BIO MATERIALS & ITS APPLICATIONS

Ashish Kumar GoudaB.Tech, Metallurgical Engg., NIT, Rourkela, India

Materials aspect- metals, polymers and ceramics and their suitability as biomaterials

Plan of Discussion

Cells, Types of tissues and their structure-function, wound healing

Materials and methods used for implant and transplant

Soft and Hard Tissue and Their Replacement

Ethical Issues

Metals Polymers Ceramics Composites

Introduction to Biomaterials and General Overview

• Biomaterials or Biomedical materials are used to repair,

replace or augment diseased, damaged or worn out parts of

the body• We plan to discuss --------• The present material science update - replacement of tissue

– overview of the clinical need for replacement or

augmentation of tissues and organs• Examples of the wide range of device and approaches used

to repair or replace diseased or damaged part of tissue or

organs• Limitations of spare body parts• New approaches to tissue and organ repair

Introduction

Spare Body Parts - Is it desirable? Is it Possible or Fiction?

Integration of biomechanical and bioelectrical devices with a living body – a science fiction concept a couple of decades back – now a reality in surgery (artificial heart valves, pacemakers)

So what is a distant imagination today may be a reality after some time!

So our knowledge base has a limited vision and the vision keeps on changing with time and new ideas

Science Fiction Stories for more than 100 years have forecasted many of the present day technical developments

Implants Transplants Science Fiction

Cloning Tissue Engineering

CYBORG (1970)– a novel by Martin Caiden describes about Steve Austin- An Air Force Test Pilot who had an implanted bionic arm, a bionic eye

The novel describes the use of neuro muscular stimulation for bionic arm control and the use of implanted bionic eye for vision restoration

Science - Fiction

- Reality

Origin of concept of Shelter

Source: Prof S K Guha IIT KGP

Fundamental concept of Mechanical Engineering

Clamping/Fixing

Originated from Grip of Hand

Social

Self

Nature

The 3 Worlds of Knowledge

The belief that science creates certainty is a fallacy….

The uncertainty in biological system is high due to the presence of large number of inorganic and organic (biological) molecules and their mutual interaction within themselves as well as with the environment

Increased life expectancy of patients gives rise to a very large need in healthcare for the aged.

• Osteoporosis • Parkinson’s/ Alzheimer’s • Heart Disease/ Stroke • Arthritis • Diabetes

A new name is added to the transplant list every 18 minutes

Number of replacement parts fitted in the US per year

• Mammary prostheses 400 000• Pacemakers 200 000• Heart valves 40 000• Intraocular lenses 1 000 000• Orthopaedic implants 1 000 000(Hips, knees, shoulders, fingers etc)• Orthopaedic fixation 1 000 000(Plates, pins, screws)• Spinal Surgery 400 000

The decrease in bone density can be as high as 40 -50% - increases fracture probability

The reason for the decrease in bone density is due to slow repair rate of bones

Repair of bones require a series of sequential cellular events

A disruption in any of these sequential events of cellular change required to repair the damaged bone lead to the formation of scar tissue at the interface with the implants

Connective Tissues

Cells which make things Cells which eat (resorb) things

Cells & Extracellular Matrix

MacrophagesOsteoclastsChrondoclasts

FibroplastsOsteoblastsChrondoblastsLipoblasts

Cells which provide skeletal strength

Osteocytes

In addition to decreased density of trabecular bone above, ageing also gives rise to a decrease in the thickness of cortical bone

30-year-old normal bone 60-year-old osteoporotic bone

A diagram of the shearing of the femoral head from bone, which is a direct consequence of a torsional load applied to a decreased trabecular bone structure.

A Progressive deterioration in the quality of connective tissues with ageBone loss is severe among aged women (50+)

Increase in the population where the number of 50+ is rapidly increasing

Increasing confidence among surgeons and patients that implants will improve quality of life of the patients

Availability of highly reliable prostheses as well the Infrastructure for better post-operative care and recovery

Increased Demand for Implants/Transplants - Reasons

The Past –Removal of TissueWhen options were limited the damaged or diseased tissues were removed by amputation

An Orthotic deviceRepair or Replacement of damaged tissue

The available alternatives for the replacement of damaged or diseased tissues

• An Implant (Prostheses) – An object inserted or embedded surgically • in the body

• A Transplant – a tissue or organ removed from one part of the body to another

- coronary bypasses using patients own veins, Spinal fusion -patient’s bone

Autograft - one part of a person to another location in the same person

Homograft (One human to another human) – Genetic differences▼

rejection by immune system

Xenograft (another species to human) – technical and ethical limitation- used

only for non-living tissue replacement (porcine heart valve,

demineralized bovine bones as a bone graft

A prosthesis is a man made device used inside the body to replace or augment damaged or diseased part of the body

Between transplant and implant- implants are the first choice

Limited availability of transplants and the associated ethical issues- Implants are easily the first choice

Goal of replacement of parts of the body is to re-establish equilibrium.

