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Bioengineering
Flashcards for Biomaterials
235
Engineering
Undergraduate 2
12/07/2011

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Term
Gibbs free energy
Definition
ΔG = ΔH −TΔS (chemical reactions are spontaneous when
ΔG < 0 )
Term
enthalpy
Definition
H, a measure of the amount of energy in a
system available for mechanical work
Term
entropy
Definition
S, a measure of the disorder of the system
Term
three factors on protein adsorption
Definition
Dehydration, redistribution of charged groups, structural
rearrangement
Term
number of amino acids
Definition
20
Term
proteins
Definition
Since the bonds between amino acids are called peptide bonds,
are a kind of polymers. proteins are also called polypeptides. Polypeptides are formed
via condensation reactions
Term
primary structure
Definition
linear order of amino acids as dictated by
the codons. has a fundamental influence
in all other levels of structures. Example, substitution of a single amino acid in the polypeptide chain that composes
hemoglobin, the protein that carries oxygen in the blood,
changes its overall folded shape and results in the disease
known as sickle cell anemia
Term
secondary structure
Definition
caused by localized interactions between
amino acid residues. α -helix structure is one of the two most common types of
secondary structures. β -pleated sheet structure is another one of the two most
common types of secondary structures
Term
tertiary structure
Definition
three-dimensional arrangement of an
entire polypeptide chain It shows the secondary structural
elements are folded. A common example is triosephosphate
isomerase (TIM)-barrel fold (this distinctive structure has eight
parallel β -strands surrounded by eight α -helices on the
outside)
Term
quaternary structure
Definition
describes the three-dimensional
arrangement of the polypeptide chains. If there are one, two,
three, and more chains, it is monomer, dimmer, trimer, etc,
respectively When pH changes, protein structures are changed, which
subsequently changes the adsorption of proteins on the surface
of a biomaterial.
Term
Transport of proteins to surface is affected by
Definition
diffusion, thermal convection, flow (also called
convective transport), coupled transport (combinations
of others, such as convection and diffusion). Transport phenomena due to flow, thermal convection, and
diffusion
Term
The velocity profile
Definition
given by V = 2Q/(μR^2)*[1-(r/R)^2], where V is the
velocity, Q is the volumetric flow rate of liquid through the cylinder, μ is the viscosity, and r and R are radial distance and
the radius of vessel, respectively
Term
The protein transport equation
Definition
given by ∂C/∂t + V*∂C/∂z = D*1/r*∂/∂r*(r ∂C/∂r), where C stands for the concentration of a protein at time t ,
position z (axial), and r in a vessel, V is the velocity, D is
diffusion coefficient (this equation only describes the transport
of the protein through a solution, but not the rate of transport of
protein to the surface)
Term
Monolayer protein coverage
Definition
Rearrangement of proteins on a surface to allow more proteins
to be adsorbed to the surface, which explains why the rate
adsorption increase after a slow down
Term
reversible binding
Definition
Proteins may first be adsorbed to the surface loosely
Term
irreversible binding
Definition
then change their conformation to bind to
the surface permanently
Term
Vroman effect
Definition
a phenomenon where proteins with higher
concentration will rapidly attach, and then be replaced over
time by proteins with greater surface affinity
Term
Desorption and exchange
Definition
Initially adsorbed proteins may be exchanged by other proteins
with a stronger affinity to the surface
Term
Adsorption chromatography
Definition
is one type of affinity
chromatography. It measures the time that proteins stick to a
particular chemical analyte (column) in the instrument to
determine the types of proteins contained in the sample
injected. Proteins that stick strongly to the column will come
out later
Term
types of adsorption chromatography
Definition
normal
phase chromatography (more hydrophilic molecules are euted
later); and (2) reverse-phase chromatography (more hydrophilic
species are eluted first)
Term
Ion exchange chromatography
Definition
another type of adsorption
chromatography, but its discussion is beyond the scope of the
text.
Term
Colorimetric assays
Definition
are the simplest test for the presence of a
given protein involves direct reaction of the component with a
marker chemical to cause a specific color change (the molecule
causing this specific color is called chromophore)
Term
Fluorescent assays
Definition
are similar to the colorimetric assays but
here the reaction causes the attachment of a fluorescing
molecule (fluorophore) to the protein of interest. After the attachment of fluorophore in the protein smaple,
visible light of specific wavelengths is used to excite the
molecules in the sample and the fluoresced lights are detected. are able to quantify fluorescently labeled
protein molecules
Term
A fluorometer
Definition
an instrument that uses fluorescence to
identify proteins
Term
advantages of fluorescent assays
Definition
the
fluorescent phenomena are detectable at one to three orders of
magnitude lower concentration than that observable with
traditional colorimetric (absorbance) techniques; and if the
protein of interest contains enough of amino acids that are
intrinsic fluorophores, an additional reaction to label the protein
is unnecessary.
Term
enzyme-linked immunosorbent assay (ELISA)
Definition
used to
determine in the sample the amount of proteins that are specific
to a given antibody.
