Introduction to Biomaterials

What is a Biomaterial?
• A material intented to interface with biological systems
to evaluate, treat, augment or replace any tissue, organ
or function of the body.

• It is a non viable material used in a medical device,

intended to interact with biological system.

• A biomaterial is defined as any systemically,

pharmacologically inert substance or combination of
substances utilized for implantation within or
incorporation with a living system to supplement or
replace functions of living tissues or organs.
 Biomaterials- Introduction
• The ability to replace or augment damaged organs, or
blood vessels or tissues in part or as a whole has
improved the scope of human life.

• In addition, a variety of extracorporeal devices, such as

the heart, lung and blood dialysis machines are used
commonly in medical technology.

• The availability of human organs is difficult which has

paved the way for the use of synthetic materials .
 Functions of Biomaterials
• The functions of implants fall in to one of the categories:

• Load bearing or transmission

• The control of fluid flow in order to stimulate normal

physiological function or situation

• Passive space filling either for cosmetic reasons or functional

reasons or functional reasons or functional reasons

• Generation of electric stimuli and transmission of light and

sound.
• The only alternate to artificial implants is transplantation of
organs such as heart, kidney etc., but this effort has been
hindered due to social, ethical and immunological problems.
• Biocompatibility is the ability of material to perform within
an appropriate host response in a specific application.

• Biocompatibility in other words is the quality of not having

toxic or injurious effects on biological systems.
• Each biomaterial has a particular lifespan in the human
body.

• Examples of specific applications include a hemodialysis

membrane, a urinary catheter or hip-joint prosthesis.

• Hemodialysis membrane might be in contact with the

patient’s blood for 3 hours.

• The catheter may be inserted for a week after which it

starts infecting.
 Biomaterials For Applications
• Skeletal system
• Joint replacements -Titanium, stainless steel, polyethylene

• Plate for fracture fixation - Stainless steel, cobalt-

chromium
• alloy

• Bone cement - Poly(methyl methacrylate)

• Artificial tendon and ligament-Teflon, Dacron

• Dental Implants-Titanium, alumina,calcium phosphate

 • Cardiovascular system

• Blood vessel prosthesis - Teflon, Dacron,

Polyurethane

• Heart valve -Reprocessed tissue, Stainless steel,

carbon

• Catheter - Silicone rubber, Teflon, polyurethane

 • Organs

• Artificial Heart - Polyurethane

• Artificial Kidney - Cellulose,polyacrylonitrile

• Heart Lung Machine - Silicone rubber

 • Senses

• Cochlear replacement -Platinum electrodes

• Intraocular lens - Poly(methyl methacrylate)

,hydro gel

• Contact Lens - Silicone-acrylate,hydrogel

• Corneal bandage – Collagen,hydrogel

Typical Biomaterial Application
Typical Biomaterial Application
Glass Ceramic Cochlear Implants
Subjects Integral to Biomaterials
• Toxicology

• Healing

• Mechanical and Performance requirements

 Healing
• Special processes are invoked when a material or
device heals in the body.

• Injury to tissue will stimulate the well-defined

inflammatory reaction sequence that leads to healing.

• Where a foreign body (e.g., an implant) is present in

the wound site (surgical incision), the reaction sequence
is referred to as the "foreign body reaction.

• Furthermore, this reaction will differ in intensity and

duration depending upon the anatomical site involved.
 Toxicology
• A biomaterial should not be toxic, unless it is specifically
engineered for such requirements.

• Since the nontoxic requirement is the norm, toxicology

for biomaterials has evolved into a sophisticated science.

• It deals with the substances that migrate out of

biomaterials.

• It is reasonable to say that a biomaterial should not give

off anything from its mass unless it is specifically
designed to do so.
 Mechanical and Performance
Requirements
• Biomaterials that have a mechanical operation must perform
to certain standards and be able to cope with pressures.

• It is therefore essential that all biomaterials are well designed

and are tested.

