinized polymers are coated onto glass beads, which
serves as a physical support and also as a means to increase the
surface area of the test sample.
ØThe heparinized polymer coated beads are incubated with platelet-
poor plasma and activated with thrombin at 37℃ for 2 min. A
calcium chloride solution is added, and the time for a clot formation
is measured with a mechanical endpoint fibrometer.
ØThe bioactivity of surface immobilized heparin is obtained by
comparing the APTT endpoints generated for surface-immobilized
heparin with heparin solutions of known concentrations.
 Heparin-containing bioactive surfaces

ØThere are several techniques available to utilize the anticoagulant

activity of heparin in conjunction with blood-contacting materials

1) heparin releasing surfaces

2) Heparin immobilized surfaces

3) Coating surfaces with copolymer of heparin

 Heparin releasing systems
ØHeparin-dispersed polymers release heparin primarily by diffusion
from the bulk polymer, through the surface of the material into the
blood stream.

ØHeparin dispersed systems were initially prepared by mixing

heparin with a hydrophobic polymer solution and casting to form the
device or applying as a coating onto another substrate material.

ØLimitations: prevents long term release, optimal control of

hydrophilic heparin release rates due to hydrophobic polymers and
the heterogeneity of heparin within the polymer matrix
ØHeparin is a highly negatively
charged polysaccharide led
researchers to bind heparin onto a
cationic surface through ionic
bonding
ØAn insoluble polyelectrolyte
complex was formed by combining
two water soluble polymers, poly
(allylamine) and heparin.
ØAn insoluble polyelectrolyte complex was formed by combining two water
soluble polymers, poly (allylamine) and heparin.
ØOn application of electric current, a rapid structural change of the complex
occurs, dissolving the polymer matrix in proportion to the intensity of the an
applied current.
ØThe disruption of ionic bonds in the polymer matrix attached to the cathode
and subsequent release of heparin was due to the locally increased pH near the
cathode from hydroxyl ion production
ØSurface erosion of the polymer matrix
Heparin immobilized onto polyurethane
ØThe main alternative to a heparin release
device is the covalent coupling of heparin
or other anticoagulant drugs directly onto
the polymer surface.
ØThis process maintains a constant
concentration of heparin on the surface to
interact with ATIII.
ØCompared to dispersed or ionic systems,
chemically coupled surfaces shows
thromboresistance for longer times than
the release systems.
ØHeparin was immobilized onto the
surface of Biomer (polyurethane) using
hydrophilic spacer groups, specially
PEO.

ØFirstly, coupling a telechelic

diisocyanate-derivatized PEO to biomer
through an allophanate-biuret reaction
(the reaction between isocyanate and
urethane NH or urea NH).

ØThe free isocyanate is then coupled

through condensation reaction to
function groups (-OH, -NH2) on heparin
HEP-PEO polymer coating
Dental implants
 Tooth replacements
ØNaturally occurring minerals/parts from dead animal were used to replace
damaged dentition

Ø Shaped to resemble lost region/ component

ØInterfacing of implant with tissue was ignored

ØExtended oral functions were observed in early tooth replacements

(evidenced by wear facets)

ØReplacement of tooth by semi-precious/ precious gemstones, gold, ivory,

bone etc.
 Progress of dental implants
ØMaterial concepts developed to answer concerns via systematic
investigations:
ü Physical

ü Mechanical

ü Chemical

ü Electrical

ü Biological

Ø Design and biomaterials

 Dental implants
ØEndosteal (Endosseous):
ü Enters the bone tissue
ü Root-forms (cylinders, screws, pleteaus), blades, staples, ramus frames
ØSubperiosteal:
ü Contacts the exterior bone surface
ü Fitted to bone surface as customized shapes
ü Bone plates placed onto bone under periosteum and fixed with endosteal screws
 Modern dental implants

ØEndosteal systems fabricated from:

ü Bent wires
ü Lost wax casting
ØBlade/plate: Treat edentulous spaced where thickness of bone is limited

ØTransosseous, staple, ramus frame: Treat fully edentulous mandible

Ø Endodontic stabilizers: Designed to pass through distal pump chamber
regions of endodontically treated teeth (high crown/root ratio)
 Subperiosteal system
ØCustom made devices for each patient

ØCast framework fitted to bone using initial working model obtained via
ü Surgical impression of bone
ü Computer assisted tomography (CAT)-scan image

ØCo-alloy/ Ti used as construction material

ØGeometric form, framework, and intraoreal denture connections have

changed over time.
 Issues in design
ØFormation of groups/ individuals propose design carrying their names

ØInterest in “solving it all” problems

ØBoth short and long term needs of patients with one design

ØReporting by some may be biased

ØPatient/ clinical/ company’s interest may not be separable.

 Materials

ØRoot form devices made from:

ü Gold, platinum, iridium, palladium

ØCost and strength:

ü Led to development of tantalum, titanium, zirconium, stellite (Co-
based alloys), stainless steel

ØWide range of alloys, ceramics, polymers, and composites

 Dental synthetic biomaterials
ØMetals & alloys:
ü Ti, Zr, Ta, Stellite, stainless steel

ØCeramics:
ü Al2O3, ZrO2, Glass, carbon, calcium phosphates

ØPolymers:
ü Polyethylene (PE), Poly tetrafluoroethylene (PTFE), polysulfone (PS),
polyethylene terephthalate (PET)
 Material exposure
ØDental implants contact:
ü Bone and soft tissue interfaces within submucosal region

ü Provide areas for mechanical stress transfer

ü Implant to tissue contact critical

ü Determines quality and stability of intraoral function

ü Implant connected to transmucosal/ transgingival post providing base

for dental bridge abutment
 Oral environment
ØDental implants percutaneous connection from intraoral to tissue sites
makes complex set of conditions

ü Oral activity: multi-variant external environment (food, abrasion, pH,

temperature, force, bacteria, etc.)

