Biomaterials and biosciences biometals.pptx

Introduction to Materials
Evolution of Materials
Stone Age
Bronze Age
Iron Age
Concrete Age
Silicon Age
Now?
Materials drive our society

Materials science: Studies the relationships that exist
between the structures and properties of materials.
Materials engineering: Designing or engineering a material
with a predetermined set of properties on the basis of the
structure property correlations.
Why should we know about materials? Because it is the job
of the engineer to select materials for given application
based of materials structure, properties, processing,
performance and cost.
Materials selection based on optimization, property
degradation, cost etc.
What is Materials science and engineering?

Screw Driver- a simple
device

The effectiveness and behaviour of each material will depend on
three factors
1. Structure
2. Properties 3. Processing
Performance

Same material – aluminium oxide – different processing
method – different structure
Single crystal
Polycrystalline
made of very small
single crystals
Polycrystalline
with pores
Adapted from Fig. 1.2,
Callister & Rethwisch 8e.
(Specimen preparation,
P.A. Lessing; photo by S.
Tanner.)

With out material there is no engineering
Materials are classified into two categories
Crystalline Amorphous
Another Way of Classification
advanced materials— biomaterials, smart
materials, and nanoengineered materials

Classification of Materials
Metals:
Composed of one or more metallic elements (such as iron,
aluminium, copper, titanium, gold, and nickel), and often also non-
metallic elements (for example, carbon, nitrogen, and oxygen) in
relatively small amounts.
Atoms in metals and their alloys
are arranged in a
very orderly manner.
Fig. 1.08 Callister & Rethwisch
8e.
Properties:
Stiff and strong, but ductile
High thermal & electrical conductivity
Opaque, reflective
High density

 They are most frequently oxides, nitrides, and carbides.
Examples: aluminum oxide (or alumina, Al2O3), silicon dioxide (or
silica, SiO2), silicon carbide (SiC),
silicon nitride (Si3N4), clay minerals
(i.e., porcelain), cement, and glass.
Fig. 1.09 Callister & Rethwisch 8e.
Properties:
Brittle, glassy, Strong
Non-conducting (insulators)
Optical characteristics – can
be transparent, translucent,
or opaque
Ceramics can be defined as solid compounds that are formed by the
application of heat, and sometimes heat and pressure, comprising at
least two elements provided one of them is a non-metal or a
nonmetallic elemental solid. The other element(s) may be a metal(s)
or another nonmetallic elemental solid(s).

Composites:
A composite consist of two (or more) individual materials formed
from metals, ceramics, and/or polymers.
The design goal of a composite is to achieve a combination of
properties that is not displayed by any single material, and also to
incorporate the best characteristics of each of the component
materials.
Example: fibreglass
Made of small glass fibres
embedded within a polymeric
material (epoxy).
Properties:
stiff, strong (from the glass)
flexible, and ductile (from polymer)

Polymers (plastics or rubber):
Many polymers are organic compounds that are chemically based on
carbon, hydrogen, and other non-metallic elements (O, N, and Si).
Inorganic polymers also exist such as silicon rubber.
Very large molecular structures
often chain-like in nature.
Fig. 1.10 Callister & Rethwisch
8e.
Properties:
Soft, ductile, low strength, low density
Thermal & electrical insulators
Optically translucent or transparent

Crystal Structure
1. Calculate the volume of an FCC unit cell in terms of the atomic radius R
2. Calculate the atomic packing factor for the FCC crystal structure
3. Copper has an atomic radius of 0.128 nm, an FCC crystal structure, and an
atomic weight of 63.5 g/mol. Compute its theoretical density
Three relatively simple crystal structures are found for most of the common metals:
Face centered cubic Body-centered cubic Hexagonal close-packed
CN:12
Equivalent atoms: 4
CN:8
Equivalent atoms: 2
CN:12
Equivalent atoms: 6

Concept of Grain and Grain Boundaries

Stress Strain Response of Materials
 Concept of Engineering Stress and Engineering Strain
 How the True Strain concept is essential
 How the True Stress concept is required?
 Description of strength parameters
 How to quantify ductility?
 Concept of Toughness

Stress Strain
Tension Compression Shear
Three types of static stress that materials experience:
Tends to stretch Tends to squeeze Adjacent portion slide
against each other

Mechanical Properties in Designing and Manufacturing
Mechanical properties determine a material’s behaviour
when subjected to mechanical stresses
Properties include elastic modulus, ductility, hardness, and
various measurement of strength
Improved mechanical properties is not always beneficial !
High strength usually make manufacturing more difficult

Stress Strain
Engineering Stress
Engineering Stress

Strength and Stiffness
Stiffness
Stiffness is the rigidness of any object or material. Objects with a high stiffness will resist
changes in shape when being acted on by a physical force. Stiffness depends on the
modulus of elasticity, also known as Young’s Modulus. While strength can vary from
grade to grade, Young’s Modulus is constant for any given metal and is independent
of external stressors such as heat treatment, processing, or cold work.
In simple terms, when it comes to strength vs. stiffness, the strength of metal can
change throughout the object, but its stiffness will remain constant.
Example: a rubber band is an example of a material with low stiffness. On the other
hand, diamond is a material with high stiffness.
Strength
Strength is a measure of the stress that can
be applied to a material before it
permanently deforms (yield strength) or
breaks (tensile strength). If the applied
stress is less than the yield strength, the
material returns to its original shape when
the stress is removed. If the applied stress
exceeds the yield strength, plastic or
permanent deformation occurs, and the
material can no longer return to its original
shape once the load is removed.