A young person has a balance between the biomechanical behaviour of all parts of the body and the biochemical nature of the cells and tissues that comprise the living structure. With age this equilibrium of balance between biomechanics and biochemistry often deteriorates

The objective of use of implants in the body is an attempt to restore this equilibrium

• No manmade, artificial, material available today can completely match the biomechanical characteristics of living tissues.

• No manmade material is capable of repairing itself. • No manmade material or device is capable of adjusting its structure and

properties to changes in the environment or mechanical loads that it is encountering.

Transplants v Implants – A compromise

• Consequently all materials and all devices, prostheses in use today are a compromise.

Problems of Transplant

Demand is more than availability- 5 to 7 times more than the supply

The problem is acute for kidney and heart

Solutions can be through sales (legal?), donors (siblings, family, natural death and accident victims) – removal and preservation also requires prompt action

No national or international policy on donation and distribution

Immunological problem – patient starts to leave on drugs - High cost

Animal transplant – Ethical?

Ethical issue

Intraocular Lens

Light is focused through a bio-inert polymer lens (PMMA) which is fixed with a polymer connector. Bone cement is used for cold curing

Dr. De Bakey holding up a new version of an artificial heart based on a continuous pump modified from the high velocity pumps developed at N.A.S.A. The continuous stream of blood pumped by this small pump appears to offer a better solution for preserving blood circulation than the pulsatile pumps that have been tried, generally unsuccessfully, for more than thirty years. Dr. De Bakey, who is now 90+ years of age, has worked his entire life to achieve a solution to the replacement of a diseased heart and it is still only in very limited trials.

An Artificial Heart?

This Fig. from a Sunday Times’ article (1998) suggests that laboratory grown hearts will be available within ten years to solve the donor crisis. The example used is the tissue engineering success of growing a simulated ear on the back of a mouse. The difference between a collagen construct and skin in the shape of an ear to a functioning organ such as a heart is immense. It is generally believed that tissue engineering offers hope in this direction and is an important part of this teaching module. However it is unlikely that the current rate of progress of tissue engineering will yield a functioning heart within ten years, in contrast to claims presented in the popular press.

A Tissue Engineered Alternative?

Artificial HeartsThe first artificial heart was patented by Paul Winchell in 1963

Jarvik 7Akutsu-III

Abiocor IIAbiocor CardioWest ™

JarvikLiotta

chambered heart of Cockroach

Staged Multi-actuated Pump System

Diaphragms (of increasing

stiffness from 1 to 5)

Geared motor

Electromagnetic adjustable

armInlet

Outlet

1

54

3

2

The field of orthopedic surgery has been revolutionized as a result of the use of implants. Fracture fixation, such as repair of a sheared femoral head, by the use of fracture fixation plates and nails is now commonplace and has restored mobility to hundreds of thousands of patients. This figure illustrates the use of this type of internal fixation device.

Orthopaedic Repair By Fixation

The cup is made of Ultra High MolecularWeight polyethylene

The head is a articulating ball

Cement is still attached to theAcetabular component

•Morphological Fixation-Mechanical anchoring

•Biological Fixation-Ingrowth of tissue into pores of implant

•Bioactive Fixation-Chemical bonding of tissue to implant

Alternative to bone cement

In order to understand the use of biomaterials in the form of implants or prostheses, it is necessary to appreciate that there are several alternative paths of tissue reaction to implanted materials.

Tissue responses to materials

TYPES OF MATERIALS: tissue responsesTOXIC: Death of the surrounding tissueNON-TOXIC/RESORBABLE: Replacement by the surrounding TissueNON-TOXIC, INACTIVE: Formation of a non-adherent thin fibrous capsuleNON-TOXIC, BIOACTIVE: Formation of an interfacial bond with surrounding tissues

ExamplesTOXIC:Metals that release ions such as nickel, chromium or cobalt. Degrading polymers releasing unpolymerzied monomers.