Term
A sandwich ELISA
Definition
which uses an antibody to identify proteins
and measure their amount through a spectrophotometer
Term
Western blot assay
Definition
used to determine the protein types
(different sizes) in the initial sample
Term
Sodium dodecyl sulfate (SDS)
Definition
used to treat the sample first
before the western blotting process so that the proteins are
strongly negatively charged and can be attracted to the positive
electrode
Term
reversed-phase
chromatography
Definition
Areas of curves of reversed-phase HPLC chromatographs can
be used to determine the amount of certain separated species
present in the original sample
Term
There are two stimuli for activation of platelets
Definition
exposure to
soluble factors, and interaction with extracelluar matrix
(ECM) and/or cells of injured vessel walls
Term
Platelets are
Definition
nonnucleated fragments of megakaryocytes with a
diameter of 3-4 μm and a half-life of 8-12 days
Term
Two main hemostatic functions of platelets are
Definition
initially
reduce bleeding through the creation of a platelet plug, and further stabilize this plug through activation of the blood
coagulation cascade
Term
collagen and von Willebrand factor (vWF)
Definition
arepotent platelet activators
Term
The sequelae of activation of platelets are
Definition
change their
shapes from disc-like to irregular form, and release of stored
granule contents due to a contraction of cytoskeletal proteins in
the platelets.
Term
The function changes of activated platelets are
Definition
adhere to
ECM proteins, aggregate, secrete various bioactive
factors for further platelet stimulation, and exhibit
coagulatory activity (promote localized blood coagulation).
Term
Intrinsic and extrinsic pathways
Definition
Both pathways result in a
common pathway that converts fibrinogen to fibrin, the main
constituent of the blood clot.
Term
Calcium chelators
Definition
are substances that bind calcium and are very
effective anticoagulants (calcium is needed to form
coagulation).
Term
Intrinsic pathway
Definition
is initiated by trauma to blood itself or
exposure of blood to exposed extracellular matrix (ECM)
molecules in a damaged vessel wall. It begins with adsorption
of one of the coagulation contact proteins, Factor XII, to a
negatively charged surface
Term
Extrinsic pathway
Definition
is initiated by the release of tissue factor
(TF) and clotting can commence via this pathway within 15
seconds.
Term
Common pathway
Definition
depends on the activations of stimulated
platelets.
Term
Thrombin
Definition
an enzyme that is extremely important substance
in the coagulation cascade, with both pro- and anticoagulant
activities. It cleaves fibrinogen to form fibrin monomer and
fibrinopeptides that can be polymerized to form long fibrin
fibers for blood clotting. Thrombin is synthesized and released
by platelet. It catalyzes the production of more thrombin and
stimulates adenosine diphosphate (ADP) and thromboxane A2
release.
Term
Two means of coagulation control
Definition
physiological factors
(such as normal blood flow), and soluble and insoluble
biochemical factors (soluble agents may bind coagulation
factors and inhibit their actions and insoluble substances such
as thrombomodulin that is found on the endothelial surface of
the blood vessel walls plays a large role in the control of
coagulation)
Term
Clot dissolution
Definition
is required to restore normal blood flow to the
damaged area. It occurs primarily via fibrinolysis, or cleavage
of the fibrin fibers in a controlled manner
Term
Endothelium
Definition
the interior wall of a blood vessel. It has a
number of anticoagulative properties in its native state but it
will be a main mechanism of coagulation initiation after injury
where the protective glycocalyx is compromised
Term
Glycocalyx
Definition
a coating of endothelium and imparts smoothness
to the walls of the vessel
Term
Five categories of hemocompatibility that need to be tested
Definition
thrombosis, coagulation, platelets, hematology, and
immunology (complement and leukocyte activation)
Term
Local and systemic effects
Definition
local effects are localized blood
clotting that could negatively affect device function, and systemic effects of device-mediated coagulation include
thrombus embolization, in which pieces of the clot break off
and are carried elsewhere in the circulatory system.
Term
Both local and systemic effects from blood contacting devices
can result from the following three factors
Definition
blood characteristics, flow regime, and material surface
characteristics.
Term
There are four quantifiable parameters for in vitro test of
hemocompatibility
Definition
coagulation time, amount of adhered
platelets, mass of adherent thrombus, amount of platelet
granule released (this requires specific assays for chemical
mediators found in platelet granules, such as platelet factor-4
and β –thromboglobulin)
Term
In vitro hemocompatibility tests
Definition
have a low cost but have a
limited value for prediction of in vivo responses
Term
Factors to consider for in vivo hemocompatibility tests include
Definition
choice of animal, length of study and choice of time
points, and inclusion of proper control materials.
Term
Ex vivo hemocompatibility tests
Definition
are in vivo tests but they place
devices being tested outside of body and use tubes to connect
them with blood vessels in the body.
Term
Innate immunity
Definition
a nonspecific immunity that is the first line
of defense.
Term
Acquired immunity
Definition
a specific immune response that involves
the activation of a type of white blood cell called lymphocyte
Term
Infection develops
Definition
if the organism persists after exposure to
both the innate and acquired immune response.
Term
Leukocytes
Definition
are white blood cells
Term
There are several types of leukocytes
Definition
granulocytes (can be subdivided into neutrophils, eosinophils
and basophils), monocytes (have a large phagocytic
capability), lymphocytes/plasma cells (part of the acquired
immune response), and megakaryocytes (in the bone
marrow to produce platelets).
