Worksheet1

Biomaterial and Implants

Practice Questions
1. Biomaterials
(a) are always synthetic materials; natural materials are not employed
(b) are always natural materials; synthetic materials are not employed
(c) can be natural or synthetic materials
(d) are always polymeric materials
2. Select the statement which correctly relates to biocompatibility.
(a) a biocompatible material should provide healing characters
(b) a biocompatible material should have therapeutic characteristics
(c) a material is considered as a biocompatible material as long as it
causes no harm to the host body
(d) a biocompatible material should have the exact dimensions as the
damaged tissue or part
3. Select the option(s) which do(es) NOT come under the class of bio-
compatible materials.
(a) eyeglasses; wheelchair
(b) contact lenses; dental implants
(c) orthopedic implant; stents
(d) external hip prosthesis; massage footwear
4. Which of the following has the best osteointegration properties?
(a) SS316
(b) porous titanium
(c) Co-Cr alloys
(d) all of the above
5. Which of the following is/are biomaterial(s)?
I. materials used for tooth filling
II.materials used for cardiovascular repairs
III. glucose meters and stethoscopes
IV. materials used for hip implants
(a) only I
(b) only I, II and IV
(c) only I, III and IV
(d) only III
6. Select the option(s) which is/are TRUE about biodegradation.
(a) it depends on the molecular architecture
(b) it is a precise breakdown of the material over time
(c) metals biodegrade faster than polymeric materials
(d) all of the above
7. Which class of biomaterials has chemical structures similar to bone?
(a) polymeric biomaterials
(b) ceramic biomaterials
(c) metallic biomaterials
(d) all of the above
8. Which class of biomaterials encourages bonding with surrounding tissues and stimulates new bone
growth?
(a) bioinert ceramics
(b) bioactive ceramics
(c) Co-Cr alloys
(d) all of the above
9. Which of the following is TRUE?
(a) ceramics possess excellent wear and friction properties
(b) SS316, Co-Cr and Ti alloys form a protective oxide layer on their surfaces
(c) bioceramics are more reactive then certain metallic implants
all of the above
Questions with Solutions
1. Give three examples of biomaterials or devices for each: (a) the first, (b) the second and (c) third
generation. Indicate the focus of each of these evolving phases.
a) Some examples of first generation biomaterials included stainless steel fracture plates and screws,
alumina (ceramic) acetabular cups, and PMMA (acrylic) bone cement. For first generation
biomaterials, the goal was to achieve bio inertness. That is, materials were selected based on their
physical properties so to match the functional properties of the tissues. Materials selected were known
to undergo minimal interaction with the body in vivo.
b) Second generation biomaterials included hydroxyapatite coatings, biodegradable polymers such as
polylactide (PLA), and hydrogels such as poly(2-hydroxyethyl-methacrylate) (PHEMA). The purpose
of using these biomaterials was to achieve some level of bioactivity to promote some desired biological
response.
c) The focus of the latest, 3rd generation of biomaterials is to achieve specific cellular responses
through both bioactive and biodegradable means with the intent of regenerating functional tissue. For
instance, 3D scaffolds are being employed for tissue engineering applications. Different biomaterials
being used for this application include natural polymers like collagen, composite materials
incorporating different classes of biomaterials such as hydrogels loaded with CaP particles in
suspension, and even porous, bioresorbable magnesium scaffolds.
2. List important requirements (at least 5) to qualify materials for in vivo use.
1. The material must perform its desired function effectively.
2. The material must be biocompatible in the sense that it does not harm the patient.

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 3. The material must have the desired physical characteristics to survive throughout the expected
implant lifetime.
4. The material must be able to undergo manufacturing to shape it into the final implant form.
5. The material must be able to undergo sterilization.
3. Give two pairs of new examples (different from those used in problem 1) of materials used in medical
devices, one of each pair being a biomaterial of interest to the biomaterials scientific community and the
other non-biomaterial but biomedical material. The two examples of each pair must be used in the
treatments for the clinical issues of the same organs or tissues (e.g. contact lenses and glasses). You are
encouraged to search on the internet, and you may use images to illustrate your answer but refer to the
figures with a short description. If using online materials provide source or citation.
Examples: Knee Prosthesis and Knee Brace, Artificial Skin and Bandages Additional examples with
pictures below:

