basics of- human biomaterials, implantable medical devices and biomedical science:

Biomaterial, Bio-implant

and Bio- device.

Interaction with human tissue.

Important facts And.

Conclusion.

2

Prepared By-

Dr. Md Nazrul Islam.MBBS, M.sc.(BME).

Supervised By-

Associate Prof. ZiaulHaq -MBBS, MS (Orthopedic).

3

Biomaterial, Bio-implant / Bio-medical device:

A biomaterial is any material (other

than drug), natural or synthetic, that

is used to make bio-implant, bio-

medical device that

treats, augments, or replaces any

tissue, organ and/or any body

function.

Biomaterial, Bio-implant / Bio-medical device

Any substance other than the drug made of

Biomaterial-s that can be used for

any period of time as part of a system that

treats augments or replaces any tissues,

organ, or functions of the body,

And-

It is usually intended to remain there for a

significant period of time.

Bio-Implant


Bio-Medical Device:

“Bio-Medical Device" is "an

instrument, apparatus, implement, machine, contr

ivance, implant,in-vitro reagent, or related article

including any component, part or

accessory, which is:

Intended for use in the diagnosis of disease/other conditions, or in the cure, mitigation, treatment, or prevention of disease. Intended to affect the structure /function of

human system -And does not achieve any of it's primary

intended purposes through chemical action within or on

And is not dependent upon being metabolized in the Body.


Historical Advancement:Biomaterials & Biomedical Devices -

Romans,Chinese,and Aztecs used gold in

dentistry over 2000 years ago.

1860's: Lister develops aseptic surgical technique.

Early 1900's: Bone plates used to fix fractures.

1930's: Introduction of stainless steel, cobalt

chromium alloys.

1938 : First total hip prosthesis (P. Wiles).

1940's: Polymers in medicine: PMMA bone repair;

cellulose for dialysis; nylon sutures.

1952: Mechanical heart valve.

1953: Dacron (polymer fiber) vascular grafts.

1958: Cemented (PMMA) joint replacement .

1960: First commercial heart valves.

1970's: PEO (poly-ethylene-oxide) protein resistant

thin film coating.

1976: FDA amendment governing testing &

production of biomaterials /devices.

1976: Artificial heart W. Kolff, Prof.Emeritus U of U).


8

Statistics:Biomaterials Biomedical Devices-


Statistics:Biomaterials Biomedical Devices-


Biomaterial: Classification

Non-

biological

Biomaterial

s:

Biological Biomaterial:

Natural

Biologic

Hybrid

Biomaterial

95% of total Bio-Implant-

05% of total Bio-Implant-


Non-Biological(Synthetic) Biomaterial -

.

Non-biological-

Synthetic materials, are made of

polymer/ Metal/Ceramic or

Composite, suitable for implanting in a

living body to -

Repair

Replace

Augment

or

Regenerate

damaged or diseased parts.


Metals

Metals are used as biomaterials due to their excellent electrical and thermal conductivity

and mechanical properties. The first metal alloy developed specifically

for human use was the “vanadium steel” .

•Orthopedics' screws/fixation• Dental Implants / filler

Steels -

Stainless

37.3

CoCr Alloys

37.4 Ti

Alloys


Polymeric Biomaterials

Composition Advantages Disadvantage :

Nylon, silicones,

PTFE, UHMWPE

Resilient,

easy to

fabricate

Not strong, deform with

time, may degrade

Any one of a large and varied group of materials

consisting wholly or part of a combination of

carbon and hydrogen (hydrocarbons) It is also a

combination of oxygen, nitrogen and other

organic and inorganic elements.

o Non-absorbable Polymer &

o Absorbable/Biodegradable


Ceramic Biomaterials -

Ceramics are defined as the art and

science of making and using solid

articles that have as their essential

component, inorganic nonmetallic

materials. Non

Biodegradable

Natural

Composition Advantages Disadvantage

:

Aluminum

oxide,

carbon,

hydroxyapati

te

Highly biocompatible,

inert, high modulus and

compressive strength,

good esthetic properties

Brittle,

difficult to

make, poor

fatigue

resistance


Composite Biomaterials -

Composites

Particulate

Composites

Porous

Composites

Fibrous

Composites

Composition Advantages Disadvantage :

Various

combinations

Strong, tailor-

made

Difficult to make


BIOLICAL Cell/ TISSUE REGENERATION.