ü Requires seal between internal and external environment

ü But, oral tissues are very resistant to external environment

 Dental implant treatment
Ø Directly influences healing and restorative processes
ü Some devices stay for months prior to abutment attachment and
intraoral prosthesis

Ø Healing under no oral function (minimal mechanical force transfer)

ü Remodeling of bone along biomaterial surfaces to create interfaces
osseointegration
ü Bone is allowed to form along implant healing
 Endosseous dental implant systems
ØDirectly in contact with tissues:
Root forms:
ü Placed at anatomical positions where natural tooth roots had
previously existed

ü Resemble helical spirals, threads, cylinders, rods, pins, cones etc.

ü Ti-alloys, cobalt alloys, aluminum oxide, TiO2, ZrO2,, C, C-Si, polymers

(PMMA, PFTE, polysulfone, PDMS)

ü Available with calcium phosphate ceramic coating

 Endosseous dental implant systems
ØEndodontic stabilizers:
ü Are long pins or screws of small diameter to pass through a root canal

ü Placed at minimal bone and periodontal ligament support

ü Enhances tooth stability

ü A stable seal is required at the tooth root apex area

ü Ti-6Al-4V and Co-alloys, sapphire (aluminum oxide) ceramic

 Endosseous dental implant systems
ØBlades:

ü Used in special situation when patients have been edentulous for

extended periods

ü Applied to areas of bone resorption

ü Resemble knife blade/wedge

ü Ti-alloy, 316 SS, Co-alloys, ZrO2, Al2O3

 Endosseous dental implant systems
ØStaples/ frames:

ü Places in anterior region of mandible and protruded through gingiva

into oral cavity
ü Interconnecting two transosteal threaded pins
ü Ramus frames intended for treating endentulous mandibular arch

ØPlates/ screws/ wires:

ü Used in oral and maxillofacial surgery

ü Stabilize craniofacial bone lesions
 Subperiosteal implants
ØPlaces along bone surfaces under periosteum

ØCast to specifically fit each patient’s bone structure

ØMade of polysulphide, polyether, silicone from radiographic/ serial tomogram

ØCo, Ti alloys
 Subperiosteal implants
ØMucosal inserts:
ü Mushroom shaped buttons with protrude from denture surface

ü Penetrate into adjacent mucosa, and epithelial cells crypt around

during healing

ü Placed onto freshly prepared soft-tissue lesions

ü 316 SS, Ti, Al2O3 ceramic

ü Denture base: PMMA

 Others
ØCrown bridge/ denture restorations:
ü Mechanically/ chemically attached to dental implants and become part
of overall restorative treatment

ØFixed restorations:
ü Root-form and blade rigidly attach the intraoreal prosthesis
ü Galvanic coupling of dissimilar alloys, casting defects, high carbon
content: influence device longevity
 Tissue interface
ØOcclusal forces dissipate through associated tissues

ØInterface stability over time decides quality and functional stability

ØInterfacial conditions:
ü Fibrosteal integration: fibrous tissue interfaces around endosteal
portion of implant
ü Osteointegration: direct bone to biomaterial interface without fibrous
tissue for greater force transfer
Orthopedic implants
ØBiological environment should not get adversely affected by
implant material

ØMaterial itself should not get affected by surrounding host tissues

and fluids

ü Understanding correlation between structure and properties

of natural tissues those are being replaced

ü To meet specific orthopedic need rendered by tissues

(function-structure relation)
 Calcified tissues

ü Collagen: Protein component

ü Other organic phases

ü Inorganic component of hydroxyapatite

ü Organization of these two main components is essential

for characterizing bone structure
 Compact cortical bone
ØFour levels of hierarchy:

ü Collagen triple helical structure (tropocollagen) and OHAp

(hydroxyapatite) from basic molecular construct

ü Collagen-Hap organization

ü Fibrillar composite, fiber, fiber-bundles Lamellar type

structure

ü Lamellar units form secondary osteons or Haversian systems

bone tissue structure
 Hydroxyapatite
ØHexagonal unit cell with space group P63/m

ØA = 9.88Å and c = 6.418 Å

ØContains two molecular units of Ca5(PO4)3OH

ØSmall crystallite size (2 x 20 x 40 nm)

ØX-ray diffraction of bone shows considerable line broadening

ü Makes identification of additional phases difficult

ü Has helped developing Ca-based bioceramics

 Collagen triple helix
ØAmino acids polypeptides Protenis

ØAlpha chains coil to form tropocollagen

 Hap- Collagen organization
ØCollagen and hydroxyapatite Arrangement controlled by
bonding at molecular level

ØCollagen structure changes during formation results inferior

physical properties of bone (observed via bone pathology)

