Basics of-

Biomaterial, Bio-implant
and Bio- device.
Interaction with human
tissue.
Important facts And.
Conclusion.
 Prepared By-
Dr. Md Nazrul Islam.
MBBS, M.sc.(BME).
Supervised By-
Associate Prof. Ziaul Haq -
MBBS, MS (Orthopedic).

2
 SECTIONS
-

Biomaterial, Bio-implant and Bio-device.

Biomaterial and Biological Components
Interaction.
Important facts and direction for use.
Conclusion And Our Consensus.
Biomaterial,
Bio-implant / Bio-medical
device:
Overview-

3
Biomaterial,
Bio-implant / Bio-medical
device:
Biomaterial

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:

Bio-Implant

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.
Biomaterial,
Bio-implant / Bio-medical
device:
Bio-Medical Device:
Bio-Medical Device:

Bio-Medical Device" is "an instrument,

apparatus, implement, machine, contrivance,
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
Biomaterial,
Bio-implant / Bio-medical
device:
Historical Advancement:
Biomaterials & Biomedical Devices -
Romans,Chinese,and
Romans,Chinese,and Aztecs Aztecs used
used gold
gold in
in
dentistry
dentistry over
over 2000
2000 years
years ago.
ago.
1860's: 1860's: Lister
Lister develops
develops aseptic
aseptic surgical
surgical technique.
technique.
Early Early 1900's:
1900's: Bone
Bone plates
plates used
used toto fix
fix fractures.
fractures.
1930's:1930's: Introduction
Introduction of of stainless
stainless steel,
steel, cobalt
cobalt
chromium
chromium alloys.
alloys.
1938 1938 :: First
First total
total hip
hip prosthesis
prosthesis (P.
(P. Wiles).
Wiles).
1940's:
1940's: Polymers
Polymers in in medicine:
medicine: PMMA
PMMA bone bone repair;
repair;
cellulose
cellulose for
for dialysis;
dialysis; nylon
nylon sutures.
sutures.
1952:
1952: Mechanical
Mechanical heart heart valve.
valve.
1953:
1953: Dacron
Dacron (polymer
(polymer fiber)
fiber) vascular
vascular grafts.
grafts.
1958:
1958: Cemented
Cemented (PMMA)(PMMA) joint
joint replacement
replacement ..
1960:
1960: First
First commercial
commercial heartheart valves.
valves.
1970's:
1970's: PEO
PEO (poly-ethylene-oxide)
(poly-ethylene-oxide) protein
protein resistant
resistant
thin
thin film
film coating.
coating.
1976: FDA amendment governing testing &
Biomaterial,
Bio-implant / Bio-medical
Statistics:
device:

Biomaterials Biomedical Devices-

8
Biomaterial,
Bio-implant / Bio-medical
Statistics:
device:

Biomaterials Biomedical Devices-

Biomaterial,
Biomaterial:
Bio-implant / Bio-medical
device:
Classification

Biomaterial:
Biomaterial:
Non- Biologica
biological l
Biomateri Biomateria
als: l:
95% of
05% of
total Bio- total Bio-
Natural
Natural
Implant- Implant-
Biologic
Biologic
Hybrid
Hybrid
Biomaterial
Biomaterial
Biomaterial,
Bio-implant / Bio-medical
device:
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.
 Biomaterial,
Bio-implant / Bio-medical
device:
Metals
Metals

Orthopedics'
Orthopedics'
screws/fixation
screws/fixation
Dental
MetalsImplants
Dental Implants // filler
are used as biomaterials
filler due to
their excellent electrical and thermal
conductivity and mechanical properties.
The first metal alloy developed
specifically for human use was the
37.4 Ti vanadium steel .
Alloys

Steels -
Stainles
s
37.3
CoCr Alloys
Biomaterial,
Bio-implant / Bio-medical
device: Polymeric Biomaterials
Drug
Drug Delivery
Delivery Devices.
Devices.
Ear/
Ear/ ocular
ocular implants
implants
Skin
Skin Implant.
Implant.
Cartilage
Cartilage implant.
implant.
Any one
Dental, of a large
Dental, Maxillo-facial
Maxillo-facial and
and varied group
of materials
and ortho-implants,
ortho-implants,
consisting wholly or part of a combination of
carbon and hydrogen (hydrocarbons) It is also a
combination of oxygen, nitrogen and other
oorganic and inorganic
Non-absorbable elements.
Polymer
&
o
Absorbable/Biodegradable
Composition Advantage Disadvantage :
s
Nylon, silicones, Resilient, Not strong, deform
PTFE, UHMWPE easy to with time, may
fabricate degrade
Biomaterial,
Bio-implant / Bio-medical
device:
Ceramic Biomaterials -
Ear/
Ear/ Ocular
Ocular implants
implants
Dental,
Dental, Maxillo-facial
Maxillo-facial and
and ortho-implants,
ortho-implants,
Ceramics are defined as the art
and science of making and using
solid articles that have as their
essential component, inorganic
Non
Biodegradable nonmetallic materials.