• Biomaterials that are used with a mechanical application, such

as hip implants, are usually designed using CAD (Computer
Aided Design)
 Historical Development of
Biomaterials
• Some of the earliest biomaterial applications were as far
back as ancient Phoenicia where loose teeth were bound
together with gold wires for tying artificial ones to
neighboring teeth.

• In the early 1900’s bone plates were successfully

implemented to stabilize bone fractures and to accelerate
their healing.

• While by the time of the 1950’s to 60’s, blood vessel

replacement were in clinical trials and artificial heart
valves and hip joints were in development.
 Historical Development of
Biomaterials

• 600 B.C Samhita Nose construction

• 1893-1912 W.A.Lane Steel screws for fixation

• 1912 W.D.Sherman Use of Vanadium steel plate

• 1938 P.Wiles First total hip replacement

 Historical Development of
Biomaterials
• 1952 A.B.Voorhees Blood Vessel

• 1953 A.Kantrowitz Intraortic balloon pumping

• 1960 M.I.Edwards Heart valve

• 1980 W.J.Kolff Artificial Heart

 Heart Valve Prosthesis
• Heart valves open and close over 40 million times a year and
they can accumulate damage sufficient to require replacement
in many individuals.

• More than 80,000 replacement valves are implanted each

year in the United States .

• There are many types of heart valve prostheses and they are
fabricated from carbons, metals, elastomers, plastics, fabrics
and animal or human tissues
• Generally, almost as soon as the valve is implanted, cardiac
function is restored to near normal levels and the patient shows
rapid improvement.

• In spite of the overall success seen with replacement heart

valves, there are problems that may differ with different types
of valves; they include induction of blood clots, degeneration
of tissue, mechanical failure, and infection.
 Artificial Hip Joints

• After 50 or more years of cyclic mechanical stress, or

because of degenerative or rheumatological disease, the
natural joint wears out, leading to considerable loss of
mobility and often confinement to a wheel chair.

• Hip-joint prostheses are fabricated from titanium,

stainless steel, special high-strength alloys, ceramics,
composites, and ultra high-molecular-weight
polyethylene.
 Artificial Hip Joints

• With some types of replacement hip joints and surgical

procedures that use polymeric cement, ambulatory
function is restored within days after surgery.

• For other types, a healing period is required for

integration between bone and the implant before the
joint can bear the full weight of the body.

• After 10-15 years, the implant may loosen,

necessitating another operation.
 Dental Implants
• The widespread introduction of titanium implants has
revolutionized dental implantology.

• These devices form an implanted artificial tooth anchor upon

which a crown is affixed.

• One of the primary advantages originally cited for the

titanium implant was its osseous integration with the bone of
the jaw.

• Loss of tissue support leading to loosening along with

infection remains an issue in the topic of Dental implants.
 Intraocular Lenses
• A variety of intraocular lenses (IOLs) have been
fabricated of poly methyl methacrylate, Silicone
elastomer, soft acrylic polymers, or hydro gels and are
used to replace a natural lens when it becomes cloudy
due to cataract formation.

• Good vision is generally restored almost immediately

after the lens is inserted and the success rate with this
device is high.

• s IOL surgical procedures are well developed and

implantation is often performed on an outpatient basis.
 Steps Involved in the Development
The various steps involved in the development of biomaterial
devices are

• Identifying a need

• Device design

• Material Synthesis

• Material Testing
 Steps Involved in the Development
• Fabrication

• Sterilization and Packaging

• Device Testing

• Clinical Use
Examples
 Biomaterials
• Polymeric biomaterials

• Bioceramics

• Metallic biomaterials

• Biocomposite

• Biologically based (derived) biomaterials

Some application of biomaterials
• Skeletel system
• Joint replacement(Hip, knee)
• Bone plate
• Bone cement
• Artificial tendon and ligment
• Dental implant

• Cardiovascalar sysem
• Blood vessel prosthesis
• Heart valve
• Catheter
• Organs
• Artificial heart
• Skin repair template
• Artificial kidney
• Heart-lung machine

