Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cell and tissue interaction w/ biomaterials > Quiz > Flashcards

Quiz Flashcards

1
Q

What does the Vroman effect state?

A

“Smaller proteins in higher concentration arrive first and are replaced by larger proteins with higher affinity to the surface”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Types of contacts involved in cell-cell interfaces

A
  • Tight junctions
  • Desmosomes
  • Gap junctions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Types of contacts involved in cell-ECM interfaces

A
  • Hemidesmosomes
  • Focal adhesions (clusters of integrin receptors binding ECM proteins)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Four phases of wound healing

A
  1. Blood coagulation/hemostasis
  2. Inflammation
  3. Repair/proliferation
  4. Remodeling/maturation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How are blood vessels constructed?

A

The blood vessel wall consist of three layers:
- The “intima” is the layer in contact with the blood, consist of endothelial cells connected to the lamina
- The “media” comes second and consist of smooth muscle cells and elastin fibres
- The outmost layer is the “adventia” which is built up by oriented collagen and elastin fibres, and fibroblast cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Types of granules in platelets

A
  • Dense granules (contain ADP, Ca2+, serotonin)
  • Lysosomal granules (contain hydrolytic enzymes)
  • Alpha granules (contain β-thromboglobulin, thrombin, Factor V, and Factor XIII)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happens in/on platelets when they are activated?

A
  • Arachiodonic acid metabolic pathway upregulated
  • Granules contract and their content is released
  • Become “spikey” and “sticky”
  • Increased expression of membrane receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Four control points in the blood coagulation pathway

A
  • Calcium
  • Thrombin
  • Platelet activation
  • Factor X
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Five natural regulators of blood clotting

A
  • Fibrinolysis
  • Heparin
  • Thrombomodulin
  • Prostacyclin (PGI2)
  • Tissue Factor Pathway Inhibitor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Mechanism of fibrinolysis

A

The endothelial cells release Tissue plasminogen activator which turns Plasminogen (trapped in clot) into Plasmin that digests fibrin fibres into fibrin degradation products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Mechanism of heparin

A

Heparin binds to the enzyme inhibitor anti-thrombin III (AT), causing a conformational change that results in its activation through an increase in the flexibility of its reactive site loop. The activated AT then inactivates thrombin, factor Xa and other proteases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Mechanism of thrombomodulin

A

Thrombomodulin functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming a 1:1 stoichiometric complex with thrombin. This raises the speed of protein C activation thousandfold. Activated protein C proteolytically inactivate proteins Factor Va and Factor VIIIa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Function of prostacyclin

A

Is produced in the Arachidonic acid pathway and prevents platelet activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Function of tissue factor pathway inhibitor

A

TFPI prevents initiation of extrinsic pathway of blood coagulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Two ways to prevent blood clot formation on biomaterial surfaces

A
  1. Prevent protein adsorption and platelet activation by e.g., modifying the surface to mimic healthy endothelial cell surface
  2. Immobilize or release bioactive anticoagulants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which are the two separate approaches for assessing protein adsorption?

A
  1. Measure changes in protein composition and concentration in a protein suspension before and after the suspension has been exposed to the biomaterial surface
  2. Measure the amount and type of proteins adsorbed to the biomaterial surface
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are some methods that can be used to analyse protein solution before and after exposure to a surface?

A
  • Colorimetric assays e.g., spectrometer, enzyme induced color change
  • Fluorescent assays that detect intensity of fluorophore
  • ELISA
  • Western blotting (SDS-PAGE)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

ELISA principle

A

Antigens from the sample to be tested are attached to a surface. Then, a matching antibody is applied over the surface so it can bind the antigen. This antibody is linked to an enzyme and then any unbound antibodies are removed. In the final step, a substance containing the enzyme’s substrate is added. If there was binding, the subsequent reaction produces a detectable signal, most commonly a color change. Direct or indirect depending on number of antibodies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are some dry methods that can be used to directly measure adsorbed protein amount and type?

A
  • MS
  • Contact angles
  • ESCA
  • SIMS
  • SEM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are some wet methods that can be used to directly measure adsorbed protein amount and type?