4. You have two metal specimens both of which are cylindrical with a diameter of 10 mm and length of
220 mm. One is made of titanium alloy (E = 100 GPa) and the other of stainless steel (E = 200 GPa). Both

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of them are subjected to a tensile force of 600 N. Which of them will have higher stress? Which will develop
higher strain? Given the information provided can you tell which of the specimens will be stronger?
Both specimens will have the same stress applied on them:

In order to determine which specimen is stronger, the ultimate tensile strength is needed. Because this
information is not provided as a value or as part of a stress-strain curve, one cannot tell which specimen
will be stronger.
5. For each of the following materials, select the type of stress-strain curve shown in the figure that best
describes it.
a) Ceramics and glasses. Hard-brittle
b) Polymers such as polyethylene (used in articulation applications). Ductile-tough
c) Glassy polymers such as poly (methyl methacrylate) Hard-brittle
d) Soft tissues such as skin, blood vessel walls, etc. Ductile-soft
e) Hard mineral tissues such as bone and teeth. Ductile-tough
f) Rubber band (elastomer). Ductile-soft
g) Zirconia and alumina. Hard-brittle
h) Cobalt chromium and steels. Ductile-tough

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 Figure: Stress strain graph
6. The following data was obtained using a stainless steel tensile specimen:

a) Plot the stress-strain curve.

b) Determine the modulus of elasticity, the yield strength, the ultimate strength, the toughness, the
resilience, the fracture strength and ductility.

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b)
Modulus of Elasticity: 1.8 GPa
Yield Strength: 350 MPa
Ultimate Strength: 930 MPa
Toughness: 240.25 MPa
Resilience: 34.03 MPa
Fracture Strength: 930 MPa
Ductility: 80% Calculations for each part will be shown in P7.

7. From the fatigue data shown below:

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8. Give examples of device applications (2-3) where: (a) hydrophilic surfaces and (b) hydrophobic surfaces
would be indicated. Provide a rationale for each of your choices.
a) Examples of device applications incorporating hydrophilic surfaces include contact lenses, titanium
dental implants for Osseo integration and neural implants to mitigate biofouling and implant rejection.

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b) Examples of device applications using hydrophobic surfaces include microelectromechanical-system
(MEMS) or any other component of a device that requires sealing to prevent fluids from penetrating it.
9. The following data were obtained using unknown liquids and a polyethylene sheet.

a. Plot the interfacial surface tension versus contact angle.

b. Obtain a linear relationship between interfacial surface tension and contact angle. Obtain the linear
relationship by creating a linear trend line for the points.

10. Summarize the main characteristics that qualify a metallic material for in vivo implantation.
The main characteristics that qualify a metallic material for in vivo implantations are:

• High Corrosion Resistance: the ability to have a high oxide layer to prevent corrosion of tissues
around the material.
• Biocompatibility: to minimize harmful and adverse host reactions.
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 • Matching Mechanical Properties: to mimic mechanical properties of the tissue or organ being
replaced.
• High Wear Resistance: to help the reduction of inflammation by minimizing the amount of metal
ions being released to nearby tissues.
11. Select the description(s) that correctly define biocompatibility:
Answer: (c) and (d) all or nothing.
(a) The ability to heal an injured or diseased organ or tissue.
(b)The capacity to encourage damaged tissue to regenerate.
(c) It is not about therapeutic performance. A material is considered to be biocompatible as long as it has
no harm on the host body.
(d) Biocompatibility of a medical device covers both the compatibility of the materials used and how the
device has been engineered (e.g. geometric, mechanic, electric properties).
(e) Therapeutic function.
Another definition is the ability to be in contact without producing an adverse effect, but does not
necessarily mean it will provide healing characteristics. Therefore, by this definition it rules out answers
(a), (b), and (e)
12. Which material(s) in the following medical devices is classified as a biomaterial?

Answer: (c) and (b), Review slides for definitions and examples of biomaterials
13. Briefly describe one of the biomaterials technology discussed in “Biomaterials and Bioengineering
Tomorrow’s Healthcare”.

• What is the biomaterial technology (make-up as well)?

