Neoplasia, new growth, an

unregulated process of excessive

and uncontrolled cell
proliferation. The new growth is
called a neoplasm or tumor
1a

What is tumorigenesis?

1b

Proliferating neoplastic cells

that form the parenchyma
and supportive stroma made
of connective tissue and
blood vessels
2a

What two things do all

tumors consist of?
2b

A stimulus causing malignant

transformation via
mutagenesis
3a

What is a carcinogen?

3b

An accumulation of genetic
damage
4a

Malignant transformation is a
multistep process, a result of
______________
4b

False: tumors associated with

therapeutic clinical implants in
humans are rare and causality is
hard to demonstrate. < 50 cases
of tumors associated foreign
materials

5a

True or false: biomaterial

implantation poses a large
risk for tumorigenesis
5b

Physical

6a

______ effects may play a

more important role than
chemical effects in
tumorigenesis of
biomaterials
6b

Solid; continuous

7a

________ materials with

_______ surface area are most
tumorigenic
7b

Directly to the extent and

maturity of tissue
encapsulation and inversely
with the degree of active
cellular inflammation
8a

What does solid state

tumorigenesis correspond
to?
8b

1) Cellular foreign-body reaction

2) Fibrous capsule formation
3) Preneoplastic cells contact implant surface
during quiescent tissue reaction (dormancy
and phagocytic inactivity of macrophages)
4) Preneoplastic cell maturation and
proliferation
5) TUmor growth

9a

What is the 5 step hypothesis

on foreign-body
tumorigenesis?
9b

Small fiber tumorgenesis

10a

What is mesothelioma?

10b

1) Initiation: implantation of biomaterial

causes malignant transformation of DNA
due to chemical carcinogenesis or
foreign-body carcinogenesis
2) Latency: time period varies
3) Promotion: obvious tumor growth
around implant
11a

What are the 3 steps of

biomaterial tumorgenesis
11b

Data from other sources

suggest a tendency for tumor
induction (regulated by ISO
and ASTM)
12a

Carcinogenicity tests should

only be conducted if...?
12b

In vitro cell culture, look for

mutation, chromosomal
aberrations and/or DNA
damage and repair
13a

How do you look for

mutagenic potential?
13b

Undertaken as a part of general

biocompatibility testing, non-carcinogenic
control like PE required, animal model
and duration established, tissue excised
at various time points and evaluated
using histology and SEM to detect tumor
growth
14a

Name 4 characteristics of
long term animal bioassays
14b

Invasion by and multiplication of

pathogenic microogranisms in a
bodily part or tissue, which may
produce subsequent tissue injury and
progress to over disease through a
variety of cellular or toxic mechanisms
15a

What is infection?

15b

5-10%

16a

What percentage of patients

with implanted devices
develop infection?
16b

1) Presence of biomaterial and/or damaged underlying

ECM
2) Bacterial colonization of tissue
3) Resistance to host defense and antibiotics
4) Transformation of innocuous bacterial species into
virulent organisms
5) Presence of multiple bacteria species
6) Persistence of infection until removal
7) Absence of biomaterial-host integration
8) Presence of cell damages or necrosis
17a

Name 8 characteristics of
implant-associated infection
17b

Gram-positive bacteria such as

Staphylococcus aureus and
Staphylococcus epidermis, gram
negative bacteria such as
enterobacteriaceae and Pseudomonas
aeruginosa, and fungi such as
cabduda spp

18a

Name 3 common pathogens

associated with biomaterial
infection
18b

Immediate infection: introoperative contamination or

postoperative complications,
superficial or deep, often caused
by skin-dwelling
Late infection: blood-borne route

19a

What are the 2 categories of

infection associated with
biomaterials? Define them
19b

single or many bacteria as

well as fungi, algae, protozoa
, debris and corrosion
products
20a

What is a biofilm?

20b

When bacteria adhere to

surfaces in aqueous
environments and begin to
excrete a slimy, glue-like
substance that can anchor them
to all kinds of material surfaces

21a

When do biofilms form?

21b

All failed implanted medical

devices
22a

Biofilm has been found on

________.
22b

Bacterial attachment,
bacterial adhesion,
aggregation (biofilm
formation), dispersion
23a

What are the 4 steps of

infection?
23b

van der waals force first and

reversible
24a

What mediates bacterial

attachment? Is it reversible or
irreversible?
24b

ligand-receptor binding;
irreversible
25a

What mediates bacterial

adhesion? Reversible or
irreversible?
25b

Change phenotypes, produce matrix,

proliferate and further recruitment, form
microcolony, maintain structural integrity and
move independently, mature into a thick and
stable structure. Biofilm traps the ions needed
for survival, forms a physical barrier to
phagocytes, inhibits T and B cell formation and
function and imparts antibiotic resistance

26a

What mediates aggregation

and biofilm formation
26b

Leads to spreading of the

infection
27a

What is dispersion?

27b

Providing access to the circulation and

deeper tissue by damage to natural
barriers against infection, provides
surfaces for bacteria to attach, limits
phagocyte migration to infected tissue
or interferes with inflammatory cells
28a

How does implantation

facilitate infection?
28b

The number/types of cells in the liquid

to which the device is exposed, the
flow rate of liquid through the device,
the physicochemical characteristics of
the surface, components in the liquid
that may alter the surface properties
29a

The rate of microorganism

attachment to implanted
devices depends on what 4
things?
29b

Trapped in the slime

30a

Once microorganisms
irreversibly attach and produce
extracellular polysacchardies to
develop a biofilm, bacteria are
no longer directly attached to the
surface but...?