A
  • ATR-FTIR
  • SPR
  • AFM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does SIMS work?

A

SIMS = Secondary Ion Mass Spectrometry

A focused ion beam directed to the biomaterial surface causes the molecules/proteins at the surface to break up while simultaneously being ionized. These fractions (secondary ions) then come off the surface and are analyzed by MS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does ATR-FTIR work?

A

ATR-FTIR = Attenuated Total Reflectance - Fourier Transform Infrared Spectroscopy

The sample is located above a high-refractive index crystal. Infrared light is then shone into the crystal prism. By measuring the wavelengths of the light when it comes out of the crystal you can determine which proteins and molecules that were adsorbed to the surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does SPR work?

A

SPR = Surface plasmon resonance

Single wavelength fixed angle light is shone into a prism located beneath the surface. When the light reaches the prism it will separate the light in different angles (still only one wavelength). After the light reaches the surface it will reflect into a detector. The detector can then see which angles led to light absorbance of the system and from this determine which proteins had adsorbed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are some techniques for measuring cell-biomaterial interactions?

A
  • Microscopy
  • Cell morphology
  • Cell attachment (number) and viability
  • Cell-fate processes (apoptosis, proliferation, differentiation, migration)
  • Cell function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does immunocytochemistry/immunohistochemistry work?

A

A primary antibody is added to the sample section, which then binds to the protein of interest. A labeled secondary antibody is then added that can bind to a portion of the primary antibody. The secondary antibody can be monitored via a variety of means (e.g. radioisotope, fluorophore)

cyto = in cells and culture
histo = in tissue slice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is conformational strength?

A

It is the protein’s resistance to denature. This is for example influenced by strong intramolecular bonds within the protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Which are the four tissue types and where are they found?

A
  • Nervous tissue: present in brain, spinal cord, and nerves
  • Muscle tissue: cardiac muscle, smooth muscle, and skeletal muscle
  • Epithelial tissue: lining of GI tract organs and other hollow organs, skin surface
  • Connective tissue: fat and other soft padding tissue, bone, blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Which are the major components of ECM?

A
  • Fibrous proteins
    o Collagen
    o Elastin
  • Ground substance (gel)
    o Proteoglycans
    o Hyaluronan
    o GAGs
     Hyaluronan
     Keratan sulphate
     Chondroitin sulphate
     Dermatan sulphate
     Heparan sulphate
     Heparin – most negatively charged molecule in the body!
    o Proteoglycans/GAGs also have an additional role in binding and presenting growth factors to cells
  • Matrix glycoproteins – function as “glue” between cells and ECM
    o Fibronectins
    o Laminin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Surface receptors of a platelet

A

The platelet has several different surface receptors such as GPIb and GPIIb/IIIa which are similar to integrin receptors. These can bind to fibrinogen and other proteins containing the RGD sequence: fibronectin, vitronectin, von Willibrand Factor (vWF)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

When are platelets activated?

A

Platelets become activated by contact with collagen, ECM, fibrinogen, vWF, thrombin, soluble molecules ADP, thromboxane A2, damaged tissues, proteins adsorbed to biomaterial surfaces etc.

Platelets become activated by anything that is not the healthy endothelial cell surface!
I.e., anything that is not the innermost layer in blood vessels.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How is the extrinsic pathway initiated?

A

Tissue trauma will lead to release of Tissue Thromboplastin which is a collection of 1) phospholipids on cell membranes/parts of cell membranes from damaged cells, 2) tissue factor (membrane-associated protein). Factor VII is in the blood and can bind to the tissue factor, and this binding leads to Factor X coming along and also becoming anchored to the membrane.

32
Q

How is the intrinsic pathway initiated?

A

When blood comes in contact with foreign surface (i.e., not healthy endothelial cell membrane), Factor XII binds to negatively charged surface and is activated. This is used, together with Platelet Phospholipids Platelet Factor 3, and Factor X, to activate Factor X.
The Platelet Phospholipids Platelet Factor 3 is found in the membrane of activated platelets.