Term
Leukocytes are produced
Definition
from the pluripotent hematopoetic
stem cell.
Term
Leukocytes are only present
Definition
in the blood to be transported to a
tissue where they are needed.
Term
There are four main components of the defense provided by
innate immunity
Definition
anatomic barriers (skin and mucous
membranes), physiologic barriers (temperature of body, low
pH or acidic in stomach),phagocytic cells (granulocytes),
and inflammation (tissue swelling when one gets injured).
Term
There are four clinical signs of inflammation
Definition
rubor
(redness), tumor (swelling),tumor (swelling), dolore (pain).
Term
Acute inflammation
Definition
a part of innate immunity and is an
immediate response to tissue injury.
Term
chronic inflammation
Definition
a symptom persists over
weeks to months
Term
Extravasation
Definition
a movement of the neutrophils out of the blood
vessels and into the tissue
Term
There are four steps of migration of neutrophils
Definition
rolling, activation, arrest and adhesion, and migration.
Term
A main task of neutrophils
Definition
to phagocytose foreign agents.
This process is called phagocytosis
Term
Respiratory burst
Definition
a glucose metabolism that is increased up
to tenfold and oxygen consumption increased two- to threefold,
which leads to the formation of reactive oxygen and nitrogen
species (radicals and strong oxidizers) in intracellular granules
and then released to kill foreign organisms
Term
Cytokines
Definition
are secreted by neutrophils to have specific effects
on several cell types, such as, attract lymphocytes and attract
more neutrophils
Term
Monocytes arrive
Definition
at the injury site five to six hours after the
inflammatory response begins (partially due to the signals
released by the neutrophils).
Term
Macrophages are
Definition
enlarged monocytes. They mature in up to
eight hours and involve swelling of the cell and formation of a
large quantity of lysosomes
Term
Phagocytosis proceeds
Definition
in the same way as for neutrophils but
an individual macrophage can engulf many more bacteria or
particles than a neutrophil.
Term
Frustrated phagocytosis
Definition
is observed if the size of the
nondegradable material is much larger than that of the cell
Term
Chemical mediators
Definition
are secreted by activated macrophages
Term
Effects of some or all of the chemical mediators are
Definition
effects
on the inflammatory response, effects on the acquired
immune response, and systemic effects
Term
antigen-presenting cell (APC)
Definition
is a key function of
the macrophage (provides a direct connection between the
innate and acquired immune responses)
Term
Other granulocytes
Definition
eosinophils (have a smaller phagocytic
capacities as compared to neutrophils/macrophages, but they
are important because they destroy parasites and detoxify some
of the inflammation-inducing agents), and basophils
(similar to mast cells that release heparin, histamine, bradykinin
and serotonin, which are soluble mediators of inflammation)
Term
Acute inflammation is terminated
Definition
as the stimulus for acute
inflammation is removed
Term
Indicators of activation of leukocyte (that are most commonly
neutrophils or macrophages) due to biomaterials are
Definition
cell
adhesion and spreading, cell death, cell migration, cytokine release, and cell surface marker expression.
Term
Leukocyte assays
Definition
generally examine one or more indicators of
activation of leukocyte.
Term
Cell characterization via fluorescence-activated cell sorting
(FACS)
Definition
is based on immunostaining techniques (see
Chapter 9) for tagging antibody to the receptor of interest on
the inflammatory cells
Term
Test of response of endothelial cells
Definition
is a further in vitro assay
for the inflammatory potential of biomaterials
Term
The upregulation of cell surface receptors or ligands on
endothelial cells
Definition
promotes the migration of neutrophils and
macrophages and thus is a key step in the inflammatory
response.
Term
three major stages for wound healing
Definition
acute
inflammation, chronic inflammation, and granulation
tissue formation
Term
Granulation tissue
Definition
a tissue characterized histologically by a
pebbly, granular appearance (thus its name)
Term
Neovascularization or angiogenesis
Definition
the process of production
of granulation tissue that is formed by the creation of many
vascular buds sprouting from existing blood vessels.
Term
Myofibroblasts
Definition
are some of the fibroblasts that take on features
of smooth muscle cells. They are responsible for wound
contraction, which results in faster healing due to a decrease in
the overall defect size
Term
The foreign body reaction is dependent on several factors
associated with the implant
Definition
surface properties of the
material (smooth surfaces invoke only macrophages that are
only one to two cells in thickness, while rough surfaces may
have a mixture of macrophages and FBGCs); and the shape
of the implanted material (in particular, a high surface area to
volume ratio will have higher ratios of macrophages and
FBGCs at the tissue-material interface, while implants with a
lower surface area to volume ratio show more fibrous or
granulation tissue production)
Term
Foreign body reaction
Definition
a process that involves foreign body
giant cells (FBGCs) and the elements of granulation tissue
Term
Fibrous encapsulation
Definition
the final stage of healing for implants
made from nondegradable materials
Term
There are four factors on degree of long-term capsule
formation
Definition
degree of original injury during implantation, amount of subsequent cell death, location of implant site,
and degradation time of implant (if degradable)
Term
four factors on thickness of the capsule
Definition
amount and composition of small particulates produced, mechanical factors at implant site, shape of implant, and electrical currents (if produced).