• Senses
• Cochlear replacement
• Intraocular lens
• Contact lens
• Corneal bandage
 Types of Materials
• Titanium , Stainless steel, PE
• Stainless steel, Co-Cr alloy
• PMMA
• Hydroxylapatie Teflon, Dacron
• Titanium, alumina, calcium phosphate
• Dacron, Teflon, Polyurethane
• Reprocessed tissue, Stainless steel, Carbon
• Silicone rubber, teflon, polyurethane
• Polyurethane
• Silicone-collage composite
• Cellulose, polyacrylonitrile
• Silicone rubber
• Platium electrodes
• PMMA, Silicone rubber, hydrogel
• Silicone-acrylate. Hydrogel
 Biocompatibility
• Biocompatibility: The ability of a material to perform with an
appropriate host response in a specific application.

• Host response: the reaction of a living system to the presence

of a material.

• B=f(X1,X2......Xn)

• Where X: material, design, application etc.

 Medical Device
• It does not achieve its principal intended action in or on the
human body by pharmacological, immunological or metabolic
means, but it may be assisted in its function by such means.
 Polymerization
• Condensation: A reaction occurs between two molecules to
form a larger molecule with the elimination of a smaller
molecule.

• Addition: A reaction occurs between two molecules to form a

larger molecule without the elimination of a smaller molecule.
Polymeric Biomaterials: Advantages

• Easy to make complicated items

• Tailorable physical & mechanical properties

• Surface modification

• Immobilize cell etc.

• Biodegradable
 Polymeric Biomaterials:
Disadvantages
• Leachable compounds

• Absorb water & proteins etc.

• Surface contamination

• Wear & breakdown

• Biodegradation

• Difficult to sterilize
 Polymeric Biomaterials
• PMMA
• PVC
• PLA/PGA
• PE
• PP
• PA
• PTFE
• PET
• PUR
• Silicones
 Bioceramic: Advantages
• High compression strength

• Wear & corrosion resistance

• Can be highly polished

• Bioactive/inert
 Bioceramic: disadvantages

• High modulus (mismatched with bone)

• Low strength in tension

• Low fracture toughness

• Difficult to fabricate
 Bioceramics
• Alumina

• Zirconia (partially stabilized)

• Silicate glass

• Calcium phosphate (apatite)

• Calcium carbonate
 Metallic Biomaterials:Advantages

• High strength
• Fatigue resistance
• Wear resistance
• Easy fabrication
• Easy to sterilize
• Shape memory
Metallic Biomaterials:Disadvantages

• High moduls

• Corrosion

• Metal ion sensitivity and toxicity

• Metallic looking
 Metallic biomaterials
• Stainless steel (316L)

• Co-Cr alloys

• Ti6Al4V

• Au-Ag-Cu-Pd alloys

• Amalgam (AgSnCuZnHg)

• Ni-Ti

• Titanium
Surface modification (treatment)
• Physical and mechanical treatment

• Chemical treatment

• Biological treatment
 Deterioration of Biomaterials
• Corrossion

• Degradation

• Calcification

• Mechanical loading

• Combined
 General Criteria for materials
selection
• Mechanical and chemicals properties

• No undersirable biological effects

carcinogenic, toxic, allergenic or immunogenic

• Possible to process, fabricate and sterilize with a godd

reproducibility
 Material Properties
• Compresssive strength
• Tensile strength
• Bending strength
• E-Modulus
• Coefficient of thermal expansion
• Coefficient of thermal coductivity
• Surface tension
• Hardness and density
• Hydrophobic/philic
• Water sorption/solubility
• Surface friction
• Creep
• Bonding properties
 Cell/tissue reaction to implant

• Soft tissue

• Hard tissue

• Blood cells
 The biological milieu
• Atomic scale

• Molecular scale

• Cellular level

• Tissue

• Organ

• System

• Organism
Sequence of local events following
implantation in soft tissue
• Injury

• Actute inflammation

• Granulation tissue

• Foreign body reaction

• fibrosis
Soft tissue response to an implant
• Actut (mins to hrs)

Cell type: Leukocytes

Function: Recognition, engulfment and degradation (killing)

• Chronic (days to months)

Cell types: Macrophages, monocytes and lymphocytes.