ØHAp observed both intra- and inter-fibrillary with collagen

ØCan model elastic properties weighed by their volume

 Lamellae type structure
ØFibrillar composites form fiber and fiber bundles

ØGet layered as lamellar type units

ü Circular lamellar units forming secondary osteons or Haversian
systems (in mature human bone)
ü Straight lamellar units forming plexiform bone (observed in
young quadruped animals)
ü Composite analysis to model elastic properties of tissue can
render macroscopic properties of bone
 Multiscale hierarchy
ØStiffness composite structure of mineral microcrystals and protein (principally
collagen) fibers
ØSlow creep results from slip at cement lines between osteons
ØToughness cement lines as weak interfaces
ØLacunae (ellipsoidal pores) provide space for the osteocytes, the living cells of bone
ØBone cells at this level of scale permit bone tissue to remodel its structure in
response to prevailing stresses
ØHaversian canals (cylindrical pores) contain blood vessels for nourishing tissues
ØCanaliculi (fine channels) radiating from the lacunae mechanical stress in bone due
to physical activity is considered to be important in pumping nutrients through these
channels
ØPore structure of bone essential in maintaining its viability and consequently its
ability to adapt to mechanical stress
 Elastic properties of bone
ØBone is viscoelastic

ØElastic properties elicit light on understanding the performance of

bone

ØQuasi-static strain: stress-strain curve, young’s modulus, poisson’s

ratio, yield stress, fracture stress

ØElastic/plastic strain: Tension, compression, torsion, shear, and

fatigue
 Elastic constants of bone
ØThere exists profound relationship between microstructure and its
mechanical properties

ØBone is
ü Either transverse isotropic (hexagonal symmetry) requiring six
elastic compliance or stiffness to describe its elastic properties

ü Or orthotropic (orthorhobic) requiring nine such constants

ü Helps understanding the resorption and remodeling at bone-

implant interface
ØGeneral hookes law:
!ij=cijkl"kl
ØWhere !ij and "kl are the stress and strain tensors
ØCijkl is the fourth rank elastic stiffness coefficients
transverse isotropic orthotropic

C22 C23
C23

C55

ØIn cases where bone resorption leads to porosity, there is a gradient

in the structure so that measurement of properties in the radial and
tangential directions are significantly different.
 Viscoelastic properties of bone
ØNo time-temperature superposition to obtain its properties
(non linear and thermorheologically complex)

ØKelvin Voigt model: Portrays creep

ØMaxwell model: stress relaxation

ØThree element model: better representation of actual

system
ØMetals: Biomaterials
ü Load bearing
ü 316L, Co-Cr, Ti-6Al-4V

Ø Total hip arthroplasty

Ø Introduced by orthopedic surgeon john charnley in 1982.

Ø Metal femoral prosthesis held in place by PMMA with acetabulum

made of UHMWPE also cemented with PMMA

Ø Not to be corrosive, mutagenic or carcinogenic within the body

Ø Porous outer coatings

ØPolymers:

ü Articulating surfaces in joint prosthesis

ü Low coefficient of friction

ü Low wear rate in contact with opposing surfaces

ü Poor creep and stress corrosion

ü UHMWPE: ultimate choice

ü PLA/PGA : Biodegradable polymers

ØCeramics & glasses:
ü Resistance to oxidation

ü High stiffness

ü Low friction and wear

ü Requires small grain size

ü Provide an interface of biological compatibility with

osteoblasts

ü Bioglass, hydroxyapatite + bioinert Al2O3, ZrO2

Adhesives and sealants
ØAdhesion: The state at which two surfaces are held together by interfacial
forces, which may consist of all known chemical attractive forces, as well as
mechanical working action or both.
ØAdhesive is a substance capable of holding materials together by surface
attachment.
ØSealant: A material applied to a joint in paste or liquid form that hardens or
cures in place, forming a barrier against gas or liquid entry.
ØThe bond that resists separation is formed between the substrates or
surfaces comprising the joint and work is required to separate them.
ØThe term adhesive covers the designation as cement, glue, paste, fixative and
bonding agent in various areas of adhesive technology.
ØCommercial adhesive systems are often designed to result in only a thin layer
adhesive for efficient bonding of the two surfaces since thick layers may contain
weakening defects such as air voids or contaminations.
 Adhesives and Sealants-Biomaterials?
• Join components of medical devices-Mechanical
fastening;
• Prevent corrosion;
• Resist fatigue;
• Fill space – smooth contours-joining prosthesis to
bone;
• Wound sealing & closure
ØThe application of adhesive biomaterials range from soft tissue adhesives
used both externally (temporarily fix adjunct devices such as colostomy bags)
and internally ( for wound closure and sealing, to hard tissue adhesives used to
bond prosthetic materials to teeth and bone on permanent basis)

ØDue to hostile biological environment, major problem in the formulation of

medical and dental adhesives is to develop a material that will be easy to
manipulate, interact intimately with the tissue to form a strong bond, and also
be biocompatible.