33
Q

Main events occuring during inflammation

A
  • Remove cellular and tissue debris from the wound
  • Destroy any foreign objects (e.g., microorganisms) in the wound
  • Secretion of signalling molecules to attract new cells to the wound to produce new tissue
34
Q

Inflammatory cells

A

Inflammatory cells are a type of white blood cells, called leukocytes. They include monocytes as well as a group of cells called granulocytes (have internal granules) that is made up of eosinophils, basophils, and neutrophils

35
Q

Neutrophils

A

o Involved in acute (initial, early) phase of inflammatory response
o One of the first cells to arrive, migrates into tissue from bloodstream
o Capable of phagocytosis (“cellular eating”)

36
Q

Monocytes/macrophages

A

o Monocytes are immature cells until they leave the bloodstream
o Turn into macrophages when they migrate into tissues: swell, become granular
o Macrophages are involved in the chronic (later, long term) phase of the inflammatory response
o Capable of phagocytosis

37
Q

By which process do neutrophils and monocytes leave the blood stream?

A

Diapedesis/extravasation

38
Q

Examples of chemotactic molecules for leukocytes

A

o Tissue plasminogen activator from endothelial cells
o Kallikrein and prostaglandins from blood coagulation and platelets
o Fibrin degradation products from fibrinolysis
o Cytokines from other activated leukocytes

39
Q

Describe the process of phagocytosis

A

Phagocytes (macrophages and neutrophils) recognize foreign objects via an opsonin complex. A foreign object is first “opsonised” by antibodies and the molecule C3b (C3b binds to antibody that is bound to antigen on object), prior to binding to receptors on phagocyte membrane, thus stimulating phagocytosis

40
Q

What happens with phagocytic cells when they become activated?

A
  1. Undergo a metabolic burst – ROS e.g., superoxide anions, radicals, H2O2, NO formed within phagolysosomes
  2. Upregulate cytokine and growth factor secretion
    a. To attract more neutrophils and macrophages
    b. To attract immune cells, lymphocytes
    c. To attract tissue cells, fibroblasts, to begin tissue repair
41
Q

What two types of phenotypes can activated macrophages take on, and what do they secrete?

A
  • Pro-inflammatory (M1) – promote continued inflammatory response
    o Secretes ROS, enzymes, and chemotactic substances to recruit more macrophages and neutrophils
  • Anti-inflammatory (M2) – promote next phases of wound healing and new tissue formation
    o Secretes growth factors, enzymes, and chemotactic substances to recruit fibroblasts and endothelial cells
42
Q

What is frustrated phagocytosis?

A
  • Caused by very large, or numerous, biomaterial particulates, fibres of high aspect ratio or implant surface
    o Cells cannot completely ingest the foreign object = “Frustrated phagocytosis” (mainly macrophages)
  • Contents of phagolysosomes spill out into ECM and implant surface
    o Kills the phagocyte
    o Attracts new macrophages
  • New macrophages come and try to phagocytose dead cells + biomaterials -> process repeats
43
Q

What are foreign body giant cells?

A
  • Result of frustrated phagocytosis
  • Macrophages fuse together to form very large cells in an attempt to ingest large or many foreign objects
  • Foreign body giant cell (FBGC) forms from fusion of many macrophages
  • Attach to or surround implant surfaces, together with macrophages
  • Activated macrophages and foreign body giant cells secrete cytokines, but also growth factors and enzymes that
    o Call tissue cells, fibroblasts, to the area to begin next phase of wound healing response
    o Activate immune cells (lymphocytes) in the area
44
Q

Which are the main events during the repair phase?

A
  • Formation of granulation tissue
    o Fibroblast cell recruitment, proliferation, and production of ECM
    o Endothelial cell recruitment, formation of new capillaries and blood vessels (angiogenesis)
45
Q

What is granulation tissue and what does it contain?

A

Granulation tissue is a temporary tissue used to fill the injury site and close the wound. Growth factors from inflammatory cells attract fibroblasts which are activated to produce a lot of ECM to form new temporary matrix. Endothelial cells are also attracted and angiogenesis occurs.

Wound contraction also occurs due to some fibroblasts differentiating to myofibroblasts, muscle-like cells that can contract the tissue

46
Q

Which are the main events occuring during the remodelling phase?