• Granulation tissue formation (3-5 days)

Cell types: Endothelial cells (forming blood vesssels), fibeoflasts (forming connnective
tissue)

• Foreign body reaction (days to life time)

Cell types: Foreign body giant cells, Macrophages, fibroblasts

• Fibrosis & Fibrous encapsulation

Cell type: Fibroblasts

 Bioactive and Osteointegration
• A chemical bonding between bone and material will be
formed. (Bioactive, Hydroxylapatite)

• A direct contact between bone and impant under light

microscope. (Osterintegration, titanium)
 Blood material interaction

• Hemolysis (red cells)

• Coagulation (Platelets)
 Standards

• Test methods

• Materials standards

• Device standards

• Procedure standards
 ISO 10993 and EN 30993
• ISO 10993-1: guidance on selection of tests
• ISO 10993-2: Animal welfare requirements
• ISO 10993-3: Test for genotoxicity, carcinogenicity and reproductive
toxicity
• ISO 10993-4: Selection of tests for interactions with blood
• ISO 10993-5: Tests for cytotoxicity: In vitro methods
• ISO 10993-6: Test for local effects after implantation
• ISO 10993-7: Ethylene oxide sterilization residuals
• ISO 10993-8: Clinical investigation
• ISO 10993-9: Degradation of materials related to biological testing
• ISO 10993-10: Tests for irritation and sensitization
• ISO 10993-11: Tests for systemic toxicity
• ISO 10993-12: Sample preparation and reference materials
 Testing of Biomaterials
• Physical and mechanical

• Biological

In vitro assessment

in vivo assessment

Functional assessment

Clincal assessment
 Biomaterials applications
• Dental implant

• Tooth fillings

• Vascular implants

• Drug delivery, bone fixing pine, suture

• Bone defect fillings

• Hip joint prosthesis bone plate

• Scaffolds for tissue engineering

• Contanct lens
3-principles in dental implant design

• Initial retention

• Anti-rotation mechanics

• No sharp-edges
 Tooth fillings materials

• Amalgam

• Dental composite

• Ceramics

• Other metals
 General criteria for tooth filling
materials
• Non-irritation to pulp and gingival
• Low systemic toxicity
• Cariostatic
• Bonding to tooth substance without marginal leakage
• Not dissolved or erode in saliva
• Mechanical strength, wear resistance, modules matching
• Good aesthetic properties
• Thermal propertiesy (expansion & conductivity)
• Minimal dimensional changes on setting and adequate
working time and radio opacity
 Textile structure and vascular
implant

• Weaving

• Braiding

• knitting
 Tissue engineering
• The application of engineering disciplines to either maintain
existing tissue structures or ti enable tissue growth.

• From a material engineering pint of view, tissues are

considered to be cellular composites representing multiphase
system:
Three main structural components:
1. Cells organised into functional units
2. The extracellular matrix
3. Scaffolding architecture
 Polymer concepts in tissue
engineering
• Fabrication procedures of a porous polymer 3D scaffold:

 PLGA dissolved in chloroform and mixed with NaCl

particles, evaporation of the chloroform, dissoltion of NaCl in
water, resulting a polymer sponge with over 96% porosity.
 Requirements for Soft Tissue
Adhesive
• Biodegradable

• Fast spread on wet (wound) surface

• Adequate working time

• Adequate bonding strength

• Hemostasis

• Biocompatible
 Contact lens
• Optical properties

• Chemical stability

• Oxygen transmissibility

• Tear film wettability

• Resistance to lipid/protein deposition

• Easy to clean