Strength and Stiffness
Ductility: The ability of a material to be deformed plastically without fracture
Elongation up to the point of necking- is a measure of necking
Toughness: Total area under the stress-strain graph
Resilience: Area the stress-strain graph in elastic part
True stress ? – Based on instantaneous area
True strain ?
Strength coefficient
Strength hardening
exponent

Metal as Biomaterials
Point defect-Vacancies and self-interstitials
1. Edge dislocation
A dislocation is a linear or one-dimensional
defect around which some of the atoms are
misaligned. an extra portion of a plane of
atoms, or half-plane, the edge of which
terminates within the crystal. This is termed an
edge dislocation; it is a linear defect that
centers around the line that is defined along
the end of the extra half-plane of atoms.
The equilibrium number of vacancies Nv for
a given quantity of material depends on and
increases with temperature according to
N is the total number of atomic sites,
Qv is the energy required for the
formation of a vacancy,
T is the absolute temperature in kelvins,
k is the gas or Boltzmann’s constant.
Line defect-Dislocation

Line defect-Dislocation 2. Screw dislocation
screw dislocation, may be thought of as being formed by a shear stress that is
applied to produce the distortion

Interfacial defects
Grain Boundary
External surfaces, grain boundaries, twin boundaries,
stacking faults, and phase boundaries.

1. Strengthening by grain size reduction
Strengthening mechanism in metals
The size of the grains, or average grain
diameter, in a polycrystalline metal
influences the mechanical properties.
Adjacent grains normally have
different crystallographic orientations
and, of course, a common grain
boundary. During plastic deformation,
slip or dislocation motion must take
place across this common boundary—
say, from grain A to grain B
The grain boundary acts as a barrier to dislocation motion for two reasons:
1. Since the two grains are of different orientations, a dislocation passing into grain B will
have to change its direction of motion; this becomes more difficult as the
crystallographic misorientation increases.
2. The atomic disorder within a grain boundary region will result in a discontinuity of slip
planes from one grain into the other.
Hall-Petch equation

2. Solid solution strengthening
Another technique to strengthen and harden metals is alloying with impurity atoms that go
into either substitutional or interstitial solid solution. Accordingly, this is called solid-
solution strengthening. High-purity metals are almost always softer and weaker than alloys
composed of the same base metal. Increasing the concentration of the impurity results in
an attendant increase in tensile and yield strengths
Alloys are stronger than pure metals because impurity atoms that go into solid solution
ordinarily impose lattice strains on the surrounding host atoms. Lattice strain field
interactions between dislocations and these impurity atoms result, and, consequently,
dislocation movement is restricted.

2. Solid solution strengthening

3. Strain hardening
The strain-hardening phenomenon is explained on the basis of dislocation-dislocation
strain field interactions. The dislocation density in a metal increases with deformation or
cold work, due to dislocation multiplication or the formation of new dislocations,
Strain hardening is the phenomenon whereby a ductile metal becomes harder and
stronger as it is plastically deformed.
4. Strengthening from fine precipitates

BioMaterials
What is biomaterial?
Can we consider wood and bone as biomaterials?
What about hearing aids and artificial limbs?
The success of the biomaterial dependent on which factors?
Properties
 Biological
 Mechanical
 Physical
 Chemical
Biomaterials
The field of biomaterials is multidisciplinary, and the design of
biomaterials requires the synergistic interaction of materials science,
biological science, chemical science, medical science and mechanical
science.

BioMaterials
Example: Characteristics that a bone plate must satisfy for stabilizing
a fractured femur after an accident.

BioMaterials
Class of materials used in body

Different Materials in Bio-Implants
Hip Prosthesis
Stent
Bone plate and Screw

Biocompatibility
Broadly, biocompatibility is defined as the ability of a material to perform with
an appropriate host response in a specific application that is, the material and
the tissue environment of the body should coexist without having any
undesirable or inappropriate effect on each other.
From a biological point of view, biocompatibility arises from the acceptability of
non - living materials (synthetic biomaterial) in a living body (mammal/human).
Biomaterials must be
1. Biochemically compatible, non - toxic, non - irritable, non - allergenic and non
- carcinogenic;
2. Biomechanically compatible with surrounding tissues; and
3. A bio adhesive contact must be established between the materials and living
tissues.
Biocompatibility depends on place of applications, why?
For example, a specific material could be biocompatible in bone replacement,
but the same material may not be biocompatible in direct blood contact
application.

Host Response
In order to develop new materials, it is desirable to understand the
in vivo host response of various biomaterials. Ideally, biomaterials
should not induce any change or provoke undesired reaction in the
neighboring or distant tissues. An important aspect of host
response involves the formation of a structural and bio logical bond
between the material and host tissues. When the biocompatibility
is lacking, materials cause tissue reactions, which may be systemic
or local. Systemic responses can be toxic or allergic and triggered
by the products of metallic corrosion and polymer degradation,
release of micro particles from materials, and the presence of
contaminants.

Host Response
Depending on the biocompatibility and host reaction, biomaterials can
be broadly classified into three main categories on the basis of various
types of host responses of bio materials after implantation into the
living body:
a) Bioinert / biotolerant: Bioinert materials are biocompatible
materials, but cannot induce any interfacial biological bond between
implants and bone.
b) Bioactive: Bioactive materials are a group of biocompatible
materials that can attach directly with body tissues and form chemical
and biological bonds during early stages of the post implantation
period.
c) Bioresorbable: Bioresorable materials are the type of
biocompatible materials that are gradually resorbed before they
finally disappear and are totally replaced by new tissues in vivo.

Bone
Bone is a two-phase composite material with organic (flexible) and inorganic
(rigid) components
Bone is composed of three major constituents:
1.Living cells (osteoblasts, osteoclasts, and osteocytes),
2.Non-living organic proteins (collagen, muco-polysaccharides),
3.Non-living inorganic crystals (hydroxy-carbonate apatite, HCA).
Osteoblasts are “bone growing cells”.
Osteoclasts are “bone resorbing cells”.
Osteocytes are mature bone cells

Bone
Bone Cells and Bone Remodelling
Bone is constantly responding to the physiological and biomechanical demands of the
body. Bone atrophies (i.e., resorbs and decreases in mass and mineral content) when it is
not used, and hyper trophies (i.e., increases in magnitude) when it is stressed. This is in
accordance with Wolff’s law, which states that “every change in the form and the function
of a bone or in the function of the bone alone, leads to changes in its internal
architecture and in its external form.” This process is formally referred to as bone
remodeling.
The events of bone remodeling are carried out by two unique kinds of cells, osteoblasts
and osteoclasts. These cells are in constant and direct communication and provide the
correct interaction and environment for bone development. Osteoclasts are specialized
for bone resorption by modulating collagen and the hydroxyapaptite lattice of previously
formed bone. Osteoclasts have this capacity as a consequence of the secretion of
proteases and acid onto the bone surface. In contrast, osteoblasts are the principle cells
responsible for bone formation. They are formed from precursor cells called
osteoprogenitor cells, which are mesenchymal stem cells that are located in the vicinity of
all bony surfaces.