BIOLOGICAL TISSUE / ORGAN

REPLACEMENT.

Stem cell based/ derived Cell/ Tissue.

Stem cell based/ derived- Resorbable

Collagen Medical Implant.

Stem cell based/ derived-Tissue Engine

-ering for Tissue /Organ Regeneration.

BIOLOGICAL

BIOMATERIAL

NATURAL

CORAL

GELATIN

BIOLOGIC

HYBRID/ OR

Semi-synthetic

COLLAGEN BASED-

BIO-IMPLANT

REGENERATION

ORGAN REGROW.

STEM CELL BASED-

BIO-IMPLANT

REGENERATION

ORGAN REGROW.

BIOMATERIAL MADE FROM

COMBINATION

OF SYNTHETIC AND

BIOLOGIC COMPONENTS.


Biological/Natural vs. synthetic materials -

• Biological/Natural pros/cons

– built-in bioactivity

– poor mechanical strength

– immunogenicity (xenologous sources)

– lot-to-lot variation, unpredictable.

• Synthetic pros/cons

– biocompatibility may be difficult to predict,

must be tested.

– mechanical and chemical properties readily

altered.

– minimal lot-to-lot variation

• Synthetic advantages: tunable and reproducible.


4

Biologic Biomaterials:Bio- replacement-3rd

Generation. Bio-regeneration- 4th

Generation.

• First Generation Biomaterials: materials used in applications that are requested to be inert in the human body environment. • Second Generation Biomaterials: designed to be

Bioactive Resorbable.

• Third Generation Biomaterials: by combining these two properties, they are being designed to stimulate specific cellular responses at the molecular level in order to help the body to heal itself.

Synthetic Biomaterials:

ClassificationAnd–Evolution of Biomaterials-


Cell and Gene-Activating Materials

Genetic Control and Activation.

Molecularly Tailored Resorbable.

Biological Replacement Biomaterial/

Tissue/ Organ.

Biological Regenerative

Biomaterial.

4th Generation

Biomaterial:


Traditional BiomaterialsAnd Medical Devices

Biologically inert

Biocompatible

Non-viableMechanical strength and

funtion

Amenability to engineering

design, manufacturing, and sterilization

….not found naturally within the body

Performance Criteria


Next Generation Biomaterials and Medical Devices-

Biologically inert

Non-viable

Biocompatible

Mechanical strength and function

Amenability to engineering design, manufacturing, and sterilization

Biodegradable

Induces cell and tissue integration

“Smart” (i.e., physiologically-responsive)

“Instructional” (i.e., controls cell fate).

Revised Performance Criteria

Biomaterial, Bio-implant / Biomaterial device

Biomaterial and Protein/ Blood.

Biomaterial and Cell

Biomaterial and Soft tissue

Biomaterial and Hard Tissue/Bone.

Biomaterial and Human /Biological

Components Interaction Can be broadly

divided / Classified into -–

Biomaterial And Protein, Blood, Cell And Soft Tissue Interaction:

ALL STEPS ARE

APPLICABLE

FOR ONLY BIO-INERT

BIOMATERIAL-

FOR

BIOACTIVE, BIORES

ORPABLE IMPLANT

Inflammation

Complement

System

Activation

Leukocyte

Adhesion and

Activation

Bacterial

Adhesion

Infection

Biomaterial

Protein

Adsorption

Biological

Tissue/ Components

. . . . . . . .

Bio-implant And Biological Interaction:Immediately After Implantation-

BiomaterialAnd Tissue Interaction -

Macrophages

Fibrosis

The temporal variation in the acute inflammatory

response, chronic inflammatory

response, granulation tissue development, and

foreign body reaction to implanted biomaterials.