Compositio Advantages Disadvanta

n ge :
Highly biocompatible, Brittle,
Aluminum inert, high modulus difficult to
oxide, and compressive make, poor
carbon, strength, good fatigue
hydroxyapa esthetic properties resistance
Natural tite
 Biomaterial,
Bio-implant / Bio-medical
device:
Composite Biomaterials -
Ear/
Ear/ Ocular
Ocular implants
implants
Dental,
Dental, Maxillo-facial
Maxillo-facial and
and ortho-implants.
ortho-implants.

Composites

Fibrous
Composites

Composition Advantages Disadvantage

:
Porous
Porous
Composites
Composites Various Strong, tailor- Difficult to
combinations made make
Particulate
Composites
 Biomaterial,
Bio-implant / Bio-medical
device:
BIOLOGICAL
BIOLOGICAL BIOMATERIAL
BIOMATERIAL
Nature-derived (e.g., plant - derived)
Naturally-derived (e.g., Cell, tissue-)

BIOLOGIC
Stem
Stem cell
cell based/
based/ derived
derived Cell/
Cell/
Tissue.
Tissue.
Stem
Stem cell
cell based/
based/ derived-
derived-
NATURAL
NATURAL Resorbable
Resorbable
Collagen
Collagen Medical
Medical Implant.
Implant.
Stem
Stem cell
cell based/
based/ derived-Tissue
derived-Tissue
Stem Cells Cartilage repair Engine
CORAL Engine
& Preservation of the knee -ering
GELATIN -ering for
for Tissue
Tissue /Organ
/Organ
Regeneration. BASED-
COLLAGEN
Regeneration.
HYBRID/ OR
BIO-IMPLANT
REGENERATION
Semi-synthetic
ORGAN REGROW.
BIOMATERIAL MADE FROM
STEM CELL BASED- COMBINATION
BIO-IMPLANT OF SYNTHETIC AND
REGENERATION BIOLOGIC COMPONENTS.
ORGAN REGROW.

BIOLICAL Cell/ TISSUE REGENERATION.

BIOLOGICAL TISSUE / ORGAN
REPLACEMENT.
Biomaterial,
Bio-implant / Bio-medical
device:
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
Biomaterial,
Bio-implant / Bio-medical
device:
Classification
AndEvolution of Biomaterials-
Synthetic Biomaterials:
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,
4 they are being designed to
stimulate specific cellular responses at the
molecular level in order to help the body to heal
itself.
Biologic Biomaterials:
Bio- replacement-3rd
Generation.
Bio-regeneration- 4th
Generation.
Biomaterial,
Bio-implant / Bio-medical
device:

Cell and Gene-Activating Materials

Genetic Control and Activation.
Molecularly Tailored Resorbable.
Biological Replacement Biomaterial/
Tissue/ Organ.

4th
th Generation

Biomaterial:
Biological Regenerative
Biomaterial.
Biomaterial,
Bio-implant / Bio-medical
device:
Traditional
Biomaterials
Traditional
And Medical Devices
Biomaterials
And Medical Devices
Performance Criteria
Biologically inert
Biocompatible
Non-viableMechanical strength
and funtion
Amenability to engineering
design, manufacturing, and
sterilization
.not found naturally within
the body
Biomaterial,
Next Generation
Bio-implant / Biomaterial
device:
Biomaterials and Medical
Devices-
Revised Performance Criteria
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).
Biological
Components
and Biomaterial
Interaction-

Biomaterial and Human /Biological

Components Interaction Can be
Biomaterial and Protein/
broadly divided / Classified into
Blood.
-
Biomaterial and Cell
Biomaterial and Soft

tissue
Biomaterial and Hard

Tissue/Bone.
 Biological
Components
Biomaterial And
and Biomaterial
Interaction-
Protein, Blood, Cell And Soft
Tissue Interaction:
Injury
Serum / Plasma Protein And Biomaterial
SEQUENCE
SEQUENCE OF
OF HOST
HOST
REACTIONS
REACTIONS Clotting Cascade And Biomaterial.
FOLLOWING
FOLLOWING IMPLANTATION
IMPLANTATION
Host Cell And Biomaterial Interaction.
Provisional matrix formation.
Acute Inflammation (Exaggerated).
Chronic Inflammation (Sp. for foreign-body).
Granulation tissue formation.
ALL STEPS ARE
APPLICABLE
FOR ONLY BIO-INERT
Foreign-body reaction.
-
BIOMATERIAL Fibrosis/Fibrous encapsulation/Non-
FOR BIOACTIVE,
BIORESORPABLE
capsulation .
IMPLANT
Biological
Components
and Biomaterial
Bio-implant
Interaction- And Biological
Interaction:
Immediately After
Implantation-
Infection