• What is its use?
• How has the biomaterial changed or evolved?
14. You are given two samples of the same polymer. One is atactic and the other is isotactic. Which will be
more difficult to dissolve in a solvent and why?
One would expect the mostly crystalline (isotactic) polymer to be more difficult to dissolve in a solvent due
to its greater structural organization and packing of the polymer chains. On the other hand, an amorphous

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(atactic) polymer would contain more gaps in its structure due to the random orientation of its side chains
and hence would be easier to dissolve.
15. Explain the difference between branched and cross-linked polymers. Which would be expected to be
stiffer? Why?
Branched polymers are the way a polymer is organized, and they have small side chains extending from
the polymer backbone. Branching occurs when side reactions are present and chains (different from the
main backbone) are added to the growing polymeric backbone chain. Cross-linked polymers are a network
of polymer chains covalently bonded to one another. The cross-linked polymers are expected to be stiffer
because they require more energy to break, or disrupt the covalent bonds as opposed to the branched
polymers.
16. Explain the effect of crosslinking on the thermal behavior of a polymer.
Crosslinking creates chemical bonds between the chains. Therefore, increasing the cross-link density
increases the amount of chemical bonds to disrupt, which would require more energy thus a higher
temperature.
17. List the factors affecting the Tg of an amorphous polymer.

• Chemical Structure: double bonds (backbone flexibility), bulky pendant groups, restrict rotation
increase Tg
• Molecular Weight: higher MW leads to increase in Tg
• Plasticizers: reduce Tg by increasing free volume
18. Discuss some of the issues associated with bone cements. Explain the mechanism of cure of
commercial bone cements.
Issues:

• Viscosity levels
• Plasticization
• Shrinkage
• Free radical polymerization is exothermic reaction
The mechanism of curing of commercial bone cements is mixing the polymer powder and liquid monomer
through free radical polymerization. Set time can be altered to provide the medium needed for a certain
application.
19. List advantages and disadvantages of UHMWPE and summarize the characteristics of different
generations of this material.
Advantages

• High yield
• Low wear rates
• Good wear resistance
Disadvantages

• Decreased ductility
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 • Fracture toughness
• Expensive and complicated to process
• Can shed particles if not cross-linked correctly
First Generation: easily damaged, sheds particles
Second Generation: reduced wear and increased mechanical properties by cross linking
Third Generation: removed free radicals through annealing
Fourth Generation: introduced quenching after annealing of free radicals, introduced Vit-E to also
improve mechanical properties
20. Explain how oxidation can occur with polyethylene and what properties are affected by this process.
Oxidation occurs when the polyethylene undergoes cross-linking and free radicals are left, that weren’t
covalently bonded, open. Oxidation leads to a decrease in the polymers’ shelf life, decrease in elongation
to failure, increase in elastic modulus, and decrease in fatigue crack propagation resistance.
21. Describe the common feature and differences between polymers and the two other types of materials
studied (metals and ceramics) in terms of building blocks and networks
Metals are typically bonded through metallic bonds, in which electrons are shared. They are highly
crystalline, dense, and have elastic and plastic regions of deformation. They are strong, have high elastic
moduli, but not as hard as ceramics. They are often reactive and form surface oxides that provide many of
the chemical properties that allow for metal use in vivo. Ceramics are typically formed through covalent
bonds that are polar, or ionic bonds in some cases. They have a highly crystalline structure that results in
ceramics possessing the highest modulus of all classes but also the most brittle behavior. They generally
perform well under compression and articulation, but poorly under tension compared to metals. While
ceramics often do not corrode and have poor osseointegration, they can be worked through a controlled
crystallization process to alter the chemical reactivity and become more suited for use in vivo. Polymers
are typically bonded with rigid C-C covalent bonds that are relatively nonpolar in nature. Polymers are
not very crystalline and thus have low modulus, and their mechanical properties are dependent largely on
the degree of crosslinking in the polymer. Also, they have the largest change in mechanical properties at
varying temperatures compared to ceramics and metals. Chemically, polymers can have a variety of
properties based on the side groups that are attached to the carbon backbone. They are often suitable for
use in vivo due to their degradability and ability to regulate integration through drug elution.
22. For the following questions read the following paper: (File name: Article for P. 22) Yang, Jian, et al.
"Synthesis and evaluation of poly (diol citrate) biodegradable elastomers." Biomaterials 27.9 (2006):
1889-1898
A. Describe the measurement of contact angle and how this paper uses this measurement to
characterize the described materials. Be sure to mention any correlation between polymer
structure and observed contact angle.
The contact angle was measured from equilibrium water-in-air angles of poly (diol citrate) films from 15°
to 53°. The initial contact angle increased when the hydrophobic methylene units in the diol monomer
increased or when MDEA was introduced. The addition of the MDEA resulted in a higher cross-linked
density so the density of the cross-links and the initial contact angle seem to have a positive correlation.