ØOver past two decades, more success at a clinical level has been achieved in
bonding to hard tissues than to soft tissues.
ØWound closure by means of sutures extended back many centuries
ØThe idea of using adhesive is more recent
ØHide glue is similar to gelatin, which itself derived from collagen.
ØOther biological adhesives such as blood and egg white have also been
known for centuries
ØNatural materials such as cross-linked gelatin and thrombin-plasma were
investigated with a major stimulus of 2-cyanoacrylate
ØThe clear liquid and its higher homologs (ethyl, butyl, etc.) were found to
polymerize rapidly in the presence of moisture or blood, giving rapid
hemostasis and highly adherent films.
ØThe first glue developed was methyl cyanoacrylate, which was studied
extensively for medical applications and was rejected due to its potential tissue
toxicity such as inflammation or local foreign body reactions. Methyl alcohol
has a short molecular chain which contributed to these complications
ØBy changing the type of alcohol in the compound to one with a longer
molecular chain, the tissue toxicity is much reduced. All the medical grade
tissue adhesives currently available for human use contain butyl-esters.
ØFixation of orthopedic joint components by a cement dates from 1891.
ØThese involves bonding by mechanical interlocking into surface irregularities.
ØIn case of tooth restorations, leakage along the bonded interface develops
ØThis micro-leakage led to an intensive effort to develop adhesive dental
cements and filling materials.
ØBonding materials and techniques are now a major component of clinical
dentistry.
ØEffective clinical bonding of polymerizable fluid dimethacrylate monomers and
composite formulations to dental enamel, has been achieved by using
phosphoric acid etching (acid-etch technique) of the surface.
ØThe fundamental aspects of the formation of adhesive bonds at interfaces are
not yet fully understood even though successful application of adhesives in
technically demanding situations has been achieved.
ØExperience and theory have shown that severe hostile environments such as
biological environment may require specific surface pretreatments (cleaning or
etching process) for the surfaces being joined to achieve intimate interfacial
contact between the bonding agent and the adherends.

ØHowever, the design factors of the adhesive joints, applied loads, and the service
environment will affect the mechanical performance and life expectancy.

ØTo achieve intimate molecular contact between the adhesive and the adherend,
the adhesive/primer should
1) Exhibit a zero or near zero contact angle
2) Have a low viscosity during bonding
3) Be able to displace air and contaminants during application.
ØFour main mechanisms of adhesion at the molecular level have been proposed
1. Mechanical interlocking (penetration of the bonding agents into surface
irregularities or porosity in the substrate surface)
2. Adsorption (van der waals and hydrogen bonds)
3. Diffusion theory (diffusion of polymer molecules across the interface)
4. Electronic theory (electronic transfer may lead to electrostatic forces that
result in high intrinsic adhesion)
Soft tissue adhesives
ØMost soft tissues are temporary (removed or degrade when wound healing is
advanced)

ØEffective adhesion can be obtained on dry skin or wound surfaces by using

wound dressing strips with acrylate based adhesives.

ØOn wet wound surfaces, the adhesive must be easily spread, provide adequate
working time, develop and maintain adhesion, provide hemostasis, facilitate
wound healing, and maintain biocompatibility.

ØCurrent systems in clinical use: cyanoacrylate esters, fibrin sealants, gelatin-

resorcinol-formaldehyde glue, bioadhesives.
Cyanoacrylate esters
ØThese esters are fluid, water-white monomers that polymerize rapidly by an
anionic mechanism in the presence of weak bases such as water or NH2 groups.
ØThe degradation rate is also slow (several weeks)
ØThese materials achieve rapid hemostasis as well as a strong bond to tissue
ØHowever, the polymer film is little brittle and can be dislodged on mobile
tissue, and the material is difficult to apply on large wounds.
ØBecause of adverse tissue response and production of tumors, these are not
approved in USA but n-butyl cyanoacrylate is approved by several other countries
ØThe current uses are as a surface wound dressing in dental surgery, especially
in periodontics, and in life threatening applications such as brain arteriovenous
malformations.
Fibrin sealants
ØFibrin sealant involve the production of a synthetic fibrin clot as an adhesive
and wound covering agent
ØBy mixing fibrinogen and aprotinin, fibrin clot occurs
ØFibrin sealant has four main advantages
1. Hemostatic
2. Adheres to connective tissue
3. It promotes wound healing
4. It is biodegradable
Ø The adhesive strength is not as high as cyanoacrylates
Ø Complications: formation of antibodies and thrombin inhibitor.
Gelatin-resorcinol-formaldehyde glue
ØThis glue is less toxic compared to methyl cyanoacrylate.

ØIt is fabricated by warming 3:1 mixture of gelatin and resorcinol and adding an
18% formaldehyde solution. Cross linking takes place in 30 sec.

ØIt is used in variety of soft tissue applications but technical problems and
toxicity have limited its application in aortic dissection
Bioadhesives
ØBioadhesives are involved in cell to cell adhesion (adhesion between living and
nonliving organism, and adhesion between an organism and foreign surfaces)

ØAdhesives produced by marine organisms such as barnacle and the mussel are
extensively investigated.

ØThese organisms secrete a liquid acidic protein adhesive that is cross-linked by

a simultaneously secreted enzyme system. The bonding involves hydrogen and
ionic bonding from the acidic groups.
Hard tissue adhesives
ØProstheses can be attached to calcified tissues (bone, teeth enamel, etc) by
mechanical interlocking
ØThus, room temperature polymerizion of methyl methacrylate systems are used
to fix orthopedic implants and for dental restorations
ØSince conditions are more stringent in the mouth, a new dental cements and
adhesive systems has occurred to provide a leak proof bond to attach fillings,
crown etc.
ØDental cements are fast setting pastes obtained by mixing solid-liquid
components.
ØZinc phosphate cement is the traditional standard. Zinc oxide power and 50%
phosphoric acid solution containing Al and Zn is mixed to form amorphous zinc
phosphate binder.
ØThis cement can gradually dissolve in oral fluid and can irritate pulp
ØPolycarboxylic acid cements were developed in 1968.
ØFrom zinc oxide and polyacrylic acid solution zinc polyacrylate cements is
formed
ØThe metal ion cross links the polymer structure via carboxyl groups, and the
carboxyl groups form a complex to Ca ions in the surface of the tissues.
ØZinc polycarboxylate cements have adequate physical properties, excellent
biocompatibility and proven adhesion to enamel and dentin.