Inflammation
Inflammation
Bacterial
Bacterial
Adhesion
Adhesion Leukocyte
Leukocyte
Adhesion
Adhesion and
and
Activation
Activation
Complement
Complement
System
System Activation
Activation

Protein
Adsorption
.. . .....
Biomaterial
Biomaterial

Biological
Biological
Tissue/
Tissue/ Components
Components
Biological
Components
and Biomaterial
Interaction-
Biomaterial
And Tissue Interaction -

Macrophage
s

Fibrosis

The temporal variation in the acute inflammatory

response, chronic inflammatory response, granulation
tissue development, and foreign body reaction to
implanted biomaterials.
Biological
Components
and Biomaterial
Interaction-

1 Second
to
1 Hour:

(Adapted
(Adapted from
from Ratner
Ratner and
and Bryant)
Bryant)
 Biological
Components
and Biomaterial
Interaction-
Biomaterial
Biomaterial
And
And Soft
Soft tissue
tissue Interaction
Interaction --

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 Hydrophilic/Hydrophobic
Gold Same Result
Metal/ceramic/polymer
(long term)
Titanium Hard/soft

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.
 Biological
Components
and Biomaterial
Biomaterial And
Interaction-
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 .

Biological
Components
Biomaterial And
and Biomaterial
Interaction-
Hard Tissue/Bone
Interaction-
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.
 Biological
Components
Biomaterial And
and Biomaterial
Interaction-
Hard Tissue/Bone
Interaction-
Irregular pore structure of porous
Biological Interaction -
coating in Ti5Al4V alloy for bony
ingrowth, from Park and Lakes
[1992].
. Forms mechanical attachment via
bone in growth into pores.
Tissue response is complex, with
several factors affecting it.
Pores must be >100 m diameter
so that capillaries can provide blood
supply to ingrown connective
tissue porous inert implants.
Example-Hydroxy-apatite coated
porous implants.
 Biological
Components
Biomaterial And
and Biomaterial
Interaction-
Hard Tissue/Bone
Interaction- Bioactive Interaction --
Surface-reactive materials;
elicits a
.
specific biological response at
the
surface.
Direct attachment by chemical
Osteoblast cell
attachment on a
bonding 5
composite with bone Implant reacts
Biomaterial
surface-SEM. chemically, at
the surface- Dense, nonporous.
Formation of a hydroxy-carbonate
The mechanism of new bone
formation apatite
an bone bonding to a bioactive (HCA) on surface, when
Biological
Components
Biomaterial
and And
Biomaterial
Interaction-
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. 5

Examples: Calcium sulfate, Tricalcium phosphate

(TCP ).
Challenge: Meeting strength requirements and
short- term mechanical performance while
Bio-degradation
Bio-degradation of
of regeneration of tissues is occuring.
calcium
calcium carbonate
carbonate
particles
particles
Biological
Components
and Biomaterial
Interaction- Protein adsorption
Blood material interactions
Coagulation
Effect
Effectofofthe
theImplant
Implant
on
onthe
theHost-
Host-

Fibrinolysis

Platelet adhesion, activation, release

Complement activation
Leukocyte adhesion, activation
Hemolysis
Toxicity
Modification of normal healing
Encapsulation
Foreign body reaction
Pannus formation
Infection
Tumorgenesis
Biological
Components
and Biomaterial
Interaction-

Embolization
Hypersensitivity
Elevation of implant elements in the blood
Lymphatic particle transport
Effect
of the Host on the Implant -
Physical mechanical effects
Abrasive wear
Fatigue
Stress corrosion, cracking Corrosion
Degeneration and dissolution
Biological effects
Absorption of substances from tissues
Enzymatic degradation
Calcification
Biological
Components
and Biomaterial
Interaction-
Biomaterials
Tissue Interactions Chart-

Local
Interactions Device-
Systemic Associated Complications
(At biomaterialtissue interface) Interactions
Physical-mechanical
Bloodmaterial effects
interactions Wear Thrombosis/
Toxicity Fatigue Embolization
thromboembolism
Modification of Corrosion Hypersensivity Infection
Stress-corrosion cracking
healing Exuberant or
Elevation of
Exaggerated Biological effects defective healing
Inflammation Adsorption of tissue implant elements Biomaterials failure
Prone to Constituents by implant in blood Adverse local tissue reaction
Infection Enzymatic degradation Adverse systemic effect.
Calcification Lymphatic
Particle transport.
Important Facts of
Biomedical
Implants/Devices -
Important Facts of
Biomedical
Selection
Implants/Devices -

criteria for Biomaterials-

Biomaterials and biomedical

devices are used throughout the
human body.
5

2 important aspects must be

Consider before implantation:
Functional performance
Biocompatibility.
 e.g. artificial knee joint).
Control of blood and fluid flow (e.g. artificial heart).
pace filling (e.g. cosmetic surgery).
lectrical stimuli (e.g. pacemaker).
Important Facts of
ight transmission (e.g. implanted lenses).
ound transmission (e.g. cochlear implant).