Bone
 Once peak bone mass has been developed, bone remodeling occurs for
approximately 10% of the bone surface.
 These inactive areas are covered by bone-lining cells (considered to be
deactivated osteoblasts), which are conduits for transmitting the status of the
mineralized matrix to the bone remodeling units.
 The information conveyed by the bone-lining cells can signal for an increase in
osteoblast precursors when an increase in bone density is needed, or stimulate
osteoclastogenesis (the process of forming osteoclasts) to induce the resorption
of the bone matrix.
 This process plays a critical role in bone remodeling, especially in weight-bearing
bones. The interplay between the cells changes the rigidity and strength of bone,
which determine bone mass and body weight.
 If bone receives less than the adequate stress needed, a subsequent decrease in
bone density will result. This mechanism is evident in weightless environments
and immobilization. For example, astronauts who are in space for an extended
period of time can experience a noticeable amount of bone loss, similar to that
seen in disabled patients who have been immobile for an extended period of time
(Friedman 2006)

Bone

Bone
SEM micrograph of a femur
The structure of long bones

Bone- Mechanical Properties
Anisotropic behaviour of cortical bone specimens from a human femoral
shaft tested in tension.

Affect of Age on Bone
Graph showing the relationship among bone mass, age, and sex and the
changes in cross-section that occur to a long bone during aging.

Bone Grafting
Bone loss may be associated with musculoskeletal disorders,
infections, degenerative changes, traumatic events etc.
Bone grafting is a surgical procedure that replaces missing bone in
order to repair bone fractures that are extremely complex, pose a
significant health risk to the patient, or fail to heal properly. Some
small or acute fractures can be cured without bone grafting, but the
risk is greater for large fractures like compound fractures.
The ideal bone graft or bone graft substitute should provide the
following three elements:
(1) an osteoconductive matrix to support bone ingrowth,
(2) osteoinductive factors to induce bone healing, and
(3) osteogenic cells to facilitate bone regeneration.
Bone grafts can be autografts, allografts, xenografts

Bone Grafting
Osteoconductive and osteoinductive are two terms that describe
the properties of bone graft materials.
Osteoconductive material acts as a structural framework for bone
growth
Osteoinductive material contains factors that stimulate bone
growth and induction of stem cells into bone-forming cells.
Osteoconduction provides the guidance, while osteoinduction
encourages the transformation of undifferentiated cells to active
bone cells.
When is bone grafting a good option?
Bone grafts are a good option for patients who have damaged or diseased bone
and require extra support to repair it. It is commonly used when patients have
fractures that have not healed well, or to fill defects caused by trauma (injury),
infection, and/or disease. In some cases, the broken bones are in good contact,
but there is a lack of healing. Bone grafting stimulates healing in such situations.

Bone Grafting
Autograft
 Bone graft that is derived from the patient’s own tissue. The bone tissue may be
harvested from the iliac crest, femur, or tibia, and then placed in the defect site.
 Autografts have been considered the “gold standard” for bone grafts. They
provide an osteoconductive, osteogenic scaffold for bone cells as well as
endogenous (i.e., the patient’s own) biological healing factors, such as bone
morphogenetic factors and angiogenic growth factors to promote new bone
formation and blood vessel development, respectively.
 Disadvantage with autografts:
 Need for a separate surgical procedure to procure donor tissue, which increases
surgery time and the likelihood of infection, inflammation, donor-site pain, and
other complications. The incidence of complications has been reported to be as
high as 50%.
 There is only a finite amount of tissue available for autografting needs. In spite of
these limitations, autografts are still considered as the gold standard and used in
the majority of modern bone-grafting procedures done. Other grafting alternatives
are adopted in case there is not enough endogenous bone available or that the
accessible tissue cannot be grafted because of underlying pathological disorders.

Bone Grafting
Allograft
 Allografts are similar to autografts, but the main difference is that the tissue is
coming from a cadaver as opposed to the patient. This is usually obtained through
a bone bank, similar to a blood bank. Like any organ, bone can be donated after
death, and kept in a bank for future use.
 Like autografts, allografts are osteoconductive, and depending on the processing
methods used, they can even retain osteoinductive factors (i.e., bone-healing
factors) such as bone morphogenetic protein (BMP).
 Disadvantage: 1. Although allografts are unlimited in supply, concerns with
disease transmission and foreign body response limit their clinical use. Allograft
processing methods such as freeze drying have been somewhat effective in
curbing viral and bacterial transfer to the graft-receiving patients. Freeze drying
decreases the amount of foreign particles, and hence, effectively reduces the
foreign body response. 2. Unlike an autograft, the allograft does not contain live
cells, and purely acts as a structural scaffold for the patient’s bone to grow into.
The patient’s bone will eventually replace the donor bone as more growth occurs.
 By subjecting the bone to mild acids, allografts can be demineralized, and such
matrices can be easily converted into various shapes and forms (i.e., powders,
putties, and gels) to be used in clinic as graft material for filling bone defects.