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After 25 minutes of contact time, the equilibrium water-in-air angles of poly (diol citrate) films have very
good wettability.
B. Describe the measurement of the glass transition temperature and provide a basic description of
what happens to polymer networks at the glass transition. What is the effect of polymer structure
on the observed Tg for the materials described here?
The glass transition temperature was measured by determining the middle of the recorded step change in
heat capacity from the second heating run. When a polymer undergoes its glass transition temperature the
amorphous solid to a viscous/rubbery state. In this paper, when the cross-links are increased, the chain
mobility was decreased, and the glass transition temperature increased as a result.
C. How was the initial biocompatibility of the material assessed? How did the authors arrive at the
conclusion that the synthesized materials are “cell and tissue-friendly”.
The biocompatibility of the material was addressed by implanting poly (diol citrate) it into Sprague-Dawley
rats and seeing the response. There was a slight inflammatory response for 1-week samples and samples
of the copolymer that were implanted for 1-4 months had a slight fibrous capsule around it. However, the
thickness of this did not increase. They arrived at the conclusion by determining that a mild inflammatory
response is expected when a foreign material enters the body. This was confirmed by their in vivo and in
vitro evaluation of the poly (diol citrate).
D. Describe the mechanism of degradation for the materials synthesized in this study.
The mechanism of degradation for the materials synthesized was done by using an equation of mass loss
as shown below:

This equation was implemented a-er the specimens were placed in a tube with 10ml phosphor buffer saline
to expedite the degradation process of the specimens. A-er incubation, the samples were washed and freeze-
dried for a week. They then compared the initial mass and the final mass by using the equation above.

Worksheet II
Biomaterial and Implants
Instruction: Please carefully read the below scenario on Synthetic pathways for a new
conjunctiva and provide a solution
The conjunctiva covers the exposed part of the opaque part of the eye (sclera) and the inner surface
of the eyelids. It is made up three tissue types. The epithelial tissue is stratified and contains
specialized cells (goblet cells) that synthesize and secrete mucus that contributes to the protective
and lubricating layer on the exposed surface of the eye. Underneath the epithelial tissue is a very
thin basement membrane and connected to it is the conjunctival stroma, a loose vascular supportive
tissue comprising extracellular matrix proteins and blood vessels. See Fig. 1.

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 Fig. 1: Conjunctiva of the eye
Wounds in the conjunctiva can be induced by chronic infection (trachoma) that remains untreated
(typically due to unavailability of medical care in certain developing economies). Such chronic
wounds can be deep, extending into the stroma and eventually closing by contraction and scar
formation, processes which block vision. Typically, one eye only is compromised by this
condition; however, both eyes may eventually also get involved.
You are working as a consultant in a medical device company that is interested in designing a
device to be used in inducing regeneration of the diseased conjunctiva. The device that you will
design will be placed in contact with a surgically induced full-thickness square wound, initially
measuring 2 x 2 mm2 in area, in the diseased conjunctiva. A successful device will induce
regeneration of all three tissues of the conjunctiva, with recovery of function in less than 8 weeks.
In your design consideration you will make the assumption that only one eye has been affected at
the time of treatment. Also assume that the conjunctiva has a morphology that is very similar
(though not identical) to that of the skin of a rodent. You will also assume that the full-thickness
conjunctival wound responds to regenerative treatment by a successfully selected device as if it
were a full thickness wound in the skin of a rodent. Obviously, approximating the conjunctival
wound with a skin wound is a first-order approximation that only serves as a screening tool, of
help in selecting a basic design strategy from among several strategies that have no chance of
providing a useful answer.
Listed below are various suggestions for potentially regenerative devices that have been made to
you by coworkers or suppliers of medical reagents or devices. For each suggestion, please provide
either a positive or negative response and provide a brief explanation for your selection. A negative
response implies that the suggestion has practically no chance of leading to a regenerated
conjunctiva (little or no efficacy) or that the suggestion comes with an unacceptably high cost to
the patient (little or no safety). A positive response does not guarantee success; however, it
suggests that the selection has the potential of eventually providing a useful device provided other
requirements are included in a future design (high efficacy) and that it is generally safe (high
safety).