A
  • Granulation tissue remodelled to scar tissue, and eventually to proper tissue
  • Foreign body reaction and fibrous capsule formation around implants
47
Q

How is granulation tissue remodelled to scar tissue?

A
  • ECM is remodelled via change in collagen synthesis (type III to type I), degradation of original collagen and deposition of new collagen
  • Collagens arranged in dense parallel bundles
  • After much collagen deposition at wound site by fibroblasts, cell content of new tissue decreases
  • Acellular scar replaces granulation tissue
    o Scar tissue is not as strong and not same structure as original tissue
48
Q

What is a foreign body reaction?

A

Occurs during remodelling phase.

  • Biomaterials adsorb serum proteins (and can become opsonised by adsorption of antibodies to denature proteins and C3b)
  • First neutrophils, then macrophages arrived, experience frustrated phagocytosis
  • Activated macrophages still release enzymes, oxygen radicals despite lack of phagocytosis
  • Macrophages fuse to form FBGCs in an attempt to phagocytize the larger foreign object
  • Presences of macrophages and FBGCs at and around implant surface as long as the implant is in the body = Foreign Body Reaction
49
Q

What is fibrous capsule formation?

A

(Occurs during remodelling phase)

  • Activated macrophages keep calling fibroblasts, which build up a layer of collagen, fibroblasts and endothelial cells/capillaries surrounding macrophage and FBGC layer at the implant surface
  • Granulation tissue does not become remodelled because of continuous secretion of growth factors from macrophages – inflammatory phase takes a long time, or never ends, as in wound healing without implants
  • Continuous recruitment of fibroblasts and production of collagen = fibrous capsule surrounding implant
    o “Walls off” the implant from the body
    o Typical end stage of wound healing around most implants
    o Thickness of fibrous capsule varies depending on implant shape, stiffness, roughness, chemical composition, and the tissue it is placed into
50
Q

What is the complement system?

A

It is a part of the innate immune system and consist of two main pathways that both end in the formation of a membrane attack complex (MAC) that kill foreign cells using osmotic lysis

51
Q

How is the classical pathway initiated?

A

It starts when antibody binds to a foreign (microbial/biomaterial) surface

52
Q

How is the alternative pathway initiated?

A

It starts when activated complement protein C3b binds to a foreign surface (also acts as an opsonin, promoting phagocytosis)

It is the main method of complement activation by biomaterials, especially for biomaterial in contact with blood

53
Q

What are the functions of C3a and C5a?

A
  • Cleaved complement fragments, C3a and C5a, recruit and activate inflammatory cells
    o They are chemotactants for leukocytes
54
Q

How can complement activation at biomaterial surfaces be regulated?

A
  • Regulatory proteins compete for key binding sites or dissociate molecular complexes = “Regulator of complement activation (RCA)” proteins
  • Host cells have membrane associated constituents that deactivate C3b = “Decay Accelerating Factor (DAF)”, binds C4b & C3b
    o Prevents formation of C3 convertase at the host cell surface
  • By increasing the surface hydrophilicity (using e.g., PEG) or reducing amount of nucleophiles (electron donors) at the surface, you can limit C3b deposition
  • Induce C5a binding to surface by adding negatively charged surface groups (binding leads to it no longer functioning as a chemotactant)
  • Immobilize RCA proteins at biomaterial surface
55
Q

What two types of immunity does the adaptive immune system consist of?

A
  • Cell-mediated immunity
  • Humoral immunity
56
Q

What is cell-mediated immunity and how is it initiated?

A
  • Mediated by T cells
  • Several sub-types of T cells
  • Initiated when T helper cell binds to a foreign antigen via surface receptors
  • Leads to activation of T helper cells, T cytotoxic cells, and formation of memory cells
  • Helper T cells and cytotoxic T cells clone themselves into many memory T cells that remain in tissues for years to respond to next exposure to antigen
  • When cytotoxic T cells bind cells displaying antigen + Class I MHC, they secrete perforins (creates holes in cell membranes), secrete toxins into cytoplasm. The receptor-antigen then disengage, and cytotoxic T cells moves on to next infected cell
57
Q

How does antigen presentation work?