30b

Flow rate, nutrient

composition of the medium,
antimicrobial-drug
concentration, and
temperature
31a

The rate of biofilm growth is

influenced by what 4 things?
31b

False, surface modification

has not been successful
32a

True or false, surface

modification can help control
biofilm development
32b

DC field/ultrasonic energy,
potential agents, and delivery
of agents to kill planktonics
before they initiate the
biofilm
33a

What 3 things can help

biofilm control?
33b

Render sessile cells more

susceptible to antibiotics
34a

What does DC field and

ultrasonic energy do?
34b

Kill incoming planktonic cells,

and lock in their phenotype
(signal blockers)
35a

What do potential agents do?

35b

Generation of resistant
strains by sublethal dose
from exhasuted biomaterials
36a

What is one possible

problem with local release of
antibiotics from a surface?
36b

Moist heat, ethylene oxide,

radiation
37a

Name 3 sterilization methods

37b

Metallic and heat resistant

surgical instruments and
supplies
38a

What is moist heat good for

(sterilization wise)?
38b

Advantages: efficacy, speed,

simplicity and lack of toxic
residues. Disadvantages: high
temp and pressure degrade the
product and packaging materials
39a

What are the advantages and

disadvantages of moist heat
as a sterilization method?
39b

Advantages: efficacy, high

penetration ability, compatibility
with many materials.
Disadvantages: residues with
respect to both the implant and
environment

40a

What are the advantages and

disadvantages of ethylene
oxide as a sterilization
method?
40b

Advantages: simple, rapid,

and effective. Disadvantages:
high cost and incompatibility
in some materials (PTFE)
41a

What are the

advantages/disadvantages of
radiation as a sterilization
method?
41b

To determine if a biomaterial
encourages or discourages
bacteria attachment or to
analyze the source of
infection
42a

What can in vitro models be

used for to study infection?
42b

For blood contacting devices

43a

What can ex vivo shunt

models be used for to study
infection?
43b

to study markers of infection:

leukocyte and lymphocyte
counts, amount of bacterial cell
wall antibodies found in the
blood, presence of LPS
44a

What can in vivo models be

used for to study infection?
44b

Formation of nodular
deposits of calcium
phosphate or other calcium
containing compounds
45a

What is calcification?

45b

Desired for oseoinductive materials

used for orthopedic and dental
applications. Undesired for non
skeletal tissue replacement and
devices that are not supposed to
calcify (resulting in mechanical failure)
46a

When is calcification
desired/undesired?
46b

Dead cells and cell

membrane fragments
47a

What are the principle sites

of pathologic calcification?
47b

Polymeric bladders/heart valves in

blood pumps, breast implants,
intrauterine contraceptive devices,
urinary stents and prostheses, soft
contact lenses, tissue heart valve and
vascular graft
48a

Give 6 examples of
biomaterial calcification
48b

Porcine aortic valve or bovine

pericardium fixed with
glutaraldehyde to preserve
tissue, kill cells and reduce
immunogenicity
49a

What is a xenograft heart

valve?
49b

Human cadaveric aortic or

pulmonary valves with or without
vascular conduits; exceptionally
good hemodynamic profiles, low
thromboembolic complications,
low infections, cryopreserved
50a

What is an allograft heart

valve?
50b

Pseudoanatomic central flow

51a

What type of flow has a low

rate of thrombosis?
51b

Structure failure due to

progressive tissue
deterioration like calcification
and non-calcific damage
52a

How do heart valves fail?

52b

Tear and stiffening (stenosis)

53a

What is cuspal calcifcation?

53b

On cusps

54a

What is intrinsic calcification?

54b

In thrombi or endocarditic
vegetations
55a

What is extrinsic calcification?

55b

Phosphate containing proteins on the cell

membranes act as nucleation site; alkaline
phosphatase on the membrane promote
calcification; nonviable cells lost the mechanism
to transport away the Ca2+; fixing agents such
as gluteraldehyde stabilize the cell surface
proteins; mechanical force results in cell death
which results in calcification; collagen acts as a
template for the growth of mineral crystals

56a

What are 6 causes of

calcification?
56b

Systemic treatment or local delivery of

anti-calcification agent; biomaterial
modifications like removing the calcifable
component, adding exogenous agent,
chemical alteration; modification of
glutaraldehyde fixation or other crosslinking agents; alternative materials and
tissue engineered materials

57a

What are 4 ways to prevent

calcification?
57b

Remove phosphate
containing proteins and
acidic phospholipids
58a

How can surfactants prevent

calcification?
58b

Extracts lipids, permanently

alters collagen conformation,
affects cuspal interactions with
water and lipids, enhances
cuspal resistance to collagenase
59a

How can ethanol prevent

calcification?
59b

Physiologically relevant
media with chemical
composition mimiking urine
or blood CSF etc
60a

How can you assess

calcification?
60b

Subcutaneously or in final
location; section/stain for Ca
content, analyze explant using
SEM, SEM-EDAX, X-ray
diffraction, or using in situ
imaging

61a

How can you asses

calcification in vivo?
61b