NON-TOXIC:RESORBABLE: Certain polymers (polyglycolic acid) used as sutures (stitches), which are gradually replaced over several weeks by tissue.

INACTIVE: Stainless steels, titanium alloys, ceramic, polyethylene, used in long term implants.

BIOACTIVE: Materials that can bond to tissue, such as certain compositions of glasses and ceramics.

Vocal cords.

The Bioreactivity Spectrum

What is the need for testing for biocompatibility?

• Biomaterials and medical devices constitute an extremely diverse, heterogeneous category of items.

• Macro-micro-nano devices/materials• Biodegradable/Non-biodegradable• To ensure Bio-safety

Regulatory Guidelines For Biocompatibility Safety Testing(International Organization for Standardization (ISO) 10993-1/EN 30993-1)

• Under continuous revision & modification.

• More research is needed at cellular, subcellular &

molecular level for defining the regulatory guideline.

• Difficulty in projecting long term safety in human

situation based on results of in-vivo animal studies.

TESTS WHICH ARE REQUIRED……..

1. Haemocompatibility2. Tests for cytotoxicity (In-vitro).3. Test for local effect after implantation.4. Skin sensitization, dermal irritation and intracutaneous

reactivity 5. Systemic toxicity (acute, chronic)6. Immunotoxicity7. Genotoxicity8. Carcino/mutagenicity9. Reproductive toxicity10. Toxicity study for degradation products & leachables.

Why is it difficult to project long term safety of implants/devices/delivery systems?

• Lack of tools for studying cellular dysfunction or cellular stress.

• Kinetics or mechanism of cellular adaptation or differentiation ?

• Gene – environment interaction ?

Metals

Acti-nide

seriesRaFr

RnAtPoBiPbTlHgAuPtIrOsReWTaHfRare earth series

BaCs

XeITeSbSnInCdAgPdRhRuTcMoNbZrYSrRb

KrBrSeAsGeGaZnCuNiCoFeMnCrVTiScCaK

ArClSPSiAlMgNa

NeFONCBBeLi

HeH

LwNoMdFmEsCfBkCmAmPuNpUPaThAc

LuYbTmErHoDyTbGdEuSmPmNdPrCeLa

The Periodic Table

The periodic table showing the metals (yellow), non-metals (red) and intermediate (blue) elements. Metals are good conductors of heat and electricity, opaque to visible light, and have a familiar metallic lustre.

Metallic materials are inorganic substances-usually combination of

metallic elements- Iron, titanium, aluminium, gold

May also contain small amounts of non metallic elements – carbon,

nitrogen, oxygen

Rarely used as a pure element but usually mixed other elements to form an alloy- Necessary to obtain the required combination of properties iron alloyed with Cr –steel, zinc with Cu -brass

Metals are used for orthopaedic applications- high strength of metals, in internal electrical devices, in orthodontics and artificial implantsImportant biomaterials- SS, Co-alloys, Ti alloysNitinol – has shape memory effect is also important, Ag, Pt, Au – inert and noble effect

Three factors affect the choice of metals and alloys as biomaterials

- Physical and mechanical properties

- Degradation of the material

- Biocompatibility

Properties Processing route

Microstructure

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One model of a metal, positive ions are surrounded by a sea or cloud of electrons. These ‘free electrons’ are not bound to any particular metal ion but are free to move around within the structure. It is these ‘free electrons’ that result in some of the typical properties of a metal including the good conductance of heat and electricity, and the metallic lustre of a polished surface.

Electron Cloud Model

A A

A AA A

AAA

AA

AA

AB B B B

B B B

C CC

C C C C

B B B B

B B B

C

C

C C

C CC

A A

A AA A

AAA

AA

AA

A

The face centred cubic (f.c.c.) structure can be considered as a repeating stack of closely packed layers of hard spheres – Al, Ni, Fe (at high temperature) have this type of crystal structure

Alternatively, many of the mechanical properties of metal can be better understood by considering the atoms as hard spheres

Considering two closely packed layers, each containing 6

spheres arranged in a triangle, pointing down in the first

layer and up in the other. One sphere is placed in the recess

of the spheres below the lower layer and another sphere in

the recess above the upper layer. The two structures re

stacked so the atoms sit in a ABCA sequence.