A
  • T cells only recognise antigens expressed on surfaces of antigen-presenting cells (APCs)
  • Antigen is presented together with a major histocompatibility complex (MHC) protein
    o Class II MHCs – T helper cells
    o Class I MHCs – T cytotoxic cells
  • The APCs also secrete cytokines that activate T and B cells
  • The lymphokine release also activates macrophages, accumulate and increase phagocytosis, and act as chemotactic agents, proliferation of cytotoxic T cells, activation and proliferation of B cells
58
Q

How does humoral immunity work and how is it mediated?

A
  • Mediated by B cells
  • Production of antibodies that are antigen-specific
  • No MHC required
59
Q

What are some functions of antibodies?

A
  • Neutralization of microbes and toxins
  • Opsonization and phagocytosis of microbes
  • Lysis of microbes
  • Complement activation
60
Q

What is a hypersensitivity reaction?

A

It is an allergic response to biomaterials.
* Released substances from implants act as haptens – complex with native proteins
* Expressed by/taken up by MHCII receptor on surface of APC
* Native protein + hapten (e.g., metal ion) together then activate immune response via activating T helper cells

61
Q

What is neoplasia?

A

Excessive and uncontrolled cell proliferation

62
Q

What are tumors comprised of?

A

Proliferating neoplastic cells, surrounding connective tissue and blood vessels

63
Q

What is a carcinogen?

A

A stimulus that causes malignant transformation of cells due to many cumulative mutations in DNA of normal cells

64
Q

Which are the three phases of tumor formation?

A
  • Initiation phase - malignant transformation occurs
  • Latency period - can be 15-20 years, no tumors visible
  • Promotion stage - obvious tumor growth observed
65
Q

Which are the two different routes of malignant transformation?

A
  • Chemical carcinogenesis (caused by leachable substances from implant)
  • Foreign body carcinogenesis (pre-neoplastic cells become trapped between implant and fibrous capsule, tumor grows in this “protected space”)
66
Q

What is the mechanism of pathological calcification?

A

Adsorbed negatively charged proteins at biomaterial surface bind calcium ions and nucleate calcium phosphate mineral formation.

Or, remnants of ruptured cells expose negatively charged membrane phospholipids that nucleate mineralisation.

67
Q

What are some implants that become affected by calcification?

A

Heart valves, blood pumps, urinary prosthesis, contact and intraocular lenses

  • Implants with moving parts
  • Implants placed in high salt concentrations
68
Q

How do bacterial adhesion on biomaterials occur (forces etc)?

A
  • Long range, non-specific interactions: vdW, electrostatic, hydrophobic interactions
  • Short range, specific interactions: Adhesin molecules on ends of fimbrae and/or bacteria surface bind to proteins adsorbed at biomaterial surfaces
  • Microbial surface components recognising adhesive matrix molecules (MSCRAMMs) mediate adhesion to ECM proteins, e.g., fibronectin, fibrinogen, laminin, collagen adsorbed at biomaterial surfaces
69
Q

What is quorum sensing?

A

It’s a method of communication between bacteria that enables the coordination of group-based behaviour based on population density

Thisis how bacteria change phenotype from planktonic (single cell) state to biofilm state

70
Q

What is the pathogenesis of BAI?

A

It is a race for the surface: tissue cell integration and bacterial adhesion compete to colonize the implant’s surface.
* If the host tissue “wins” the race, they will defend the implant surface from invading pathogens by implant integration and immune defense
* If bacteria “win”, they will colonize the implant which is the prelude to BAI

71
Q

What do biofilms consist of?

A

A biofilm is a community of bacterial cells + their secreted extracellular polymeric substances (EPS = polysaccharides + extracellular DNA + supportive proteins)

72
Q

What bacteria cause the majority of BAI?

A

Staphylococci

73
Q

What is the treatment of BAI?

A
  • sophisticated diagnostics
  • long-term antimicrobial therapy
  • repetitive surgeries
74
Q

Acute infection

A

Bacteria are in the planktonic state (free floating, individual cells)

75
Q

Chronic infection

A

Bacteria have formed a biofilm, have different growth rates and transcription than planktonic bacteria

Cell and tissue interaction w/ biomaterials (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions