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Dr. Alagiriswamy A A, (M.Sc, PhD, PDF)Asst. Professor (Sr. Grade),

Dept. of Physics, SRM-University,Kattankulathur campus,

Chennai

UNIT III

Lecture 4

ABCs of Biomaterials

Metals

Semiconductor Materials

Ceramics

Polymers

Synthetic BIOMATERIALS

Orthopedic screws/fixation

Dental Implants

Dental Implants

Heart valves

Bone replacements

BiosensorsImplantable Microelectrodes

Skin/cartilage

Drug Delivery Devices

Ocular implants

Changing the chemistry at the surface

Inducing roughness/porosity at the surface

Incorporate surface reactive materials (bioresorbable; helps in slow replacement by tissue)

Should not secrete oxidizing agents

Reduce corrosion rate of biomaterials

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Biological responses ; requirements

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CLASSIFICATION OF BIOMATERIALS

Biomaterials can be divided into three major classes of materials:

Metals

Polymers

Ceramics (including carbons, glass ceramics, and glasses).

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First Generation Implants

“ad hoc” implants

specified by physicians using common and borrowed materials

most successes were accidental rather than by design

Examples — First Generation Implants

• gold fillings, wooden teeth, PMMA dental prosthesis

• steel, gold, ivory, etc., bone plates

• glass eyes and other body parts

• dacron and parachute cloth vascular implants

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METALLIC IMPLANT MATERIALS

Stainless steel

Cobalt-chromium alloys

Titanium alloys

Metallic implants are used for two primary purposes.

To replace a portion of the body such as joints, long bones and skull plates

Fixation devices are used to stabilize broken bones followed by the healingprocess

Either first generation or second ones

Must be corrosion resistant

Good fatigue properties

Other compatible issues

LECTURE 3 7

Type % C %Cr % Ni %Mn % other elements

301 0.15 16-18 6-8 2.0 1.0Si

304 0.07 17-19 8-11 2.0 1-Si

316, 18-8sMo 0.07 16-18 10-14 2.0 2-3 Mo, 1.0 Si

316L 0.03 16-18 10-14 2.0 2.3 Mo, 0.75Si

430F 0.08 16-18 1.0-1.5 1.5 1.0 Si, 0-6 Mo

CONSTITUENTS OF STEEL

less chromium content should be utilized (because Cr is a highly reactive metal)

Make use of austenite type steel (less magnetic properties)

Lowered carbon content

Inclusion of molybdenum helps corrosion resistance

Electroplating technique (increases corrosion resistance)

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Other features

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Devices Alloy Type

Jewitt hip nails and plates 316 L

Intramedullary pins 316 L

Mandibular staple bone plates 316L

Heart valves 316

Stapedial Prosthesis 316

Mayfield clips (neurosurgery) 316

Schwartz clips (neurosurgery) 420

Cardiac pacemaker electrodes 304

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COBALT CHROMIUM ALLOYS

Cobalt based alloys are used in one of

three forms Cast; as prepared

Wrought (finestructure with lowcarbon contents ;pure forms)

Forged

Cobalt based alloys are better than stainless steel

devices because of low corrosion resistance

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More details

Cast alloy:• a wax model of the implant is made and

ceramic shell is built around the wax model

• When wax is melted away, the ceramic mold has the shape of the implant

• Molten metal alloy is then poured in to the shell, cooling, the shell is removed to obtain metal implant.

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Wrought alloy:

possess a uniform microstructure with fine

grains.

Wrought Co-Cr –Mo alloy can be further strengthened

by cold work.

Forged Alloy:

produced from a hot forging process.

Forging of Co-Cr –Mo alloy requires sophisticated press and complicated

tooling.

Factors make it more expensive to fabricate a device

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TITANIUM BASED ALLOYS

The advantage of using titanium based alloys as implant materials are

low density

good mechano-chemical properties

The major disadvantages

o relatively high cost

oreactivity.

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More details

• a light metal

• Titanium exists in two allotropic forms,• The low temperature -form has a close-packed hexagonalcrystal structure with a c/a ratio of 1.587 at room temperature

• Above 882.50C -titanium having a body centered cubicstructure which is stable

• Ti-6 Al-4V alloy is generally used in one of three conditions wrought, forged or cast

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POLYMERS

Elastomers; able to withstand large deformations and

return to their original dimensions after releasing the

stretching force.

Plastics; are more rigid materials

Thermoplastic (can be

reused, melted)

Thermosetting (can’t)

Elastomers include, butyl rubber,chlorosulfonated polyethylene,epichlorohydrin,rubber,polyurethane,natural rubber and siliconerubber.

Polymers toxicity

Residual monomers due to incompletepolymerization/catalyst used forpolymerization may cause irritations.

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Polymer Specific Properties Biomedical uses

Polyethylene

Low cost, easy Possibility excellent

electrical insulation properties,

excellent chemical resistance,

toughness and flexibility even at low

temperatures

Tubes for various

catheters, hip

joint, knee joint

prostheses

Polypropylene

Excellent chemical resistance, weak

permeability to water vapors good

transparency and surface reflection.

Yarn for surgery,

sutures

Tetrafluoroethylene

Chemical inertness, exceptional

weathering and heat resistance,

nonadhesive, very low coefficient of

friction

Vascular and

auditory

prostheses,

catheters tubes

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Polyethylene structuresThe first polyethylene [PE,(-CH2-CH2-)n] was made by

reactingethylene gas at high pressure in the presence of a peroxidecatalyst for starting polymerization; yielding low densitypolyethylene (LDPE).

By using a Ziegler-Natta catalyst, high-density polyethylene(HDPE)

can be produced at low pressure; (first titanium-basedcatalysts)

The crystallinity usually is 50-70% for low density PE and 70-80%

for high density PE

ultra high molecular weight polyethylene (UHMWPE) …??????

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ACRYLIC RESINS (organic glass)

The most widely used polyacrylate is poly(methylmethacrylate, PMMA) ; The features of acrylic polymers ;

high toughness/strength,

good biocompatibility properties

brittle in comparison with other polymers

excellent light transparency

high index of refraction.

Causes allergic reactions

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BONE CEMENT MIXING AND INJECTION

PMMA powder + MMA liquidmixed in a ratio of 2:1 in a dough, tocure

Injected in the femur (thigh bone)

The monomer polymerizes andbinds together the preexistingpolymer particles.

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Hydrogels

Interaction with H2O, but not soluble

PHEMA; absorbs 60 % of Water, machinable when dry

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HYDROGELSInteresting features

(1) The soft, rubbery nature coupled with minimalmechanical/frictional irritation to the surroundingtissues.

(2) Low or zero interfacial tension with surroundingbiological fluids and tissues, thereby, minimizing thedriving force for protein adsorption and cell adhesion

(3) Hydrogels allow the permeating and diffusion of lowmolecular weight metabolities,waste products and saltsas do living tissues.

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LECTURE 5 BIOMATERIALS 22

POLYURETHANES

Polyther-urethanes; block copolymers (variable length blocks thataggregate in phase domains)

Good physical and mechanical characteristics

Are hydrophilic in nature

Good biocompatibility (blood compatibility)

Hydrolytic heart assist devices

Non-cytotoxic therapy

Consists of hard and soft segments

BIOMATERIALS 23

POLYAMIDES (Nylons)Obtained through condensation of diamine and diacid derivative.

Excellent fiber forming properties due to inter-chain hydrogen bonding and high degree of crystallinity, which increases the strength in the fiber direction.

Hydrogen bonds play a major role

As a catheter

Hypodermic syringes

Diamino hexane + adipic acid

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Next-Generation biomaterials for

Tissue implantation

Skin implantation

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Primary

– Promote controlled

Prevent infection

– Preserve viability of structures

exposed underlying

Long term

– Durable skin cover

healing

– Sensation to key areas

– Permit mobility of

– optimize later

reconstruction

THERAPY GOALS

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Spine,

Cranialmaxillofacial

Dental

Vascular

BoneCartilage

Types of Implants

Implants may be

• Cemented

• Porous coated

• Mesh of holes on implant surface

• Secured as bone in grows

Types of coated implants

Requirements

Excellent physical properties,

corrosion resistant, fatigue strength

Choice of design

Rate, modes of degradation should follow the intended

ways

Low cost, ofcourse

Sterilizable,

Non-toxic, non-carcinogenic, non-

allergic, Biocompatible

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Three so-called 'generations' of biosensors;

First generation; normal product of the reaction diffuses to

the transducer and causes the electrical response.

Second generation; involve specific 'mediators' between

the reaction and the transducer in order to generate

improved response.

Third generation; reaction itself causes the response and no

product or mediator diffusion is directly involved.

Clinical diagnosis and biomedicine

Farm, garden and veterinary analysis

Process control: fermentation control and analysis food and drink

production and analysis

Microbiology: bacterial and viral analysis

Pharmaceutical and drug analysis

Industrial effluent control

Pollution control and monitoring/Mining, industrial and toxic gases

Military applications

LECTURE 3 31

Brief applications of biosensor(s)

By restoring, maintaining,enhancing the tissue, and finallyfunctionalize the organs

Tissue can be grown inside oroutside

Finally to exploit the living cells inmany ways

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Tissue engineering (also referred to as “regenerative medicine)

To create products that improve tissuefunction or heal tissue defects.

Replace diseased or damaged tissue

Because……

Donor tissues and organs are in shortsupply

We want to minimize immune systemresponse by using our own cells ornovel ways to protect transplant

Regenerate

Identify the cues that allow forregeneration without scarring

Like growing a new limb

Repair

Stimulate the tissue at a cell ormolecular level, even at level ofDNA, to repair itself.

Replace

A biological substitute is createdin the lab that can be implantedto replace the tissue or organ ofinterest

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Tissue engineering

The cells themselves

Non-soluble factors within the extracellularmatrix (ECM) such as laminins,collagens,andother molecules

Soluble factors such as cytokines, hormones,nutrients, vitamins, and minerals

cell isolation

cell culture

scaffold material choice

cell scaffold co-culture studies

implantation in animals

human trials

Normal strategies

SkinBoneCartilageIntestine

SUCCESSFULLY ENGINEERED TO SOME EXTENT

Advances in Biomaterials Technology

Cell matrices for 3-D growth and tissue reconstruction

Biosensors, Biomimetic , and smart devices

Controlled Drug Delivery/ Targeted delivery

• New biomaterials - bioactive, biodegradable, inorganic

• New processing techniques

Biohybrid organs and Cell immunoisolation

Value Location pH 6.8 Intracellular 7.0 Interstitial 7.15-7.35 Blood pO2 2-40 Interstitial (mm Hg) 40 Venous 100 Arterial Temperature 37 Normal Core 28 Normal Skin Mechanical Stress 4x10

7 N m

-2 Muscle (peak stress)

4x108 N m

-2 Tendon (peak stress)

Stress Cycles (per year) 3x105 Peristalsis

5x106 - 4x10

7 Heart muscle contraction

Test Conditions:

• where used: skin/blood/brain/mucosal/etc.

Length of implant: Day: Month: Longer:

To more closely replicate complex tissue architectureand arrangement in vitro

To better understand extracellular and intracellularmodulators of cell function

To develop novel materials and processing techniquesthat are compatible with biological interfaces

To find better strategies for immune acceptance

Challenges

Skin Implantation

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Biosensors (invitro/invivo);

analytical devices which convertbiological response into a useful electricalsignal

to determine the concentration ofsubstances either directly or indirectly

areas of biochemistry, bioreactorscience, physical chemistry,electrochemistry, electronics and softwareengineering, and others

http://www.lsbu.ac.uk/biology/enztech/

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Principle of biosensors (bio-recognition systems)

LECTURE 6 BIOMATERIALS 41

biocatalyst (a) converts the substrate to product.

This reaction is determined by the transducer (b)

which converts it to an electrical signal.