ØGlass ionomer cements are also based on polyacrylic acid but utilize calcium
aluminosilicate glass powder instead of zinc oxide.

ØResin cements are fluid or paste like monomer systems based on aromatic or
urethane dimethacrylates
Ophthalmologic applications
Light that penetrates into
the eye is partially
refracted in the cornea,
passes through the
aqueous humor and the
pupil, is further refracted in
the crystalline lens, passes
through the vitreous
humor, and converges on
the retina
Ø Diverse polymeric devices, such as spectacles, contact
lenses, and intraocular implants, are used to correct the
optical function of the eye.
Contact lenses
Ø Contact lenses are optical devices that must have good
transmission of visible light.
Ø Pigments and dyes are added to some contact lenses for
cosmetic effect.
Ø Contact lenses also have UV light absorbing additives,
usually copolymerized in the contact lens material, to
protect the eye from the harmful effects of UV light
Properties required in contact lens materials

Ø Optical properties
Ø Chemical stability
Ø Reasonable cost
Ø High oxygen transmissibility (to meet metabolic
requirements of the cornea)
Ø Tear film wettability (for comfort)
Ø Resistance to accumulation on the lens surface
Ø Most of the available contact lenses were developed with
good oxygen permeability
Ø For a contact lens, its oxygen transmissibility (Dk/L) is more
important than its permeability (P)
P= oxygen permeability coefficient
D= diffusivity
K= Henry’s law solubility coefficient
L=Average thickness of the lens
Ø Oxygen transmissibility is defined as oxygen permeability
coefficient of the material divided by average thickness of
the lens
Ø For oxygen permeability, the contact lens is made of
poly(dimethyl siloxane)
Ø Because of its hydrophobic character, a silicone rubber lens
must be treated in an RF-plasma reactor or other suitable
procedure to make its surface hydrophilic and tolerated on
the eye.
Ø Silicone rubber lenses are not been very successful for
general cosmetic use, not only because of surface problems
and comfort, but also due to the strong tendency to adhere
to the cornea.
Ø Now, there are variety of materials with diverse physical
properties
Soft hydrogel contact lenses

Ø Soft hydrogel contact lenses are flexible and fit snugly on the
corneal surface
Ø Since there is little tear exchange under these lenses, most
of the oxygen that reaches the cornea must permeate
through the lens.
Ø The oxygen permeability coefficient of hydrogel materials
increases exponentially with the water content
Ø These hydrogels are made of slightly cross-linked hydrophilic
polymers and copolymers.
Ø The original hydrogel contact lens material was poly(2-
hydroxyethyl methacrylate); at equilibrium swelling in
physiological saline solution, it contains 40% water of
hydration.
Ø The oxygen transmissibility of the thick PHEMA hydrogel
contact lenses was found to be insufficient for normal
corneal metabolism.
Ø New ultrathin hydrogels were fabricated with higher water
content or with water content similar to PHEMA
Ø Other hydrogel contact lens materials include HEMA
copolymers with other monomers such as methacrylic acid,
acetone acrylamide, and vinyl pyrrolidone
Ø U.S Food and Drug Administration classified Hydrogel lenses into
four general groups:
1. Low water (< 50%) and nonionic
2. High water (> 50%) and nonionic
3. Low water and ionic
4. High water and ionic
Ø The ionic characteristics is usually due to the presence of
methacrylic acid, which is responsible for higher surface protein
binding to the contact lenses
Ø Higher water for hydration is a desirable property for good oxygen
permeability, but it has some disadvantages such as friability and
protein penetration into the polymer network.
Ø Physiologically and optically, ultrathin low-water content lense
perform very well as daily wear lenses
Ø With temperature changes and water evaporation, all hydrogel
contact lenses dehydrate to some extent
Ø High water content lenses dehydrate more than low water content
lens
Ø Thin lens dehydrate more easily compare to thick lens
Ø A drawback with high water content, thin hydrogel contact lenses is
that as they degrade on the eye, they induce corneal epithelium
injuries by a mechanism which is not clear.
Ø Therefore, ideal hydrogel contact lens would be ultrathin, resistant
to mechanical damage, made of nonionic polymer and retain a
high water content (> 70%) on the eye
Flexible fluoropolymer lenses (FFP)
Ø FFP lens was made from a copolymer of a telechelic
perfluoropolyether (which imparts high oxygen
permeability) with vinyl pyrrolidone (imparts wettability).

Ø This flexible, non hydrated contact lens is made by molding

procedure.

Ø It has high oxygen permeability, owing to its high fluorine

content it is more resistant to coating by tear protein than
other contact lens materials
Rigid contact lenses
Ø Rigid contact lenses and FFP lenses, fit loosely on the cornea and
move with the blink over the tear film
Ø The mechanical properties of rigid and FFP must be such that any
flex on the lens must recover instantaneously at the end of the
blink.
Ø Rigid gas-permeable (RGP) contact lenses are copolymers of methyl
methacrylate with siloxanyalkyl methacrylates.
Ø To compensate for the hydrophobic character by the high siloxane
content, the copolymer should contain some hydrophilic character.
Ø Most commonly used hydrophilic comonomer in rigid lenses is
methacrylic acid.
Corneal implants
Ø The cornea is an avascular tissue that consists of three principal
layers.
Ø The outermost layer (five cellular layers) is epithelium
Ø The central and main portion of the cornea is the stroma, a
collagenous connective tissue that is 78% hydrated in its normal
state.
Ø The endothelium is the inner most monocellular layer, is responsible
for corneal hydration
Ø Normal corneal hydration is disrupted by injury to the epithelial and
endothelial membranes
Ø Swelling, tissue proliferation and vascularization may compromise
the transparency of the cornea.
Ø There are several types of corneal implants that replace all or part of
the cornea.

