Presence of macrophages,

monocytes, and lymphocytes

with proliferation of blood
vessels and connective tissue
1a

What is the definition of

chronic inflammation?
1b

Release products that mediate

the response, antigen
presenters, part of the
reticuloendothelial system
responsible for systemic effects
2a

What 3 functions do
macrophages have?
2b

neutral proteases, chemotactic

factors, reactive oxygen
metabolites, complement
components, coagulation
factors, growth factors, cytokines
3a

What do macrophages
release? (7 things)
3b

Key mediators of acquired

immunity; Their role in nonimmunologic injuries and
inflammation is not very clear.
Th2 helper cells release IL-4
4a

What are lymphocytes

and what is their role?
4b

Short-lived; granulation;
persistent
5a

__________ chronic
inflammatory response
followed by ________ is
normal, while _______
inflammation is pathologic.
5b

Physical, chemical,
motion, infection
6a

Persistent inflammatory
stimuli lead to chronic
inflammation...what are
the 4 types?
6b

One day after

implantation and can be
seen 3-5 days following
implantation
7a

When does granulation

tissue initiate?
7b

Fibroblasts and vascular

endothelial cells proliferate and
begin to form granule tissue,
pink soft granular appearance
on the surface of healing wounds
8a

What is granulation
tissue?
8b

Formation of small blood

vessels through budding
or sprouting from
existing ones
9a

What is angiogenesis?

9b

Synthesize collagen and

proteoglycans
10a

What do fibroblasts do?

10b

Foreign body giant cells and

components of granulation
tissue like macrophages,
fibroblasts, capillaries
11a

What is a foreign body

reaction composed of?
11b

Multi-nucleated cells formed by

the fusion of
monocytes/macrophage in an
attempt to phagocytose foreign
materials that are much larger
than a single cell

12a

What are foreign body

giant cells?
12b

form and topography

13a

The _______ and _______ of

the surface determine
the composition of the
FBR
13b

A layer of macrophages
and fibrosis
14a

Flat and smooth surfaces

result in what kind of
FBR?
14b

Mixture of macrophages
and foreign body giant
cells
15a

Rough surfaces result in

what kind of FBR?
15b

Particulate and microspheres

will have higher ratios of
macrophages and foreignbody giant cells to fibrous
(granulation) tissue
16a

In high surface to volume

ratio implants, what kind
of foreign-body reaction
results?
16b

End stage healing response,

granulation tissue maturation,
larger blood vessels and
alignment of collagen fibers in
response to local mechanical
forces

17a

What is fibrosis?

17b

Degree of initial implantation

injury, amount of subsequent
cell death, location of implant
site, microstructure of implant
(porosity), degradation time of
implant (if degradable)

18a

The degree of fibrous

capsule formation
depends on what 5
things?
18b

Amount/composition of small
particulates produced,
mechanical factors at the implant
site, shape of implant, electrical
currents (if produced)
19a

The thickness of a
capsule may be affected
by what 4 things?
19b

regeneration and
replacement
20a

There is a balance
between _______ and
__________ by connective
tissues
20b

Regenerative capability of cells,

persistence of the underlying
framework/supporting stroma,
extent of injury, site of injury,
species
21a

What 5 things control

injury repair?
21b

Labile, stable, permanent

22a

What are the 3

regenerative capacities
cells can assume?
22b

significant infection; loss

of tissue
23a

Small wounds result in

no _______ with minimal
_______
23b

regeneration of
parenchyma cells;
granulation tissues
24a

With larger wounds, there is

not enough _________ of
______ cells, a larger amount
of _________, and large
fibrosis
24b

Site of implantation,
adequacy of blood
supply, potential for
infection
25a

What are 3 local factors

in the wound healing
response?
25b

Nutriton, hematologic
derangements, glucocortical
steroids, preexisting diseases
like atherosclerosis, diabetes,
and infection
26a

What are 4 systemic

factors in the wound
healing response?
26b

Extrusion, resorption,
integration, or
encapsulation
27a

What are the 4 types of

resolution to implants?
27b

Epithelial tissue

28a

What is extrusion?

28b

Resorbable material, no
fibrous capsule formation or
capsule collapse or replaced
by the host tissue
29a

What is resorption?

29b

No intervening fibrous
capsule
30a

What is integration?

30b

Traditional response to
non-resorbable materials
31a

What is encapsulation?

31b

causes toxic effects at the

cellular level such as death,
alterations in membrane
permeability, enzymatic
inhibition, etc.
32a

What is cytotoxicity?

32b

low molecular weight

organotin stabilized PVC,
gum rubber, dilute solutions
of toxic chemicals
33a

What positive controls

can be used in
cytotoxicity assays?
33b

high density
polyethylene
34a

What negative control

can be used in
cytotoxicity assays?
34b

Direct contact, agar

diffusion, and
elution/extract dilution
35a

What are 3 morphological

cytotoxicity assays?
35b

Place the test sample directly in the

culture. Observe under the
microscope, live/dead stain, MTT
assay, etc. Advantage is that it mimics
clinical use. Disadvantages include
risk of physical trauma, influenced by
the diffusion rate of the leachables

36a

What is meant by a direct

contact assay? What are the
advantages/disadvantages?
36b

In an agar diffusion flask containing a

sample of positive control material, the
discoloration that extends outward from
the material indicates that the presence
of the sample has caused the cells to lyse,
losing the vital stain incorporated in the
agar layer
37a

What is an agar diffusion

test?
37b

Advantages are the better concentration

gradient and you can test one side of a
material. The disadvantages are that it
requires a flat surface and it is limited by
the solubility of toxicant in agar, risk of
thermal shock, risk of absorbing water
from agar
38a

What are the advantages

of an agar diffusion test?
Disadvantages?
38b

Determines the cytotoxicity

of leachables. Soak test
material in MEM and apply
the extract mediat different
dose to the culture
39a

What does an elution test

determine? How does it
work?
39b

Advantages: separate the

extraction from testing, can test
dose response, have choice on
extract conditions,
disadvantages: additional time
and steps

40a

What are the

advantages/disadvantages
of an elution test?
40b

Grainy cells that lack normal

cytoplasmic space;
considerable open areas
between cells indicate that
extensive lysis has occurred
41a

What do cells that have a

cytotoxic reaction look
like?
41b

A well defined confluent

layer of cells exhibiting
cell to cell contact
42a

What do cells that have a

noncytotoxic reaction
look like?
42b

1) Species must be similar in

physiology/healing response to human,
start with a small animal and then move
to larger 2) Implant site should be close to
application site, but you can start
somewhere more accessible 3) Length of
study for multiple time points
43a

What are 3
considerations in the
development of an
animal model?
43b

1) Extracts, material or device

2) Implant weight or bulk size
3) Surface area
4) Topography
5) Number of implants per
animal

44a

What 5 biomaterial
considerations are
included in in vivo assay
design?
44b

Histology/immunohistochemistry,
electron microscopy, and
biochemical assays
45a

What are 3 methods of in

vivo assay assessment?
45b

1) Fix the tissue with fixatives

2) Sectioning
3) Staining with conventional
dyes or antibodies
4) Imaging
5) Quantification

46a

What 5 steps are involved in

histology/immunohistochemistry

46b