Bone Grafting
Xenograft
 any procedure that involves the transplantation, implantation, or infusion into a
human recipient of either (a) live cells, tissues, or organs from a nonhuman animal
source or (b) human body fluids, cells, tissues or organs that have had ex vivo
contact with live non-human animal cells, tissues, or organs”
 Advantage: almost infinite amount of nonhuman animal tissue that might be
considered for transplantation
 Disadvantage is the risk of cross-species disease transmission
Synthetic graft
 To overcome the drawbacks associated with autografts, allografts, and xenografts,
many biomaterials have been synthesized. Artificial bone can be created from
ceramics such as calcium phosphates (e.g., hydroxyapatite and tricalcium
phosphate), bioglass, and calcium sulfate, all of which are biologically active to
different degrees depending on solubility in the physiological environment

Blood Compatibility
The single most important requirement for blood-interfacing
implants is blood compatibility. Although blood coagulation is the
most important factor for blood compatibility, the implants should
not damage the proteins, enzymes, and formed elements of blood.
The latter includes hemolysis (red blood cell rupture) and initiation
of the platelet release reaction.
Factors Affecting Blood Compatibility
The surface roughness is an important factor since the rougher the
surface the more area is exposed to blood. Therefore, a rough
surface promotes faster blood coagulation than the highly polished
surfaces of glass, polymethylmethacrylate, polyethylene, and
stainless steel.
Surface wettability — i.e., hydrophilic (wettable) or hydrophobic
(non-wettable) — was thought of as an important factor.

Blood Compatibility
Surface charge: The surface of the intima of blood vessels is negatively
charged (1–5 mV) with respect to the adventitia. This phenomenon is
associated partially with the nonthrombogenic or throm-boresistant
character of the intima since the formed elements of blood are also
negatively charged and hence are repelled from the surface of the intima.
This was demonstrated experimentally in canine experiments by using a
copper tube that is a thrombogenic material implanted as an arterial
replacement. When the tube was negatively charged, clot formation was
delayed to a few days when compared with the control, which clotted
within a few minutes.
The chemical nature of a material surface interfacing with blood is closely
related to the electrical nature of the surface since the type of functional
groups of polymer determines the type and magnitude of the surface
charge. No intrinsic surface charge exists for metals and ceramics, although
some ceramics and polymers can be made piezoelectric. The surface of
intima is negatively charged largely due to the presence of polysaccharides,
especially chondroitin sulfate and heparin sulfate.

Blood Compatibility
How to get Nonthrombogenic Surfaces?
There have been many efforts directed at obtaining
nonthrombogenic materials. The empirical approach has been used
often. These approaches can be categorized as
1. heparinized (negative charge),
Heparin is a polysaccharide with negative charges due to the sulfate
groups as shown
This method is to prepare heparin solution in which the implant
could be immersed followed by drying.
2. biological surfaces
Some studies were carried out to coat the cardiovascular implant
surface with other bio logical molecules such as albumin, gelatin
(denatured collagen), and heparin. Some reported that the albumin
alone can be thromboresistant and decrease platelet adhesion.

Blood Compatibility
2. Inert surfaces,
Hydrogels of both hydroxyethylmethacrylate (poly-HEMA) and acrylamide are
classified as inert materials since they contain neither highly negative anionic
radical groups nor are negatively charged. These coatings tend to be washed away
when exposed to the bloodstream
3. Solution-perfused surfaces.
Another method of making surfaces nonthrombogenic is perfusion of water (saline
solution) through the interstices of a porous material that interfaces with blood.
This new approach to a nonthrombogenic surface has the advantage of avoiding
damage to formed elements of the blood. The disadvantage is the dilution of
blood plasma. This is not a serious problem since saline solution is deliberately
injected for the kidney and heart/lung machine; the method can be used only in
such temporary blood-interfacing applications.

Wound Healing
What is wound?
What is wound healing?
Wound healing is a process in which epithelial, endothelial, inflammatory cells,
platelets and fibroblasts briefly come together outside their normal domains, interact
to restore a semblance of their usual discipline and having done to resume their
normal function.
Effects of implantation
The implantation of any biomaterial causes damage to the host tissue and inevitable
inflammation. The consequences of tissue damage during surgery must be
distinguished from those due to the implant. Persistent tissue changes, which are due
to the presence of the material, may be produced either mechanically or chemically.
These changes must be understood so that they may be controlled and manipulated
for a particular application. Wound healing and inflammation are controlled by effects
in the connective tissue, which carries the blood supply. Without an adequate blood
supply there is no wound healing. To understand the way in which tissues respond to
an implant, it is first necessary to understand the normal wound healing process.

Wound Healing-Definitions
Inflammation The condition produced by tissue damage, characterised by redness,
warmth, tension and pain.
Phagocyte Any cell that can ingest foreign material.
Microphage Small cells (3–5µm) that engulf small particles such as bacteria,
macromolecules or tissue fragments. They are more commonly called polymorphs.
Macrophages Larger cells (10–12 µm) that can engulf, digest and transport larger
particles than can a polymorph. The macrophage derives from a different leucocyte (a
monocyte), which moves from blood vessels into the tissues.
Giant cells Very large cells (40–100 µm), which form in connective tissue when the
material to be removed is too large for individual macrophages. They are formed
when many macrophages are crowded together and undergo mutual dissolution of
their cell walls to form a large syncytium of cells. Giant cells may have several hundred
nuclei and are often seen on a rough surface in a futile attempt to digest surface
irregularities. Giant cells have a relatively short life and cannot reproduce, so their
presence some time after implantation is a sign of an unwanted, persistent effect.

Wound Healing-Presence of Implants
Cellular Response to Implants
Generally the body reacts to foreign materials in ways to get rid of them. The foreign
material could be extruded from the body if it can be moved (as in the case of a wood
splinter), or walled-off if it cannot be extracted.
If the material is particulate or fluid, it will be ingested by giant cells (macrophages)
and removed. These responses are related to the healing process of a wound where
an implant is added as an additional factor. A typical tissue response is that the
polymorphonuclear leukocytes appear near the implant followed by the
macrophages, called foreign body giant cells.
However, if the implant is chemically and physically inert to the tissue, the foreign
body giant cells may not form. Instead, only a thin layer of collagenous tissue
encapsulates the implant.
If the material is bioactive, an adherent interfacial bond occurs and there is minimal, if
any, encapsulation. Bioactive glasses are examples of such materials.
If the implant is either a chemical or a physical irritant to the surrounding tissue,
inflammation occurs in the implant site. The inflammation (both acute and chronic)
will delay the normal healing process, resulting in granular tissues.
Some implants may cause necrosis of tissues by chemical, mechanical, and thermal
trauma.