(Adapted from Ratner and Bryant)

1 Second

to

1 Hour:

Materials:Short-Term Reaction:Long-Term Reaction:

Polyethylene 1. Different protein 1. Fibrous

Hydroxyapatitie adsorption Encapsulation

Polyurethane 2. Varied activation of

Silicone host response

pHEMA

PTFE

Pyrolytic carbon

Gold

Titanium

Hydrophilic/Hydrophobic

Metal/ceramic/polymer

Hard/soft

Same Result

(long term)

Sequence of events involved in inflammatory and wound healing responses

leading to foreign body giant cell formation.

This shows the importance of Th2 lymphocytes in thetransient chronic

inflammatory phase with the production of IL-4 and IL-13, which can

inducemonocyte/macrophage fusion to form foreign body giant cells.

BiomaterialAnd Soft tissue Interaction -

Biomaterial And Hard Tissue/Bone Interaction

Biomaterial and Hard tissue/ Bone

Interaction Can be Classified into -

Morphological Interaction

Biological Interaction

Bioactive Interaction

Biodegradable/ Bioresorption

or Scaffold Interaction.

This implant for a total hip replacement is

designed with various porous surfaces that

encourage tissue in growth.

Interactions Between Implant and Body in Fracture .

.

Morphological Interaction -

Implant is inert or nearly inert

Device: dense, nonporous, nearly

inert.

Mechanism: mechanical interlocking

Does not form bond with tissue

(bone).

Tissue response is dependent on fit

rather than chemistry.

Example: single crystal and poly-

crystalline Al2O3.

Biomaterial And Hard Tissue/Bone Interaction-


.

Biological Interaction -

Forms mechanical attachment via bone “in growth” into pores.

Tissue response is complex, with several factors affecting it.

Pores must be >100 µm diameter so that capillaries can provide blood supply to ingrown connective tissue porous inert implants.

Example-Hydroxy-apatite coated porous implants.

Irregular pore structure of porous

coating in Ti5Al4V alloy for bony

ingrowth, from Park and Lakes

[1992].

5

.

Bioactive Interaction --

Surface-reactive materials; elicits a

specific biological response at the

surface.

Direct attachment by chemical bonding

with bone Implant reacts chemically, at

the surface- Dense, nonporous.

Formation of a hydroxy-carbonate apatite

(HCA) on surface, when implanted

Example-Bioactive glasses, bioactive glass-

ceramics (Ceravital), hydroxyapatite

(Duraptite.Calcitek); bioactive composites

Palavital)..

The mechanism of new bone formationan bone bonding to a bioactive ceramic.


Osteoblast cell attachment on a composite Biomaterial surface-SEM.

5

Biomaterial And Hard Tissue/ Bone Interaction

.

Biodegradable/

Bioresorption or Scaffold Interaction -

Resorption rates must match “repair” rates of

body tissue.

Constituents of resorbable implant must be

metabolically acceptable.

Designed to degrade with time, and replaced

with natural tissues.

Reactions will persist until components have been

removed.

Examples: Calcium sulfate, Tricalcium phosphate

(TCP ).

Challenge: Meeting strength requirements and

short- term mechanical performance while

regeneration of tissues is occuring.

Protein adsorption

Blood material interactions

Coagulation

Fibrinolysis

Platelet adhesion, activation, release

Complement activation

Leukocyte adhesion, activation

Hemolysis

Toxicity

Modification of normal healing

Encapsulation

Foreign body reaction

Pannus formation

Infection

Tumorgenesis

Embolization Hypersensitivity Elevation of implant elements in the blood Lymphatic particle transport

Physical – mechanical effects• Abrasive wear• Fatigue• Stress corrosion, cracking Corrosion• Degeneration and dissolutionBiological effects• Absorption of substances from tissues• Enzymatic degradation• Calcification

Effect of the Host on the Implant -

Local

Interactions

(At biomaterial–tissue interface)Systemic

Interactions

Device-

Associated Complications

• Blood–material

interactions

• Toxicity

• Modification of

healing

• Exaggerated

Inflammation

• Prone to

Infection

Physical-mechanical

effects

• Wear

• Fatigue

• Corrosion

• Stress-corrosion cracking

Biological effects

• Adsorption of tissue

Constituents by implant

• Enzymatic degradation

• Calcification

•Embolization

•Hypersensivity

• Elevation of

implant elements

in blood

•

Lymphatic t

ransport.