Term
Size of the fibrous capsule
Definition
increases in proportion to the rate of
shedding of small particulates, which can be caused by
corrosion, degradation, and wear
Term
Thicker capsules
Definition
may correspond to current density of
electrodes.
Term
Chronic inflammation
Definition
characterized by the presence of
mononuclear cells, including lymphocytes and plasma cells,
which may also indicate that the material has triggered an
acquired immune response. It is also less uniform histologically
than acute inflammation.
Term
Resolution
Definition
to restore to the body’s status quo after injury
through inflammation and wound healing response
Term
There are four main types of possible resolutions
Definition
extrusion
(force materials out of body), resorption (implant is
biodegradable), integration (in limited cases such as
implantation of pure titanium in bone), and encapsulation
(traditional response to nonresorbable materials).
Term
The two processes to form functional tissues are
Definition
repair (for
deeper wounds); and regeneration (for small wounds).
Term
Dermal layer
Definition
internal
Term
epidermal
Definition
outer layer
Term
Skin regeneration
Definition
a reepithelialization (for smaller skin
wounds that are contained in the epidermal layer and a full
regeneration of the defect are possible).
Term
Factors that are related to a biomedical implant that may affect
the in vivo response
Definition
the material(s); intended additives,
process contaminants, and residues; leachable substances; degradation products; other components and their
interactions in the final produce; and the properties and
characteristics of the final product.
Term
There are four means of in vivo biological responses for the
factors that are related to the biomedical implant
Definition
interactions of biological molecules or cells with the implant, interactions of biological molecules or cells with soluble
agents leached from the implant, interactions of biological
molecules or cells with insoluble particulates, and alterations in load or strain in the area around the implant (can
be caused by material properties, but is also affected by
geometry and final properties of the device).
Term
Biocompatibility
Definition
the ability of a medical device to perform
with an appropriate host response in a specific application
Term
Biocompatibility assessment
Definition
to measure the magnitude and
duration of the adverse alterations in homeostatic mechanisms
(includes carcinogenicity, hemocompatibility, immune
response, and the inflammatory response).
Term
proper selection of animal species is based upon
Definition
on a similarity in
physiology and healing response to that which would occur in
humans for a given application.
Term
Implant site in an animal
Definition
should be the site that is as close as
possible to that which will be used in the final application
Term
There are four different lengths of study
Definition
acute toxicity (up
to 24 hours), subacute toxicity (14-28 days), subchronic
toxicity (within the first 90 days or less than 10% of the
lifetime of the animal), and chronic toxicity (longer time).
Term
There are four factors of “Dose”
Definition
implant weight and/or
bulk size, implant surface area, implant topography, and number of implants per animal.
Term
“Dose”
Definition
means effects of the shape of the implant material.
Term
In histology/immunohistochemistry
Definition
tissues containing the
implant are sectioned and stained, either with conventional dyes
or antibodies, after explantation.
Term
two forms of microscopy that can be used to examine tissue response to an implant
Definition
transmission electron microscopy (TEM) and scanning
electron microscopy (SEM)
Term
Biochemical assays
Definition
help assess inflammation after
biomaterial implantation.
Term
Mechanical testing
Definition
used to test explanted specimens
including the implant and surrounding tissue on a mechanical
testing frame.
Term
Three additional effects of biomaterials are
Definition
infection, tumorigenesis, and pathologic calcification.
Term
There are nine characteristics of implant-associated infections
Definition
presence of biomaterial and/or damaged underlying
extracellular matrix (ECM), bacterial colonization of tissue, resistance to host defense mechanisms and antibiotic
therapy, presence of characteristic bacteria types, transformation of relatively innocuous bacterial species into
virulent organisms by the presence of a biomaterial, presence of multiple bacteria species, persistence of
infection until removal of the substratum, absence of
integration of the biomaterial with the host, and presence of
cell damage or necrosis.
Term
Three organisms that are most often responsible for
biomaterial-related infection
Definition
gram-positive bacteria
(staphylococcus aureus and staphylococcus epidermidis), gram-negative bacteria (Enterobacteriaceae and pseudomonas
aeriginosa), and fungi (candida spp).
Term
Superficial immediate infection
Definition
occurs if there is growth of
microorganisms on the skin in association with an implant (e.g.
growth under burn dressings)
Term
Deep immediate infection
Definition
occurs at the implant site soon after
surgery
Term
Late infection
Definition
may occur months to years after the implantation
surgery
Term
There are four stages of a clinical infection
Definition
bacterial
attachment (to the surface of biomaterial), adhesion
(binding with receptor-ligand interactions), aggregation
(divide and form colonies, exude an extracellular
polysaccharide slime to form biofilm, which may occur as early
as one day after bacterial attachment), and dispersion
(carrying a portion of the bacterial colony to other areas of the
body, which may occur as soon as two days after initial
bacterial attachment).