A A

A AA A

AAA

AA

AA

AB B B B

B B BC CC

C C C C

B B B B

B B B

A A

A AA A

AAA

AA

AA

A

The hexagonal close packed structure also consists of a stack of closely stacked planes, however this time the stacking sequence is ABABAB…. Like the f.c.c. structure each sphere is touching 12 others.Zinc, magnesium and titanium (at room temperature) all have this type of structure.

Solid Sphere Model – h c p

a

z

h.c.p.

A hexagonal prism can be seen in this structure by taking atoms from three of the closely packed planes, ABA.

< B >

< B >

< B > < B >

The bcc structure does not contain closely packed planes. The structure can be contained in a cube with a sphere centred on each corner and a sphere in the centre of the cube. Each sphere is only touching 8 other spheres.Chromium, Iron (at room temperature) and Ti (at high temperature) all have this type of structure.

Solid Sphere Model – b c c

5m10m

Metallic Fracture

Image is of a metal which has fractured along the grain boundaries in a brittle manner.

Typical fracture surface of a metal that has failed in a more ductile manner.

200

250

300

350

400

450

500

0 5 10 15 20 25

d-1/2

Yeild

Stre

ss M

Pa

Graph showing the effect of grain size on the yield stress of a commercially pure titanium alloy.

Effect of grain size

Hall – Petch Relation YS=0+K d-1/2

0

Plastic DeformationNon-reversible

Fracture

Tensile Strength

Yield Stress

Recoverable Elastic Strain

Typical stress strain behaviour of a metallic material tested in tension. The metal behaves elastically for the blue portion of the curve, permanent (plastic) deformation (red section) begins at the yield stress of the metal, a maximum stress is reached, the stress then decreases until ultimately the metal fractures.

Tensile properties of metals

Young’s Modulus

(GPa)

Yield Stress(MPa)

Tensile Strength (MPa)

% elongation

Fracture Toughness (MPam1/2)

Steels (General)

210 210-1600 400-1800 10-40 50-90

Stainless Steels

190-210 200-1650 400-1800 5-40 80

Titanium Alloys

100-115 170-1100 400-1200 10-30 40-70

Platinum 170 10 120-240 1-40 -

High and sudden stresses can be encountered in the body in orthopaedic applications and the metal must withstand theses stresses without permanent deformation or fracture

Mechanical properties of metals

The implant material should also have modulus close to the natural bone- best possible joining and the least damage to the parts of the bone where it is attached avoidance of stress shielding effect

Ben

ding

Stre

ss, S

, MP

a

Number of Cycles to Failure, N105 106 107 108 109

100

400

300

200

0

Mild Steel

Aluminium

Fatigue Limit

Fatigue properties of metals

The typical way of presenting fatigue data is a graph of the alternating stress against the log of number of cycles to failure. The two types of fatigue behaviour are shown here, the first in green is the behaviour of many non-ferrous alloys such as aluminium. The number of cycles to failure increases as the alternating stress decreases. The second type of behaviour, in red is typical of ferrous alloys and titanium alloys, a fatigue limit is observed. Below this stress the metal has an effectively infinite fatigue life.

Heat

Cool

Correspondence Variant A

Correspondence Variant B

Correspondence Variant A

DeformHeat

Correspondence Variant A

Correspondence Variant B

Correspondence Variant A

The shape memory effect

Can happen with both T and Load

As the metal is heated and cooled the atomic arrangement changes between one of high symmetry at high temperature to a lower symmetry arrangement at low temperature. Several variants of the lower symmetry phase will form. The arrangement will change backwards and forwards as the metal is heated and cooled with no overall shape being observed. If the metal is deformed whilst it is in its low temperature structure the atoms move in such a way that one variant grows at the expense of the others. If the metal is then heated to return to the higher symmetry structure the metal will return to is original shape. This is the shape memory effect.

Oulu University - http://herkules.oulu.fi/isbn9514252217/html/x317.html

Spinal vertebrae (A) and shape memory spacers (B) in the martensitic state (left) and in the original shape (right).

Dentists are using devices made from SMA for different

purposes. NiTi based SMA material performs exceptionally at

high strains in strain-controlled environments, such as

exemplified with dental drills for root canal procedures. The

advantage of these drills is that they can be bent to rather large

strains and still accommodate the high cyclic rotations.

Superelastic SMA wires have found wide use as orthodontic

wires as well. Lately a special fixator for mounting bridgework

has been developed.