Healing of Bone Fracture
The healing of bone fracture is regenerative rather than simple repair. The only other
tissue that truly regenerates in humans is liver.

Application of Protein Adsorption
Biological responses to implanted synthetic biomaterials that often impair their
usefulness, including the clotting of blood and the foreign body reaction.
Clearly, the body does recognize and respond to these types of biomaterials. The basis
for these reactions is the adsorption of adhesion proteins to the surface of the
biomaterials that are recognized by the integrin receptors present on most cells. The
adsorption of adhesion proteins to the biomaterial converts it into a biologically
recognizable material, as illustrated in Fig. The protein adsorption event is rapid
(seconds) and generally happens on all materials implanted into biological systems
with few exceptions.

Protein Adsorption
 In as short a time as can be measured after implantation in a living system (< 1
second), proteins are already observed on biomaterial surfaces. In seconds to
minutes, a monolayer of protein adsorbs to most surfaces.
 The protein adsorption event occurs well before cells arrive at the surface.
Therefore, cells see primarily a protein layer, rather than the actual surface of the
biomaterial.
 Since cells respond specifically to proteins, this interfacial protein film may be the
event that controls subsequent bioreaction to implants.
 Protein adsorption is also of concern for biosensors, immunoassays, array
diagnostics, marine fouling and a host of other phenomenon.
 After proteins adsorb, cells arrive at an implant surface propelled by diffusive,
convective or active (locomotion) mechanisms. The cells can adhere, release
active compounds, recruit other cells, grow in size, replicate and die. These
processes often occur in response to the proteins on the surface.
 After cells arrive and interact at implant surfaces, they may differentiate, multiply,
communicate with other cell types and organize themselves in into tissues
comprised of one or more cell types.

Protein Adsorption
Early biomaterials included many natural materials, whereas their modern
counterparts encompass man-made materials such as metals, ceramics, and synthetic
polymers. These foreign materials elicit responses from the body. Proteins play an
important role in this response, as a protein layer is deposited at the interfacial
surfaces within seconds of material introduction, a process defined as adsorption.
Protein adsorption is not necessarily an active response of the body to a material,
but it is often due to the presence of an abundance of proteins within body fluids
(BFs). Over long time periods, protein adsorption can lead to inflammatory responses
including foreign body giant cell formation and fibrous encapsulation of the
biomaterial.
Biological
Fixation
Morphological
Fixation

Protein Adsorption
Size of the protein – Larger molecular size provides more contact points during
adsorption on the surface.
Surface charge of the protein – Proteins adsorb more at/ or near the Isoelectric point.
Charged surfaces often interact favorably with proteins as most proteins are charged.
Structural stability of protein – Less stable proteins (those having less intra-molecular
cross linking) tends to unfold more providing more contact points on the solid surface.
Rate of unfolding – Proteins that undergo rapid unfolding make swift contacts or
adsorb quickly
Concerning the nature of solid surfaces, there are some factors which particularly
influence the adsorption event
Surface topography – Higher surface area provides more interaction for the protein.
Surface composition – Surface chemical composition determines the nature of
intermolecular forces involved at contact point(s) leading to the interaction process.
Hydrophobicity of surfaces – More hydrophobicity normally allows more protein
molecules to bind

Application of Protein Adsorption
Depending on the application, protein adsorption can be desirable or inhibitory; the
choice is related to what is required of the biomaterial and the physiological response
that it elicits.
For example, protein adsorption on cardiovascular grafts is generally undesirable.
Thus, polytetrafluoroethylene, which inhibits adsorption because of its high
hydrophobicity, has been successfully used in vascular grafts.
In addition, protein adsorption is generally not advantageous in certain drug delivery
methods. PEG has been widely used to bestow “stealthiness” to drugs circulating in
the blood because its hydrophilicity renders the surface resistant to protein
adsorption, thus delaying its clearance by the liver and kidney.
Conversely, in specific tissue-engineering applications, protein adsorption is
encouraged. Numerous tissue-engineering efforts employ the modification of a
biomaterial’s surface with proteins such as collagen, fibronectin, and laminin to
promote protein adsorption. Polymers can be used in a diverse range of areas
including biologically inspired systems

Bone Healing Types and Stages
Bone healing is an intricate regenerative process which can be
classified into
 Primary (direct) bone healing
 Secondary (indirect) bone healing

Direct/ primary healing
 Bony fragments are fixed together with compression.
 There is no callus formation.
 The bony ends are joined and healed by osteoclast and
osteoblast activity
 Requires reduction of the fracture ends, without any gap
formation, as well as stable fixation. Thus, it does not
usually occur naturally but rather following open reduction
and internal fixation surgery
 Direct bone healing can occur by direct remodeling of
lamellar bone, the Haversian canals, and blood vessels.
 The process usually takes from months to years.
 Primary healing of fractures occurs through:
•Contact healing
•Gap healing.