Epikeratophakia and Artificial epithellum

Ø To correct the optics of the eye after cataract extraction, the surgeon
perform and epikeratophakia procedure which consists of
transplanting a slice of donor cornea.
Ø The transplanted tissue heals into a groove carved into the recipient
corneal surface and is reepithelialized with the recipient corneal
epithelium.
Ø A modification of this technique with artificial material showed
almost similar results
Ø An epithelium that has become
irregular through swelling and
proliferation has been replaced by an
artificial epithelium made of hard
plastic contact lens glued with a
cyanoacrylate adhesive to the corneal
storma.
Ø This is not successful because of
failure of glue to maintain a tight
attachment of the prosthesis to the
corneal stroma and also because of
the epithelial penetration between
the prosthesis and the cornea
Artificial corneas
Ø Corneal transplants from donor eyes are usually highly successful.
Ø In the rare instance of transplant failure, an opaque cornea can be
replaced with an artificial cornea
Ø These are through and through corneal implants, consisting of a
central optical portion and some modality of skirt that fixes the
prosthesis to the recipient cornea
Artificial corneas
Ø The main problem with this implants are, they are not fully buried in
the recipient tissue: faulty tissue –prosthesis interface, epithelium
downgrowth, tissue ulceration and infection around the prosthesis

Ø The feasible solution would be development of a material for the

optical portion of the keratoprosthesis that would accept growth and
attachment of transparent epithelium on its surface

Ø Select suitable biomaterials that would heal into the recipient

corneal tissue
Intracorneal implants
Ø Mostly Intracorneal implants are made of hydrogel materials tailored to have
permeability to metabolites and able to correct severe myopia.
Ø The stromal cells and the epithelium receive their
nutrients from the aqueous humor and also release
waste products in the same direction.
Ø Therefore, some previous intrastromal implants such
as PMMA and Polysulfone, which are impermeable to
metabolites, result in ulceration and vascularization.
Ø Recently, instrastromal ring made of PMMA or
silicone rubber can change the corneal curvature and
hence the eye’s optical power.
Ø These rings can make corneal curvature steeper,
increasing/decreasing the refractive power, or flatter.
Intraocular lens implants
Ø Intraocular lens (IOL) are used after cataract extraction to replace the opaque
crystalline lens of the eye
Ø A large variety of IOL designs and shapes are available
Ø The requirement of IOL materials are good optical properties and
biocompatibility with the surrounding tissues.
Ø Most IOLs are made of PMMA and the haptics are often made of the same
materials or polypropylene fiber
Ø UV absorbing material should be present in IOL to
protect the retina
Ø Soft IOLs are made of HEMA or other hydrogels
Ø Flexible IOLs are made of silicone rubber and alkyl
acrylate copolymers
Drug Delivery Systems
Ø Drug delivery is the method or process of administering pharmaceutical
compound to achieve a therapeutic effect in human or animals

Ø The blood plasma level rapidly increases and then exponentially decays as the
drug is excreted and/or metabolized.

Ø If the released concentration is above the permitted limit then it produces

undesirable side effects

Ø If the released concentration is less than

required limit then it is not of therapeutically
effective

Ø Therefore developing systems that release drugs in a controlled manner is

highly advantageous
 Diffusion controlled delivery system
Ø Two different devices are available in which the rate of drug release is controlled
by diffusion
1) Monolithic devices (diffusion through polymer)
2) Membrane-controlled devices (diffusion through membrane)
Monolithic device
Ø In monolithic device, the therapeutic agent is dispersed in a polymer matrix
and its release is controlled by diffusion from the matrix.
Ø Mathematical treatment of diffusion depends on solubility of the agent in the
polymer and two cases must be considered
Ø In one case, the agent is present below the solubility limit and is dissolved in
the polymer
Ø In the other case, the agent is present well above its solubility limit and is
dispersed in the polymer
Ø The release of an agent that is dissolved in the polymer can be calculated by
two equations

Early-time approximation, is valid for first

60% of release time

Late-time approximation

Thickness of the slab/polymer = l

Diffusion coefficient = D
Total amount of agent dissolved in the polymer = Mx
Amount released at time t =Mt
Ø When the agent is dispersed in the
polymer, release kinetics can be
calculated by Higuchi equation

A= slab area
Cs = solubility of agent in the matrix
Co =total concentration of dissolved and
Dispersed agent in the matrix

Ø Release rate decreases as the square

root of time over the major portion
of the delivery time
Membrane controlled device
Ø In this particular delivery system, the active agents is contained in a core that
is surrounded by a thin polymer membrane and release to the surrounding
environment occurs by diffusion through the rate-limiting membrane
Ø When the membrane is nonporous, diffusion can be calculated by Fick’s law
Ø If the membrane have well defined pores we have consider this porosity and
tortuosity in the ficks law
Ø Decision as to which type of device is most appropriate for an intended
application must consider the need for constant drug release, manufacturing
cost and safety.
Ø Long term zero order drug release is achievable with membrane controlled
devices but it is expensive

Ø The Ocusert therapeutic system is a flat, flexible, elliptical device designed

to be placed in the inferior cul-de-sac between the sclera and the eyelid and
to release Pilocarpine continuously at a steady rate for 7 days.
Transdermal applications
 Water penetration controlled systems

Ø In this type, the rate of delivery is controlled by the penetration of

water into the device.