The output from the transducer is amplified (c),

processed (d) and displayed (e).

WORKING PRINCIPLE OF BIOSENSOR

distribution of charges

light-induced changes

mass difference

output

Special materials

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Autograft

A graft, or portion of living tissue, taken from one part of thebody and placed in another site on the same individual.

Grafts between two or more individuals allogenic (genetically differentalthough belonging to or obtained from the same species) at one or more loci.

Allograft

Grafts from one species of tissues to other species; Bone marrow engineering

Xenograft

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THREE CLASSES OF CERAMICS (according to their reactivity)

completely resorbable

• More reactive (Calcium phosphate) – over a span of times

• Yielding mineralized bone growing from the implant surface

surface reactive

• Bioglass ceramics ; Intermediate behavior

• Soft tissues/cell membranes

nearly inert

• Less reactive (alumina/carbons) even after thousands of hours

• how minimal interfacial bonds with living tissues.

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Pyrolitic carbon;

• Pyrolysis of hyrdocarbon gas (methane) ≤ 15000 degrees

• Low temperature isotropic (LTI) phase

• Good bonding strength to metals (10 Mpa – 35 Mpa)

• Inclusion of Si with C, wear resistance increases drastically

Vitreous carbon (glassy carbon);

• controlled pyrolysis of a polymer such as phenol formaldehyde

resin, rayon and polyacrylonitrile

• Low temperature isotropic phase

• Good biocompatibility, but strength and wear resistance are not good as LTI carbons

Turbostratic carbon (Ultra low temperature isotropic carbons (ULTI))

• Carbon atoms are evaporated from heated carbon source and

condensed into a cool substrate of ceramic, metal or polymer.

• Good biocompatibility

DIFFERENT VARIETIES OF CARBON (NEARLY INERT CERAMICS)

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Alumina (Aluminium oxide)

•high corrosion resistance•wear resistance• Surface finishing•small grain size•biomechanically correct design•exact implantation technique

Alumina ceramic femoral

component

Natural single crystal alumina known as sapphire

High-density alumina ; prepared from purified alumina powder by isostatic pressing and subsequent firing at 1500-17000C.

-alumina has a hcp crystal structure (a=0.4758 nm and c=1.2999nm)

load bearing hip prostheses and dental implants, hip and knee joints, tibial plate, femur shaft, shoulders, vertebra, and ankle joint prostheses

Porous network ; SEM images

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Glass Ceramics

To achieve a controlled surface reactivity that willinduce a direct chemical bond between the implant and thesurrounding tissues.

Bioglass and Ceravital; fine-grained structure withexcellent mechanical and thermal properties

The composition of Ceravital is similar to bioglass in Sio2

content but differ in CaO,MgO,Na2O.

Bioglass implants have several advantages like

• high mechanical properties

• surface biocompatible properties.

Bioglass

Ceravital

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GLASS CERAMICS

Bioglass and Ceravital are two glass ceramics, fine-grained structure with excellent

mechanical/thermal properties, which are used in implants.

Bioglass (composed of SiO2, Na2O, CaO and P2O5)

Ceravital’s composition is similar to bioglass in Sio2 content but differ in CaO,MgO,Na2O.

highly reactive to aqueous medium and bioactive

Drawbacks: - brittleness, low fracture-resistance due to

mechanical weakness

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Resorbable Ceramics (first resorbable implant material-Plaster of Paris).

• Should not have variable resorption rates

• Should not have poor mechanical properties.

Two types of orthophosphoric acid salt namely -tricalcium phosphate (TCP)and hydroxyapatite (HAP) (classified on the basis of Ca/P ratio).

The apatite- [Ca10 (PO4)6 (OH)2] crystallizes into the hexagonal rhombicsystem. The unit cell has dimensions of a = 0.9432 mm and c = 0.6881 nm.

The ideal Ca/P ratio of hydroxyapatite is 10/6 and the calculated density is3.219 g/ml.

The substitution of OH- with F- gives a greater structural stability due to thefact that F- has a closer coordination than the hydroxyl, to the nearest calcium.

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Questions?