Indirect healing
 More common than direct healing
 Anatomical reduction and stable conditions are not required for
indirect healing to occur. Rather, there is a small amount of motion
and weight-bearing at the fracture, which causes a soft callus to
form, leading on to secondary bone formation.
 It should be noted though that too much load/movement can result
in delayed healing or non-union, which occurs in 5-10% of all
fractures
Secondary bone healing can be divided into four stages:
• Inflammation
• Soft callus formation
• Hard callus formation
• Remodelling

Indirect healing occurs with:
 Non-operative fracture treatment
 Operative treatments where some motion occurs at the
fracture site, such as:
 Intramedullary nailing
 Internal fixation of
comminuted fractures
 External fixation

Stages of fracture repair-Indirect
•After fracture, the inflammatory process starts rapidly and lasts until fibrous tissue,
cartilage, or bone formation begins (1–7 days of postfracture).
•Initially, there is hematoma and inflammatory exudation formation from ruptured
blood vessels. Hematoma is accumulation of blood outside of blood vessels due to
rupture.
•Bone necrosis is seen at the ends of the fracture fragments.
•The fracture hematoma is gradually replaced by granulation tissue.
•Osteoclasts in this environment remove necrotic bone at the fragment ends.
Inflammation

Stages of fracture repair--Indirect
Eventually, pain and swelling decrease and soft callus is formed.
Soft callus composed of fibrous tissues and cartilage replaces the
blood clot at the fracture site. This callus holds the pieces of
fractured bone together, but it’s vulnerable. It’s not strong enough
to be used in the way that bone would be used.
This corresponds roughly to the time when the fragments are no
longer moving freely, approximately 2–3 weeks postfracture.
Soft callus formation

Hard callus formation
When the fracture ends are linked together by soft callus, the
hard callus stage starts and lasts until the fragments are firmly
united by new bone (3–4 months).
Eventually, as healing continues, the soft callus develops into a
hard callus. The hard callus is actually bone, but it’s still softer
than regular bone.

The remodeling stage begins once the fracture has solidly united
with woven bone. The woven bone is then slowly replaced by
lamellar bone through surface erosion and osteonal remodeling.
This process may take anything from a few months to several years.
It lasts until the bone has completely returned to its original
morphology, including restoration of the medullary canal.
Remodelling

Fracture Fixation
 For a fracture to heal properly, the bone ends must be aligned and stabilized.
 Stabilization may be accomplished externally, as with a cast, or internally (surgically), with
screws, plates, pins, or rods.
 Design principles, selection of materials, and manufacturing criteria for orthopedic implants
are the same as for any other engineering products undergoing dynamic loading.
 Although it is tempting to duplicate the natural tissues with materials having the same
strength and shape, this is not practical since the natural tissues and organs have one major
advantage over man-made implants, that is, their ability to adjust to a new set of
circumstances by remodeling their micro- and macrostructure in response to prevailing
stress conditions, and to repair damage. Consequently, the mechanical fatigue of tissues is
minimal unless a disease hinders the natural healing processes or unless they are
overloaded beyond their ability to heal.
 It is logical that bone repairs should be made according to the best repair course that the
tissues themselves follow. There fore, if the bone heals faster when a compressive force (or
strain) is exerted, we should provide compression through an appropriate implant design.
Equilibrium between osteogenic and osteoclastic activities is governed according to the
static and dynamic force applied in vivo, that is, if more load is applied the equilibrium tilts
toward more osteogenic activity to better support the load and vice versa (Wolff's law),
 Of course, excessive load should not be imposed by the implant; too much force can
damage the cells rather than enhance their activities.

Fracture Fixation
 The basic goal of fracture fixation is to stabilize the fractured bone, to enable fast
healing of the injured bone, and to return early mobility and full function of the
injured extremity.
 Fractures can be treated conservatively or with external and internal fixation.
 Non-surgical treatments: Immobilization with cast (plaster or resin) or with
plastic brace.
 Surgical treatments
•External fixation
Does not require opening the fracture site.
Bone fragments are aligned by pins placed through the skin onto the skeleton
Structurally supported by external bars.
•Internal fracture fixation
Requires opening the fracture site.
The bone fragment are held by wires, screws, plates, and/or intramedullary
devices.

WIRES, PINS, AND SCREWS
Wires
 The simplest but most versatile implants are the various metal wires (diameter
<2.38 mm) and Steinmann pins for those of larger diameter), which can be used
to hold fragments of bones together. Wires can be monofilament or
multifilament.
 Used to reattach the greater trochanter in hip joint replacements or for long
oblique or spiral fracture of long bones.
 The common problems of fatigue combined with corrosion of metals may
weaken the wires in vivo. The added necessity of twisting and knotting the wires
for fastening aggravates the problem since strength can be reduced by 25% or
more due to the stress concentration effect. The deformed region of the wire
will be more prone to corrosion than the undeformed region due to the higher
strain energy.
 A knot requires the wire to be flexed, folded and twisted. This creates changes in
the outer and inner circumference of the fold/twist and thus causing stress on
the wire. When put in tension, this difference in stress across the wire’s
diameter results in reduction of strength and can cause breakage if loaded
beyond reduced breaking strength.

Pins
 The Steinmann pin is also a versatile implant often used for internal fixation in
cases when it is difficult to use a plate or when adequate stability cannot be
obtained by other means.
 Three types of tip designs are shown in Figure. The trochar tip is the most
efficient in cutting; hence, it is often used for cortical bone insertion. The
fractured bones can be held together by two or more pins inserted
percutaneously away from the fracture site, and the pins are fixed by a device
such as the Hoffmann external fixator shown in Figure
Hoffman external long-bone fracture fixation device:
(a) external view, (b) x-ray view

Screws
Screws are some of the most widely used devices for fixation of
bone fragments to each other or in conjunction with fracture
plates.
There are basically two types of screws: one is self-tapping and the
other non-self-tapping
 A self-tapping screw cuts its own threads as
it is screwed in
 The extra step of tapping (i.e., cutting
threads in the bone) required of the non-
self-tapping screws make them less
favorable, although the holding power (or
pull out strength) of the two types of screws
is about the same.

Screws
The variations in thread design do not influence holding power.
However, the radial stress transfer between the screw thread and
bone is slightly less for V-shaped thread than buttress thread,
indicating that the latter can withstand longitudinal load better.
 The pull-out strength or holding strength of
screws is an important factor in the selection
of a particular screw design.
 However, regardless of the differences in
design, the pull-out strength depends only
on the size (diameter) of the screw, The
larger screw, of course, has a higher pull-out
strength.