• Thrombosis/

thromboembolism

• Infection

• Exuberant or

defective healing

• Biomaterials failure

• Adverse local tissue reaction

• Adverse systemic effect.

Biomaterials–Tissue Interactions Chart-

5

Selection criteria for Biomaterials-

Biomaterials and biomedical

devices are used throughout the

human body.

2 important aspects must be

Consider before implantation:

– Functional performance

– Biocompatibility.

Important Facts of Biomedical Implants/Devices -

Functional performance:

– Load transmission and stress distribution

(e.g. bone replacement).

– Articulation to allow movement

(e.g. artificial knee joint).

– Control of blood and fluid flow

(e.g. artificial heart).

– Space filling (e.g. cosmetic surgery).

– Electrical stimuli (e.g. pacemaker).

– Light transmission (e.g. implanted lenses).

– Sound transmission (e.g. cochlear implant).

Selection criteria for Biomaterials-


(e.g. artificial knee joint).– Control of blood and fluid flow (e.g. artificial heart).– Space filling (e.g. cosmetic surgery).– Electrical stimuli (e.g. pacemaker).– Light transmission (e.g. implanted lenses).– Sound transmission (e.g. cochlear implant).

Biocompatibility-

• Arises from differences between living and non-living materials.

• Bio-implants trigger inflammationor foreign body response.

Important Facts of Biomedical Implants/Devices -Selection criteria for Biomaterials-

Biological Compatibility

Chemical Compatibility

Mechanical Compatibility

Nontoxic,

Non-carcinogenic.

Biomaterials: Biocompatibility status-

E E E E

E

E

E

E E E

M

M M

M M M M

L

L L

L

DEPENDS ON COMPOSITION OF MATERIAL


Host /Implant Factors:Which Determines bio-compatibility-

Bulk Properties:

Surface Properties:

Mechanical Properties:

Long-term Structural Integrity:

Age and health status

Immunological status

Metabolic status

proper implantation

Tissue damage

Contamination and

Choice of surgeon

Host Factors:

Implant Factors:


Success of an Implant is Determined by-

Conditions of Patient.

Surgeon Technical Skills.

Biocompatibility of Implant.

Mechanical Properties.

Corrosion Resistance.


Precautions To Be Taken For The Patients of-

Documented Renal diseases.

Cardiovascular diseases

precluding elective surgery.

Metabolic bone diseases.

Radiation bone therapy.

Patient on steroid medication.

Long-term infection / Chronic

infection.

Pregnancy and nursing.


Contraindications

• Severe vascular or neurological disease •Uncontrolled diabetes.• Severe degenerative disease.• Severely impaired renal function.• Hyper-calcemia, abnormal calcium metabolism • Existing acute or chronic infections, especially

at the site of the operation.• Inflammatory bone disease such as osteomyelitis• Malignant tumors.

Patients who cannot or will not follow post-

operative instruction, including individuals

who abuse drugs and/or alcohol .


Evolving definitions:

Biomaterials/ Bio-devices are of very

important instrument of medical science.

End-use application must be a

consideration.

Compatibility in one application may not be

compatible for another.

Material and device characteristics and

properties to consider –

Chemical,

Physical,

Electrical,

Toxicological,

Morphological and

Mechanical Conditions of tissue

exposure

(Nature, degree, frequency and

Painless administration of a

vaccine by tiny

microneedles on a skin patch.

VeriChip Human

Implantable Microchip

Merely, we give attention to asses

Biocompatibility,

Functional performance and

patient compliance:

Those points should be assed before

Implantation.

We should have to be more/very careful

about –

Absolute indication,

Choice of biomaterial,

Biocompatibility,

Functional performance,

Proper implantation and

post implantation patient

compliance.

basics of- human biomaterials, implantable medical devices and biomedical science:

Health & Medicine