Biomedical
Implants/Devices -
Selection
criteria for Biomaterials-
Functional
Functional performance:
performance:

Load
Load transmission
transmission and and stress
stress distribution
distribution
(e.g.
(e.g. bone
bone replacement).
replacement).
Articulation
Articulation to to allow
allow movement
movement
(e.g.
(e.g. artificial
artificial knee
knee joint).
joint).
Control
Control ofof blood
blood and
and fluid
fluid flow
flow
(e.g.
(e.g. artificial
artificial heart).
heart).
Space
Space filling
filling (e.g.
(e.g. cosmetic
cosmetic surgery).
surgery).
Electrical
Electrical stimuli
stimuli (e.g.
(e.g. pacemaker).
pacemaker).
Light
Light transmission
transmission (e.g.(e.g. implanted
implanted
lenses).
lenses).
Sound
Sound transmission
transmission (e.g.(e.g. cochlear
cochlear
implant).
implant).
Important Facts of
Biomedical
Implants/Devices -
Selection
criteria for Biomaterials-
Biocompatibility-
Biocompatibility
Arises from differences between
living and non-living materials.
Bio-implants trigger inflammation
or foreign body response.

Biological Compatibility
Chemical Compatibility
Mechanical Compatibility
Nontoxic,
Non-carcinogenic.
Important Facts of
Biomedical
Biomaterials:
Implants/Devices -

Biocompatibility status-

E E E E
L E M M
M E L L
E L E E
M M M M
DEPENDS ON COMPOSITION OF
MATERIAL
Important Facts of
Biomedical
Implants/Devices
Host
Host /Implant -
/Implant Factors:
Factors:
Which
Which Determines
Determines bio-compatibility-
bio-compatibility-

Age and health status

Immunological status
Host Factors: Metabolic status
proper implantation
Tissue damage
Contamination and
Choice of surgeon
Bulk Properties:
Implant Factors: Surface Properties:
Mechanical Properties:
Long-term Structural Integrity:
Important Facts of
Biomedical
Success
Implants/Devices -

of an Implant is Determined by-

Conditions of Patient.
Surgeon Technical Skills.
Biocompatibility of Implant.
Mechanical Properties.
Corrosion Resistance.
Important Facts of
Biomedical
Precautions
Implants/Devices -

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.
Important Facts of
Biomedical
Implants/Devices -

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
Evolving definitions:
definitions:
 Conclusion
And Our
Consensus:

Our Consensus : 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,
Painless administration of a
Physical,
vaccine by tiny Electrical,
microneedles on a skin patch.
Toxicological,
 Conclusion
And Our
Consensus:

Our Consensus :
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,
VeriChip Human
Implantable Microchip
Proper implantation and
post implantation patient
 We
We Are
Are
Grateful
Grateful To
To ::

Professor
Professor Shamimul
Shamimul Haq
Haq
Associate
Associate Prof. Dr. Ziaul
Prof. Dr. Ziaul Haq
Haq
Associate
Associate Prof. Dr Paritosh Chandra
Prof. Dr Paritosh Chandra Debenath
Debenath
Associate
Associate Prof. Dr. Sheikh Abbas Uddin Ahmed
Prof. Dr. Sheikh Abbas Uddin Ahmed
Associate Prof. Dr. Md Golam Kabir
Associate Prof. Dr. Md Golam Kabir Miah Miah
Associate
Associate Prof.
Prof. Dr.
Dr. Monoarul
Monoarul Islam
Islam
Associate
Associate Surgeon Dr. Aminur Rahman
Surgeon Dr. Aminur Rahman
Assistant
Assistant Prof.
Prof. Kazi Shamim uzzaman
Kazi Shamim uzzaman
Assistant
Assistant Prof.
Prof. S.M. Quamrul Akther
S.M. Quamrul Akther Sanju
Sanju
Assistant
Assistant Prof. Bahar Uddin
Prof. Bahar Uddin
Dr. Ibnul
Dr. Ibnul Hasan
Hasan ofof Department
Department ofof Orthoped
Orthoped
And Mr Sanouar Hossain &
And Mr Sanouar Hossain & Kazi Kazi Afsar
Afsar Udd
Udd
THE ACME Laboratories, Dhaka,
THE ACME Laboratories, Dhaka, Bangla Bangla
&

Sponsored By:
THE ACME- Laboratories
Ltd,
6