Term
Biofilm
Definition
a film that protects the microorganisms from
phagocytosis by neutrophils or tissue macrophages and
provides a favorable environment for bacterial growth
Term
An ideal biomaterial surface would have two simultaneously
characteristics
Definition
bacteria resistant; and cell friendly; both
of which are directly related to the type of proteins that adsorb
to the material.
Term
Gram-positive bacteria species
Definition
have a single bilayered
phospholipids membrane and a thick cell wall composed of
peptidoglycan.
Term
Gram-negative bacteria species possess two phospholipids
membranes
Definition
the cell membrane; and an outer membrane
with a thin peptidoglycan cell wall between the membranes.
Term
Cell capsule
Definition
Certain species of both gram-positive and gramnegative
bacteria have such an outer layer composed of
polysaccharides that form the cell capsule.
Term
Biofilm coating
Definition
is an exudation of slime that forms a
specialized microenvironment (a microzone) that allows the
bacterial to trap ions important to their survival and protects
them from the body’s natural defenses (several types of bacteria
can be housed under a single biofilm coating).
Term
bacteria with biofilm
Definition
a 100 times greater concentration of oral antibiotics is needed to kill them
Term
Two important biomaterial surface properties that affect the
adhesion of bacteria are
Definition
surface hydrophobicity and charge.
Term
The two physical properties on bacteria adhesion are
Definition
steric
concerns; and surface roughness
Term
Media properties
Definition
have effects on the adhesion of bacteria. For
example, the type of proteins found in the media (solvent)
surrounding the material will affect bacteria adhesion.
Term
Nonspecific interaction involved in bacterial adhesion
Definition
is
modeled based on the work from Derjaguin, Landau, Verway,
and Overbeek (DLVO) theory. In the case of specific interaction, receptors and ligands can
extend into the media to promote binding and overcome the
energy barrier depicted in the DLVO model. Microbial surface components recognizing adhesive matrix
molecules (MSCRAMMs) are receptors of many bacteria for a
variety of ECM components
Term
Implant-associated infections
Definition
are unique in that they are usually
caused by transformation of relatively innocuous bacterial
species into virulent organisms by the presence of a biomaterial
(implanted biomaterial plays a compounding role in infection).
Term
Bacterial hydrophobicity
Definition
can be quantified using contact angle
measurements.
Term
Microbial adherence to hydrocarbons (MATH)
Definition
is another
technique to assess bacterial hydrophobicity
Term
Hydrophobic interaction chromatography (HIC)
Definition
is a more
quantitative assessment of the degree of bacterial
hydrophobicity.
Term
Electrophoretic mobility test
Definition
used for testing the surface
charge of bacteria surface.
Term
Electrostatic interaction chromatography (EIC)
Definition
an alternative
method to quantify the bacterial surface charge
Term
In vitro infection testing
Definition
focuses on quantification of bacterial
adhesion to biomaterials under static or well-defined flow
conditions.
Term
Ex vivo models of infection
Definition
involve the use of external shunts
connected to vessels, much like those described for
hemocompatibility testing.
Term
In vivo models of infection
Definition
use both small animals (rodents)
and larger animals.
Term
Tumorigenesis
Definition
formation of tumors
Term
Neoplasia
Definition
an excessive and uncontrolled cell proliferation
Term
Neoplasm
Definition
a tumor that is composed of proliferating
neoplastic cells and surrounding connective tissue and blood
vessels
Term
Benign tumors
Definition
tumors that do not invade adjacent tissues or
spread to distant sites.
Term
Malignant tumors
Definition
tumors that invade surrounding tissues
and gain entry into lymph and blood vessels, so they can be
transported to distant sites (this is called tumor metastasis).
Term
Carcinogen
Definition
a stimulus that causes malignant transformation
that is thought to occur due to mutations in the DNA of normal
cells (mutagenesis).
Term
Procarcinogen
Definition
not a carcinogen in its native form, but can be
converted to one by metabolic processes found in vivo
Term
Cocarcinogen
Definition
possesses little or no inherent mutagenic
potential, but enhances the activity of pro- or complete
carcinogens.
Term
three stages of tumorigenesis
Definition
initiation, latency (may be on the order of 15-20 years), and promotion.
Term
Chemical carcinogenesis
Definition
is tumor-causing substances that have
leached from the implant (hydrocarbon-based molecules are
usually carcinogens)
Term
Foreign body carcinogenesis
Definition
caused by solid implants with
even no chemical carcinogenic activity (the ability of the
material to induce malignant transformation increases with the
size of the implant).
Term
There are six possible causes of foreign-body carcinogenesis of
large implants
Definition
bulk chemical properties, physicochemical surface properties, viral contamination, interruption of cellular communication (due to the presence of
the implant), local tissue damage (leading to insufficient
nutrient exchange), and disturbed cellular growth (around
the implant).
Term
Small fiber tumorigenesis
Definition
Certain cancers have been
implicated by small fibers (less than 1 μm in diameter and more
than 8 μm in length), regardless of their chemical composition
(discovered in humans who have inhaled asbestos fibers and developed a type of cancer known as
mesothelioma).