Ø Two general types of devices are in use

1) Osmotically controlled devices

2) Swelling controlled devices

Osmotically controlled devices
Ø The osmotic agent is contained within a rigid housing and is separated from the
agent by a movable partition.
Ø One wall of the rigid housing is a semi permeable membrane and when the
device is placed in an aqueous environment, water is osmotically driven across
the membrane
Ø The resultant increase in volume
with in the osmotic compartment
exerts pressure on the movable
partition, which then forces the
agent out of the device through
the delivery orifice
Swelling controlled devices
Ø In this type of delivery system, the agent is dispersed in a hydrophilic polymer
that is glassy in dehydrated state but swells when placed in aqueous
environment.
Ø Since the diffusion of molecules in a glassy matrix extremely slow, no release
occurs while the polymer is in the glassy state.
Ø However, when such material is placed in an aqueous environment, water will
penetrate the matrix and as a consequence of swelling, the glass transition
temperature of the polymer is lowered below the temperature of the
environment and the drug diffuse from the polymer
Chemically controlled systems Hydrolysis/
enzyme
activity
Regulated systems
Ø Significant improvement can be realized if systems could be devised that are
capable of adjusting drug output in response to physiological need

Ø Regulated systems ca ne be broadly grouped into two types

1) Externally regulated devices (can alter the drug output only in response to an
external intervention)

2) Self-regulated devices (no need of external intervention)

Externally regulated systems
Ø Mechanical pumps that dispense drugs from a reservoir to the body by
means of catheter.

Ø Such pumps can be worn externally or can be implanted in a suitable body

site

Ø A major application is control of diabetes by delivering insulin in response to

blood glucose levels.

Ø Number of such pumps, such as CPI Lilly pump, have sophisticated control
mechanisms and microprocessors that allow programmed insulin delivery
Ø Another means of externally regulating drug delivery is by means of
magnetism.

Ø Small magnetic spheres are embedded within a polymer matrix that contains
a dispersed therapeutic agent.

Ø When an oscillating magnetic field is applied to the polymer, the normal

diffusional release is significantly increased
Self regulated systems
Ø Self-regulated devices are capable of altering drug output in response to an
external change
SUTURES
Ø Approximately 250 million sutures are used in USA annually
for a variety of surgical procedures from routine skin
lacerations to delicate organ transplants

Ø A suture is a complicated medical product that must be

designed and manufactured consistently to meet a range of
physical and chemical demands.

Ø The main function of the suture is to bring and hold tissue

together.

Ø Sutures are broadly classified according to the type of

material (natural or synthetic) from which they are made,
the permanence of the material (absorbable or
nonabsorbable) and the construction process (braided or
monofilament) used.
Regardless of material or its permanence, the suture must meet the strength
requirements necessary to close a wound under a given clinical circumstance.
BURN DRESSING
Ø A burn occurs when heat, chemicals, sunlight, electricity or radiation
damage skin tissues.

Ø Every year approximately 12,000 people die from severe burns and
thermal injury. Most of these deaths are due to catastrophic
problems that ensure when the skin’s integrity is disrupted.

Ø There are four different degrees of burning

Ø The major lethal problems are massive fluid losses and microbial
invasion.
Ø The best coverage for the wound is natural skin taken from the individual
himself (autograft) to avoid specific immunological incompatibility.

Ø If the burn injury is 35 to 50% of the total surface of the body, it is

possible to transplant partial thickness skin grafts from other non injured
areas of the patient.

Ø These grafts are usually about 0.3 to 0.5 mm thick and include the
epidermal layer and a thin portion of the underlying dermis.

Ø The donor site epidermis regenerates in 2-3 weeks from the basilar
epidermal elements left behind

Ø By simple diffusion of the nutrients for 72 hr or until neovascularization,

the grafts granulates the wound beds
Ø For burns more than 50% of the body surface area, obtaining enough
autograft becomes difficult.
Ø Using skin grafts from cadavers (allograft) helps
Ø Allografts may be used fresh, stores in glycerol at 4 °C, or preserved with
glutaraldehyde.
Ø Glutaraldehyde preservation eliminates the problems associated
sensitivity to foreign tissue, it kills all the cells of the allograft and
eliminates many of their advantages such as neovascularization from the
wound bed.
Ø Shortage of donors
Ø Porcine xenograft have been used after preservation but problems with
storage as well as limited biocompatibility restrict their usefulness.
Ø It is important to know that all natural grafts other than autografts must
eventually be replaced with the patient’s own skin
Ø A burn occurs when heat, chemicals, sunlight, electricity or radiation
damage skin tissues.

Ø Every year approximately 12,000 people die from severe burns and
thermal injury. Most of these deaths are due to catastrophic
problems that ensure when the skin’s integrity is disrupted.