Cortical Screw Cancellus Screw Cannulated Screw
Partially threaded Screw
Locking screw

Fracture Plates
 There are many different types and sizes of
fracture plates
 Since the forces generated by the muscles in
the limbs are very large, generating large
bending moments, the plates must be
strong. This is especially true for the femoral
and tibial plates.
 In comparison with the bending moment
at the proximal end of the femur during
normal activities (24-126 N-m), one can
see that the plates cannot withstand the
maximum bending moment applied.
Therefore, some type of restriction on the
patient's movement is essential in the
early stages of healing.

Fracture Plates
Surgical considerations
 Adequate fixation of the plate to the bone with the screws is
important
 Overtightening may result in necrosed bone as well as deformed
screws which may fail later due to the corrosion process at the
deformed region
Functions
 The plate produces compression at the fracture site to produce
absolute stability
 Provide stability by fixation of two main fragments achieving
correct length, alignment and rotation

Fracture Plates-Dynamic Compression Plate
Principle
New design of the compression plate
is based on a screw hole design which
permits a sliding and a compressive
movement during operation.
Screw head slides down the inclined
plate hole as it is tightened, forcing
the plate to move along the bone and
compressing the fracture

Fracture Plates-Dynamic Compression Plate
 The added complexity of the devices and the controversy as to
whether the compressive forces or strain is beneficial had hindered
early acceptance of the devices.
 It is interesting to note that traditionally a large amount of callus
formation has been considered to be a favorable sign and even
essential for good healing.
 However, with the use of the compression plate, the opposite is
thought to be a more favorable sign of healing. In this situation the
amount of callus formed is proportional to the amount of motion
between plate and bone.

Fracture Plates
Drawbacks
 One major drawback of healing by rigid plate fixation is weakening of
the underlying bone such that refracture may occur following
removal of the plate. This is largely due the stress-shield effect upon
the bone underneath the rigid plate. The stiff plate can carry so much
of the load that the bone is under stressed, so that it is reabsorbed by
the body according to Wolff's law.
 In addition, the tightening of the screws that hold the bone plate
creates a concentrated stress upon the bone; this can have a
deleterious effect if the screws are in cancellous bone- Necrosis.
 Measures: resorbable bone plates made of poly-l-glycolic acid (PLGA)
have been tried experimentally.
 Challenges: Difficult-
1. to achieve uniform resorption of this kind of implant
2. to achieve the correct rate of resorption
3. to make sufficiently strong screws from this type of material.

Metallic biomaterials
• Metallic biomaterials are used almost exclusively
for load bearing applications
Applications
- Bone and Joint Replacement
- Dental Implants
- Maxillo and Cranio/facial reconstruction
- Cardiovascular devices

Design Considerations
 Typically want to match mechanical properties of tissue
with mechanical properties of metal
 Have to consider how the metal may fail in vivo
 Corrosion
 Wear
 Fatigue
 Cost

Ion
Normal concentration
range (mmol.L−1)
Sodium 135–145
Potassium 3.6–5.1
Chloride 95–105
Calcium 2.1–2.8

Metallic Biomaterials
302 and 316 stainless steel are both types of austenitic stainless steel, which is a
type of alloy that is highly corrosion-resistant, non-magnetic, and has good
formability and weldability. The main differences between 302 and 316 stainless
steel are their chemical composition, their corrosion resistance.
Chemical Composition:
• 302 stainless steel contains 18% chromium and 8% nickel
• 316 stainless steel contains 16% to 18% chromium, 10% to 14% nickel, and 2% to
3% molybdenum.
Corrosion Resistance:
•316 stainless steel is more resistant to corrosion than 302 stainless steel, due to the
addition of molybdenum, which improves the steel's resistance to pitting corrosion
and other forms of corrosion.
Carbon content of 316 stainless steel was reduced from 0.08 wt% to 0.03 wt%
maximum for better corrosion resistance, and it became known as 316L, which is
most commonly used in biometal.

Functions of Cr and Ni in 316L
 The key function of chromium is to permit
the development of corrosion-resistant
steel by forming a strongly adherent
surface oxide (Cr2O3).
 However, the downside to adding Cr is
that it tends to stabilize the ferritic (BCC,
body-centered cubic) phase of iron and
steel, which is weaker than the austenitic
(FCC, face-centered cubic) phase.
 Moreover, molybdenum and silicon are
also ferrite stabilizers. So to counter this
tendency to form weaker ferrite, nickel is
added to stabilize the stronger austenitic
phase.

If C content is high in 316L !
 The main reason for the low carbon
content in 316L is to improve corrosion
resistance.
 If the carbon content of the steel
significantly exceeds 0.03%, there is
increased danger of formation of
carbide, Cr23C6. Such carbides have the
bad habit of tending to precipitate at
grain boundaries when the carbon
concentration and thermal history are
favorable to the kinetics of carbide
growth.
 The negative effect of carbide precipitation is that it depletes the adjacent grain boundary
regions of chromium, which in turn has the effect of diminishing formation of the
protective, chromium-based oxide Cr2O3.
 Steels in which such grain-boundary carbides have formed are called “sensitized” and are
prone to fail through corrosion assisted fractures that originate at the sensitized
(weakened) grain boundaries.

Processing of stainless steel
 Cold Rolling  Hot rolling
 Casting  Annealing

Concerns related to processing of stainless steel
 The austenitic stainless steels work-harden very rapidly, and therefore cannot
be cold-worked without intermediate heat-treatments.
 The heat-treatments, however, should not induce formation of chromium
carbide (CCr4 ) in grain boundaries, which might deplete Cr and C in the grains,
causing corrosion. For the same reason, austenitic stainless steel implants are
not usually welded.
 Another undesirable effect of heat-treatment is the formation of surface oxide
scales that have to be removed either chemically (acid) or mechanically
(sandblasting). After the scales are removed the surface of the component is
polished to a mirror or matte finish. The surface is then cleaned, degreased, and
passivated in nitric acid (ASTM Standard F86). The component is washed and
cleaned again before packaging and sterilizing.