Term
implant-related tumorigenesis
Definition
is relatively low for humans
Term
In vitro assays
Definition
used to test for mutagenic potential (all
carcinogens are mutagens).
Term
Ames test
Definition
a commonly used method of predicting mutagenic
potential (a mutant bacteria line that requires the amino acid
histidine for growth and thus only non-histidine-dependent
phenotype will be able to survive and proliferate in histidinefree
media if the biomaterial causes the bacteria to mutate).
Term
In vivo carcinogenesis assessment
Definition
generally undertaken as a
part of general biocompatibility testing, as suggested by ISO
and ASTM guidelines
Term
Pathologic calcification
Definition
an undesired formation of nodules of
calcium phosphate within or on the surface of an implanted
material (on devices such as cardiac valves, blood pumps,
urinary prostheses, and soft contact lenses).
Term
Mineralization
Definition
denotes the deposition of inorganic material in a
tissue.
Term
Calcification
Definition
denotes a subset of mineralization in which
calcium is the major specific inorganic material deposited in the
tissue
Term
Initiation of calcium deposits
Definition
thought that the calcium
deposits are initiated on dead cells or cell membrane fragments
(on proteins with attached phosphate groups that may act as nucleation sites to form calcium phosphate crystals) of
pretreated natural materials (pretreated with gluteraldehyde or
formaldehyde).
Term
There are three factors of pathologic calcification
Definition
host
metabolism, surface and bulk properties of the biomaterial
chosen, and the mechanical environment of the device.
Term
One way to reduce the occurrence of pathologic calcification
Definition
target calcium phosphate crystal initiation (including
localized release of inhibitors of calcium-phosphate crystal
formation such as trivalent metal ions, Fe3+ or Al3+).
Term
In vitro studies of calcium deposition
Definition
can be performed with
materials or entire devices placed in a bath containing media
approximating the chemical composition of a particular in vivo
location (e.g., urine or blood).
Term
There are two types of in vivo experiments for pathologic
calcification
Definition
subcutaneous implantation (the material to be
tested is placed under the skin, usually in mice or rats, although
rabbit models are sometimes used), and insertion of the final
device directly at the target location.
Term
Sample assessment
Definition
is to test degree of calcium deposition (for
both in vitro and in vivo experiments).
Term
In histological techniques
Definition
samples are stained and examined
with a light microscope and other methods such as electron
microscopes
Term
Innate response to an implanted material
Definition
is a nonspecific
response.
Term
Acquired immune response to an implanted material
Definition
is a
response to specific portions of the biomaterial (or proteins
adsorbed on the biomaterial) and is mediated by lymphocytes
circulating constantly in the blood and tissues.
Term
Immunotoxicity
Definition
refers to adverse effects on the function of the
immune system or other body systems as a result of alterations
in immune system function
Term
There are four characteristics of acquired immune response
Definition
specificity (B and T cells respond to antigens), diversity, self/nonself recognition, and immunologic memory
Term
There are two types of acquired immunity
Definition
humoral (based
on the actions of antibodies against foreign substances) and cellular (utilizes specialized lymphocytes, or T cells, to detect
altered self cells such as those from viral infections or cancer).
Term
The major histocompatibility complex (MHC) Class I
molecules
Definition
transmembrane glycoproteins that are found on
almost all nucleated cells in conjunction with a smaller protein,
β 2-macroglobulin.
Term
MHC Class II molecules
Definition
transmembrane glycoproteins
having α and β chains.
Term
MHC molecules
Definition
are inherited from both parents (three loci
each) and thus are different from person to person, and should
be tested for organ transplants
Term
Tissue typing
Definition
is to determine how similar the MHC molecules
are between the host and donor
Term
Endogenous antigens
Definition
such as viral proteins or proteins
produced in cancerous cells reside within a host cell
Term
Exogenous antigens
Definition
are produced outside the host cell and
ingested by phagocytosis.
Term
There are two main types of lymphocytes
Definition
B cells and T
cells
Term
B cell maturation
Definition
B cells are processed in bone marrow and
further matured in the peripheral lymphoid tissues (lymph
nodes and spleen).
Term
T cell maturation
Definition
T cells are formed in the bone marrow and
mature in the thymus.
Term
Activation of lymphocytes
Definition
Both T and B cells are ultimately
activated through the presence of antigens
Term
Clonal populations
Definition
are produced by lymphocyte rapid mitosis,
forming a clonal population of cells that all are specific to that
antigen after activation.
Term
There are two types of B cells
Definition
memory B cells (express
membrane-bound antibodies) and effector B cells or plasma
cells (producing soluble antibodies).
Term
There are five main classes of antibodies
Definition
IgA, IgD, IgE, IgG, and
Term
There are four mechanisms for antibodies to remove a
pathogen
Definition
agglutination (multiple large particles with
antigens on their surfaces are bound into a clump by
antibodies), precipitation (it takes place when the complex
of antibody and antigen becomes very large so that they are no
longer soluble), neutralization (antibodies bind and cover the active or toxic sites on a foreign substance), and (4) lysis
(direct attack on the cell membrane of an invading organism by
certain antibodies).
Term
There are two main types of T cells
Definition
Helper T cell (Th), and cytotoxic T cell (Tc).