Ø There are four different degrees of burning

Ø The major lethal problems are massive fluid losses and microbial
invasion.
Ø Many times the graft is meshed, which involves making small linear
incisions in the graft with a tanner mesher so that it may be
expanded in size.
Ø Mesh allows fluids to drain from the
bed, which helps to increase the
likelihood of graft survival.

Ø Mesh pattern is usually visible for

extended periods of time after
healing because the dermis does not
properly regenerate within interstices
 Design criteria for wound coverage
Ø Wetting the wound bed and adherence

Ø Porosity of the graft

Ø Dimensions of the graft (pore size and thickness)

Ø Strength of the graft

Ø Biodegradation rate

Ø Lack of antigenicity
 Macrostructure

Ø One of the functions of a wound cover is to provide a structural framework

for the healing wound.

Ø If this structure is not present, fibroblastic tissues will lay down collagen in a
random fashion, resulting in disordered dermis (scars)

Ø By providing scaffolding for the new vascular and mesenchymal tissue, an

orderly and controlled restructuring of the dermis can take place without
scar formation
 Selection of materials
Ø Common materials such as poly(dimenthyl siloxane) are unfortunately neither
hydrophilic nor biodegradable
Ø Polyamides such as hexamethylene adipamid and saturated polyesters such as
poly(ethylene terephthalate) are weakly hydrophilic and not biodegradable
Ø Poly 2-hydroxyethyl methacrylate is a relatively hydrophilic polymer but is also
not biodegradable
Ø Other compounds that are biodegradable and wet the surface, such as poly-n-
butyl-⍺-cyanoacrylate, have toxic by-products when they are broken down.
Ø Polypeptide polymers and certain polysaccharide compounds have the
advantage of being degraded by extracellular enzymes and yield non-toxic by-
products.
Ø Collagen is a polypeptide compound, hydrophilic in nature, and subject to
degradation by extracellular enzymes. It is weak antigen, with rejection
potential
 Selection of materials
Ø Collagen is extensively studied for strain viscoelastic properties and the rate
of degradation
Ø A problem noted with collagen was that by increasing the cross-linking the
compound became stiff and brittle. This could be overcome by incorporating
a second macromolecules, a glycosaminoglycan (GAG) into the membrane.
Ø For artificial skin, this GAG was chosen because
1. Low antigenicity
2. Non toxic breakdown products
3. Ability to decrease the rate of collagen breakdown
4. Ability to increase the strength of collagens while
making them more elastic
Ø The pore size is controlled by adjusting the collagen-GAG mixture.
 Natural graft materials
Ø Properties of natural autografts and some allografts include a decrease in the
quantity of bacteria in the wetted surface of the wound, a decrease in the
loss of fluids and proteins, a limiting effect upon wound contracture when
the dermal layer is included in the graft, a decrease in pain in second-degree
burns, and an increase in the neovascularization of the wound area.

Ø Major disadvantage of natural graft materials is

1. Lack of autograft in severely burned patients,
2. difficulty with storage of allograft materials,
3. antigenicity,
4. leading to the need for eventual replacement
5. potential to transmit diseases
Ø Xenografts, especially derived from porcine are used as a temporary wound
closure material
Ø The grafting success rate is lower than with fresh allograft and sterility of the
xenografts must be ensured to protect the already immunocompromised
burn patients.
Ø Amnion has been tried as a temporary natural wound dressing, but the
source must be carefully screened for disease.
Ø Amnion is freely available from the delivery of babies, and is relatively
inexpensive to prepare
Ø The adherence of amnion to wound is less successful
 Synthetic graft materials
Single laminar grafts
Ø In order to provide a simple method of closure, a number of simple, single-
layer, polymer wound dressings have been developed
Ø Ivalon sponge was developed in 1962
Ø The bacteria present under the graft wound spread into deep structures
when the sponge was used on third-degree burns.
Ø The brittle nature of the material, led to breakage into small pieces when the
graft was removed, leading to foreign body reactions within the ultimately
healed wound.
Ø Spray-on materials, such as hydroxyvinylchloride-acetate and sebacic acid
copolymer, produce the same problems of suppurative bacterial spread when
placed over open third degree wound.
Ø If the film is nonpermeable to moisture, accumulation of serous exudate and
suppurative material will result in uneven adhesion of the film to the wound
 Synthetic graft materials
Single laminar grafts
Ø A liquid gel made from agar and acrylamide copolymer has been developed
Ø This is used as a temporary cover because of its lack of adherence to the
wound and its fragile nature.
Ø Some advantages of the gel is that allows fluid to freely drain from the
wound without accumulating and because the material is highly translucent,
it allows easy inspection of the wound.
Multilaminar grafts
Ø In order to both control the ingrowth of fibroblasts and long term adhesion
to the wound, a large pore size must be maintained.
Ø Water permeability is necessary to prevent the wound from drying out
require a smaller pore diameter.
Ø The best approach to date is to create a bilaminar membranes
 Synthetic graft materials
Ø This approach makes designing the wound dressing simpler because
differences in physical strength, adhesion, pliability and other properties can
be separated between the two layers of the device.
Bioelectrodes
Ø The term bioelectrode denotes a class of devices which transmit
information into or out of the body as an electrical signal.
Ø Those transmit information out of the body generally comprise a
category of electrodes called biosensors
Ø Ex: sensors for oxygen, glucose, and urea, etc
Ø Bioelectrodes transmit information into the body are found in
electrical stimulation devices. EX: Pacemakers, transcutaneous
electronic nerve stimulators for pain suppression, cochlear
implantation etc.