Metallic Biomaterials- Co-Cr alloy
1. CoCrMo alloy: Which is usually used to cast a product. It has been in use for many
decades in dentistry and in making artificial joints.
2. CoNiCrMo alloy: Which is usually wrought by (hot) forging. It has been used for
making the stems of prostheses for heavily loaded joints (such as the knee and hip).
The superior fatigue and ultimate tensile strength of the wrought CoNiCrMo alloy
make it very suitable for applications that require a long service life without fracture
or stress fatigue. Such is the case for the stems of the hip joint prostheses. This
advantage is more appreciated when the implant has to be replaced with another
one since it is quite difficult to remove the failed piece of implant embedded deep in
the femoral medullary canal. Furthermore, the revision arthroplasty is usually
inferior to the original in terms of its function due to poorer fixation of the implant.
Molybdenum is added to produce finer grains, which results in higher strength after
casting or forging.

Processing of CoCr alloy
 The CoCrMo alloy is particularly susceptible to the work-hardening so that the
normal fabrication procedure used with other metals cannot be employed.
 Instead the alloy is cast by a lost wax (or investment casting) method that
involves the following steps
Investment casting-process
 A wax pattern of the desired component is made.
 The pattern is coated with a refractory material, first by a thin coating with a
slurry (suspension of silica in ethyl silicate solution) followed by complete
investing after drying.
 The wax is melted out in a furnace (100–150°C).
 The mold is heated to a high temperature, burning out any traces of wax or gas-
forming materials.
 Molten alloy is poured with gravitational or centrifugal force. The mold
temperature is about 800–1000°C and the alloy is at 1350–1400°C.

Processing of CoCr alloy-Investment casting

Processing of CoCr alloy- Investment casting
Lost wax casting of femoral joint prosthesis. (a) Injection of wax into a brass mold. (b) Wax
patterns assembled for a ceramic coating (note the hollow part of the femoral head). (c)
Application of ceramic coating. (d) A hot pressure chamber retrieves the wax, leaving
behind a ceramic coating. (e) Pouring molten metals into the preheated ceramic mold.
e

Concerns related to processing of Co-Cr alloy
 Because of non-equilibrium cooling, a “cored” microstructure can develop. In this
situation, the interdendritic regions become solute (Cr, Mo, C) rich, while the
dendrites become depleted in Cr and richer in Co. This is an unfavorable electro
chemical situation, with the Cr-depleted regions being anodic with respect to the
rest of the microstructure. Solution- Subsequent solution anneal heat
treatments at 1225°C for 1 hour can help alleviate this situation.
 Controlling the mold temperature will have
an effect on the grain size of the final cast;
coarse ones are formed at higher
temperatures. This is generally undesirable
because it decreases the yield strength via a
Hall–Petch relationship between yield
strength and grain diameter. Solution-
Powder Metallurgy
 Cast microstructure may consists of grain
boundary carbides (M23C6) at high processing
temperature. Solution- Controlled Temp

 Solution- Powder metallurgy
 Casting defects may arise. Figure shows an
inclusion in the middle of a femoral hip stem.
The inclusion was a particle of the ceramic
mold (investment) material, which
presumably broke off and became entrapped
within the interior of the mold while the
metal was solidifying. This contributed to a
fatigue fracture of the implant device in vivo,
most likely because of stress concentrations
and crack initiation sites associated with the
ceramic inclusion.
 For similar reasons, it is also desirable to
avoid macro- and microporosity arising from
metal shrinkage upon solidification of
castings.

 Again, according to a Hall–Petch relationship, this microstructure gives the alloy
higher yield strength and better ultimate and fatigue properties than the as-cast
alloy. Generally speaking, the improved properties of the HIP versus cast F75
result from both the finer grain size and a finer distribution of carbides, which
has a hardening effect as well
 To avoid problems such as the above with
cast alloy, and to improve the alloy’s
microstructure and mechanical properties,
powder metallurgical techniques have been
used. For example, in hot isostatic pressing
(HIP), a fine powder of the alloy is
compacted and sintered together under
appropriate pressure and temperature
conditions (about 100 MPa at 1100◦C for 1
hour) and then forged to final shape. The
typical microstructure (Fig. 8) shows a much
smaller grain size (∼8 µm) than the as-cast
material.

Metallic Biomaterials-Ti alloy
Aluminum stabilizes α phase (HCP), i.e
increases the α-β transformation temp
Phase diagram of Ti-Al-V at 4 wt% V
Phase diagram of Ti-Al-V at 6 wt% Al
Ti alloys are used in hip joints, bone screws, knee joints, bone plates, dental
implants, surgical devices due to its resistance to attack by body fluids, low density,
high strength and low modulus.
Commercially Pure (CP Ti) and Ti6Al4V alloy: Corrosion resistance comes from TiO2.
Titanium is an allotropic material that exists as HCP up to 882°C and BCC above that
temperature. The addition of alloying elements to titanium enables it to have a wide
range of properties:
β stabilizers are highly effective in improving strength by heat treatment
Vanadium stabilizes β phase (BCC), i.e
lowering the α-β transformation temp

Concerns related to processing of Ti alloy
 Titanium is very reactive at high temperature and burns readily in the presence
of oxygen. Solution- requires an inert atmosphere for high-temperature
processing or is processed by vacuum melting
 Oxygen diffuses readily in titanium, and the dissolved oxygen embrittles the
metal. Solution- hot-working or forging operation should be carried out below
925°C
 α alloys have single-phase microstructure, which promotes good weldability. The
stabilizing effect of the high aluminum content of these groups of alloys makes
for excellent strength characteristics and oxidation resistance at high
temperature (300–600°C). These alloys cannot be heat-treated for strengthening
since they are single phased since the precipitation of the second or third phase
increases the strength by precipitation hardening process.

Concerns related to processing of Ti alloy
 The addition of controlled amounts of β-stabilizers causes the higher strength
phase to persist below the transformation temperature, which results in the
two-phase system. the precipitates of β phase will appear by heat-treatment in
the solid solution temperature and subsequent quenching, followed by aging at
a somewhat lower temperature.
Single phase Dual phase Dual phase

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