Term
Th cells
Definition
are those that acquired immune deficiency syndrome
(AIDS) destroys, rendering the AIDS patients defenseless to
diseases.
Term
Effector and memory Th cells
Definition
Once activated, Th cells form a
clonal population including effector and memory Th cells
Term
There are four actions of cytokines that are secreted by effector
Th cells
Definition
stimulation of B cell (growth and differentiation), stimulation of Tc cell proliferation, further stimulation of
Th cell activation, and promotion of chemotaxis and
activation of macrophages
Term
Effector and memory Tc cells (cytotoxic T lymphocytes or short
for CTLs)
Definition
come from Tc cells. CTLs secrete perforins, which
lyse cells by using mechanisms that are similar to the
membrane attack complex of the complement system to be
discussed below.
Term
Complement system
Definition
is a part of innate immunity but it is highly
interrelated with the acquired immune response (it is composed
of over 20 plasma proteins involved in a cascade that ultimately
causes the elimination of foreign elements).
Term
Membrane attack complex
Definition
forms pores with diameters of 70-
100Ǻ on cell membranes to allow continuous leakage of ions
and small molecules to kill foreign cells
Term
Regulation of the complement system
Definition
is needed to confine the
effects of the complement system to a localized area and
prevent host cells from being lysed by mechanisms intended to
kill only foreign pathogens
Term
Effects of the complement system
Definition
Complement system
activation often amplifies the actions of antibodies.
Term
There are several undesired effects of the acquired immune
response
Definition
donor organ rejection, autoimmune disease,
and allergies
Term
“immunocompatibility”
Definition
means compatibility with
the innate immune system
Term
Hypersensitivity reaction
Definition
an allergic reaction, which is an
undesired immune response mediated by the acquired immune
system (even with synthetic biomaterials).
Term
IgE mediated (type I) allergy
Definition
is caused by plasma cells (effector
B cells) that secrete IgE molecules specific for the allergen
Term
Antibody mediated (type II) allergy
Definition
is caused by antibodies
work alone or in connection with the complement system to
destroy cells or platelets presenting a foreign antigen on their
surface
Term
For immune complex mediated (type III) allergy
Definition
the symptoms
may appear days to weeks after original exposure to the antigen
because, in this type of hypersensitivity, both antigen and antibody must be present in the tissue or circulation at the same
time. It is the mechanism of action of autoimmune diseases
such as lupus
Term
T cell mediated (type IV) allergy
Definition
is a delayed-type
hypersensitivity since the symptoms can appear 24-72 hours
after the second contact with the allergen (antigen)
Term
Allergic to polymers
Definition
Evidence of type IV response to polymers
remains controversial (chemical additives used in the
manufacture of latex gloves may cause this type of
hypersensitivity).
Term
Silicon breast implants
Definition
Litigation has been filed alleging that
silicone breast implants caused autoimmune diseases
(destruction of body tissues due to unchecked acquired immune
response) and thus many of the major makers of these implants
decided to withdraw from the market in 1992. Subsequent
settlements cost these companies billions of dollars and one
manufacturer was forced into bankruptcy. However, after years
of study that found no direct link between silicone breast
implants and these diseases, in 2006 the U.S. FDA approved a
new generation of these implants for use in cosmetic surgeries
Term
There are six markers for T and B cells
Definition
cell adhesion and
spreading, cell death, cell migration (lymphocyte
migration inhibition assay that is used to determine if a
lymphocyte is activated), cytokine release, cell surface
marker expression, and cell proliferation (lymphocyte
transformation tests or LTTs)
Term
An unresolved immune response
Definition
will have characteristics
similar to chronic inflammation, but includes the presence of
lymphocytes as well as inflammatory cells
Term
he most common means of
assessment after implantation in an animal model
Definition
is
histology/immunohistochemistry, with an emphasis on
visualizing the amount of lymphocytes present around the
material.
Term
skin testing
Definition
the placement of
possible antigens from the biomaterial on/under the skin to look for localized inflammation
Term
Monitor the immune response
Definition
can be accomplished by taking blood samples from the animal
periodically without euthanizing it
Term
Biomaterials should support all functions of attached cells.
These functions include
Definition
Viability (all cell types, often
associated with adhesion/spreading on substrate); communication (all cell types); protein synthesis (all cell
types); proliferation (some cell types); migration (some
cell types); activation/differentiation (some cell types); and programmed cell death (some cell types).
Term
Protein-surface interaction
Definition
is often nonspecific
Term
Protein-cell interaction
Definition
is often specific (usually occur via
receptor-ligand interactions).
Term
three general types of cytoskeletal elements
Definition
Actin microfibrils, intermediate filaments, and microtubules
Term
Endoplasmic reticulum (ER)
Definition
responsible for protein synthesis
Term
Cell contacts through
Definition
tight junctions (membrane to
membrane contact), ap junctions (small, hydrophilic
channels), and desmosomes (mechanical attachments of two
cells)
Term
Receptor molecules include
Definition
cadheins, selectins, mucins, integrins, and other cell adhesion molecules
(CAMs).