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Your brief response for each selection should address both the efficacy and safety issues. Perfect
efficacy implies regeneration of all three conjunctival tissue types. If unsure about the safety of a
substance of device, you must conclude that the safety is not high and must be specifically tested
for.
A. An autologous cell culture comprising mature cells from the epithelial tissue layer of the
conjunctiva from the uninfected eye will be drizzled onto the surgically wounded conjunctiva at
the rate of about 2 million cells per day for a period of 14 days.
B. A porous copolymer of lactic acid/glycolic acid, comonomer ratio 75/25, that degrades with a
half-life of 14 days, average pore size 100 μm, with randomly oriented pore channels is grafted on
the wound.
C. A porous scaffold identical to that described in B above except seeded with 3 million epithelial
conjunctival cells, identical to cells described in A above, is grafted on the wound. The cells have
been seeded into the scaffold prior to grafting of the scaffold on the wound.
D. Continuous infusion into the wound over 14 days of a low-molecular weight substance X that
blocks the intracellular pathway responsible for synthesis of alpha smooth muscle actin by
fibroblasts. Substance X has been studied in vitro; no in vivo studies of X have been made.
E. A porous collagen/GAG scaffold, degrading with a half-life of 12 days, average pore diameter
100 μm, pore channels randomly oriented. No cells have been seeded into the scaffold prior to
grafting on the wound.

Solutions
A. This approach is expected to have no efficacy since epithelial cells by themselves are known
not to synthesize the stroma in skin wounds. Its safety can be high by making sure that the
autologous epithelial cells are extracted from the surgically removed conjunctival tissues that were
procured when the wound in the dysfunctional eye was surgically generated. However, the design
would have very low safety if it calls for extraction of cells from a biopsy of healthy conjunctival
tissue from the patient’s healthy eye (since it will threaten loss of normal vision in the remaining
healthy eye).
B. The synthetic polymer has no efficacy because it lacks ligands for binding integrins of
contractile fibroblasts. Even if there is nonspecific binding on the synthetic polymer surface, absent
specific ligands there is little expectation that contraction blocking (a requirement for regeneration)
will occur. The safety of the device is questionable: Even though it will eventually degrade in 2-3
weeks, the product of degradation of each of the comonomers is a pH-lowering substance (e.g.,
lactic acid) that should cause a local inflammatory response.
C. This system suffers from lack of specific ligands, as in section B above, and cannot block
contraction. Seeding with epithelial cells may possibly lead to synthesis of an epithelial tissues but

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the stroma will still be missing because it requires the presence of an active scaffold that can induce
changes in the phenotype of contractile fibroblasts.
D. Induced regeneration consists of two steps: wound contraction blocking and synthesis of new
stroma. The expected efficacy could be high since the substance will probably result in contraction
blocking, a prerequisite to regeneration. However, in the absence of a scaffold that can act as a
template for synthesis of new stroma, it is questionable whether new stroma will be synthesized at
all. The safety of the substance is unknown and it must therefore be assumed to be low and that it
requires testing for toxicity.
E. This scaffold is DRT, which is known to lead to regeneration of the stroma. Epithelial tissue
will not be specifically induced to regenerate by use of the unseeded scaffold. However, for a
small-area wound, as this 2 x 2 mm2 wound is, it is expected that epithelial tissue will migrate
from the wound edges toward the wound center, with synthesis of the epithelial tissue and
spontaneous synthesis of basement membrane. (This process works well with skin wounds that
have been grafted with a keratinocyre-seeded DRT.) Efficacy should be high. Since all three tissue
types will be synthesized. Safety should also be high since this scaffold has passed clinical trials
in its use as a device that regenerates skin and peripheral nerves.

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