Term
Proteoglycans
Definition
contain carbohydrates (glycan) that take the form
of long chains of polysaccharides (sugars) called
glycosaminoglycans (GAGs).
Term
The chemical structure of the polysaccharide component of the
most common glycosaminoglycans (GAGs) include
Definition
hyaluronic
acid (HA), keratin sulfate (KS), chondroitin/dermatan sulfate
(CS or DS), heparin sulfate (HS), and heparin
Term
Glycoproteins
Definition
are a type of “glue” to link various tissue
components. They are found in the extracellular environment
(ECM).
Term
ECM molecules, particularly collagen and certain types of
proteoglycans
Definition
can be used as biomaterials to reduce unwanted
immune responses and the risk of material “rejection.”
Term
Gene expression can affect the following functions of cells
Definition
cell viability, proliferation, differentiation, and protein synthesis
Term
Cell proliferation has three types
Definition
labile (continuously
differentiate), permanent (terminally differentiated), and stable (between labile and permanent).
Term
Mesenchymal stem cells (MSCs)
Definition
have the potential to
differentiate through a number of different pathways to form
mesenchymal tissues such as bone, cartilage, muscle, tendon,
ligament, and adipose tissue.
Term
Collagen synthesis has the following steps in sequence
Definition
The portion of chromatin coding for collagen becomes less
compact, allowing enzymes that “unzip” the double helix to
separate the DNA strands; Transcription: The enzymes, called RNA polymerases, then
synthesize linear mRNA strands that are complementary to the
collagen gene on the DNA using the base-paring technique.
Every three bases in the mRNA will form a codon for a specific
amino acid (out of a total of 20 different amino acids that are
building blocks for proteins). After fabrication, the mRNA
strand moves out of the nucleus through nuclear pores and enter
the ER in the cell; Translation: In the ER, tRNA (translation RNA), which acts
adaptor molecules and possess binding sites for a specific
amino acid on one end and the mRNA molecule on the other.
The binding site of the tRNA for the mRNA is a series of three
bases known as the anticodon; The process of translation has three stages: initiation,
elongation, and termination. In the initiation process, mRNA
interacts with a small ribosomal subunit and then also with a
larger ribosomal subunit that has two binding sites to hold two
tRNA molecules which assemble amino acids according to the
codons in mRNA. The elongation process will continue the
amino acid assembly until reaching a termination signal in the
mRNA codes, which initiates the termination process. The
termination process will first end the amino acid assembly to
complete the production of the protein, and then dissolve the
ribosomal subunits; Post-translational process: The completed protein (a fully
formed collagen pro-α chain) will move into the ER lumen and
then go through the process in both ER and Golgi to associate
three pro-α chains to form a procollagen molecule. The
procollagen molecules will be secreted into the ECM to further
stabilize the triple-helical structure to form fibril and finally the
fiber assembly.
Term
DLVO theory
Definition
based on Derjaguin, Landau, Verway, and
Overbeek. It is a basic model for cell adhesion to a surface. There are many limitations of the DLVO theory since many
factors have not been included. In addition, the important
receptor-ligand interaction is not considered. The model of receptor-ligand complex concentration over time
is given by a further model: dC/dt = kf*RL - kr*C where kf and kr are
the reaction rates of complex formation and dissociation, and
where R , L, and C represent the concentrations of the free
receptor, free ligand, and receptor-ligand complex,
respectively. However, it is possible to combine these models with the
DLVO theory to make a more accurate prediction of cellsubstrate
adhesion, taking intro account both specific and
nonspecific interactions
Term
cell spreading
Definition
integrin receptors of cell membrane
interact with ligands on the material surface to firmly anchor
the cell in place.
Term
Direct contact assay
Definition
is to test if cells die when directly contact
biomaterials that are toxic to cells
Term
Agar diffusion assay
Definition
is to test if cells die when contact
biomaterials that are toxic to cells through a buffer of agar
layer
Term
Elution assay
Definition
used to determine the cytotoxicity of leachable
molecules found in biomaterials, such as nonreacted monomers
or degradation products. used to determine the cytotoxicity of leachable
molecules found in biomaterials, such as nonreacted monomers
or degradation products. used to determine the cytotoxicity of leachable
molecules found in biomaterials, such as nonreacted monomers
or degradation products. The elution from the biomaterials is added to cell wells and the
cell viability is tested after certain period of time of cell growth,
say, 24 hours, at body temperature (37 degrees centigrade).
Term
Parallel plate flow chamber
Definition
used for testing cell adhesion and
spreading. The number of cells washed away is an indication of
the cell adhesion ability
Term
DNA and RNA assay
Definition
used to determine if there is direct
damage to a cell’s DNA caused by a biomaterial
Term
The reverse-transcription polymerase chain reaction (RT-PCR)
process
Definition
similar to that of PCR, except that the starting
material to be analyzed is mRNA, which needs to have a
reverse transcription to obtain single strand DNA (ssDNA) to
use the normal PCR process.
Term
Northern blotting
Definition
similar to the Southern blotting but it is for
RNA only
Term
immunohistochemistry
Definition
used to quantify and locate
proteins in a thin section of tissue (determine where and how
much specific proteins have been produced or synthesized).
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