Biocompatibility: Chapter 7 - Exam 2

Front 1

Diffusion of what (and be specific) diffuse from the wound into the surrounding tissues and body fluids?

Back 1

Chemoattractants such as growth factors derived from activated platelets.

Front 2

After diffusion of chemoattractants from the wound into the surrounding tissues, what comes next?

Back 2

Neutrophils, followed by monocytes from circulating blood go to the wound site

Front 3

What happens to growth factors initially released by activated platelets?

Back 3

They're degraded by proteases but are quickly replaced by others

Front 4

Name the other 4 GF released after the initial GF has been degraded. Name the 6 things that release them.

Back 4

1. Epidermal GF
2. Insulin-like GF
3. Fibroblast GF
4. Vascular Endothelial GF

1. Neutrophils 4. Epithelial cells
2. Macrophages 5. Epidermal cells
3. Fibroblasts 6. Endothelial cells

Front 5

What 3 examples are signals received by the cells from their surroundings to activate and or induce expression of cell-membrane receptors?

Back 5

1. Upon contact with other cells
2. During interactions with the ECM
3. By exposure to locally-released growth factors

Front 6

The absence of what may signal both migration and proliferation of cells?

Back 6

Absence of neighboring cells!

Front 7

The absence of neighboring cells may signal what?

Back 7

Migration and proliferation of new cells!

Front 8

What two types of adhesion interactions are critical to the regulation of cell migration and proliferation in wound healing? What 4 example molecules mediate them?

Back 8

Cell-cell and cell-matrix adhesion interactions that are mediated by 1. integrins 3. selectins
2. cadherins 4. immunoglobulins

Front 9

For cell migration to occur, what must occur?

Back 9

Collagen receptors must be downregulated while integrins must be upregulated.

Front 10

What other components are upregulated in connective tissue cells at the wound-edge?

Back 10

Collagenase and other matrix metalloproteinases (cleaves specific subsets of matrix proteins)

Front 11

What released at the wound site initiate mitosis of sedentary connective tissue cells at the wound site?

Back 11

GF!

Front 12

TRUE OR FALSE: We know every signal involved in stopping cell differentiation and proliferation at this stage (Proliferative Phase) of wound healing.

Back 12

FALSE. Little is known.

Front 13

What two things may be involved in stopping cell differentiation and proliferation in the Proliferative Phase of wound healing?

Back 13

Contact inhibition, chemical, and mechanical cues may be involved

Front 14

Besides wound healing and angiogenesis, what 4 things are integrins important to?

Back 14

1. Embryonic development
2. Maintenance of tissue integrity
3. Leukocyte circulation and recruitment
4. Phagocytosis

Front 15

What are Integrins?

Back 15

Cell-membrane adhesion receptors for specific domains (ligands) for collagen, fibronectin, laminin, and vitronectin.

Front 16

Are Integrins heterodimeric or homodimeric? What do they consist of?

Back 16

Heterodimeric consisting of an alpha subunit and a beta subunit

Front 17

The integrin family contains how many alpha subunits and how many beta subunits?

Back 17

16 alpha and 8 beta

Front 18

How many distinct heterodimeric receptors can Integrin form?

Back 18

22

Front 19

What 2 things can a cell do to affect cell interactions with ligands?

Back 19

1. Express 1+ type of integrin receptors
2. can modulate the # and spatial distribution of these receptors

Front 20

What is a well known and much studied integrin ligand?

Back 20

Arginine-Glycine-Aspartic Acid or RGD

Front 21

Integrin receptors at what points provide a direct link ebtween the EC environment and the intracellular proteins of the cytoskeleton?

Back 21

Focal adhesions points!

Front 22

What are Focal Adhesion Points?

Back 22

Points that provide a direct link between extracellular environment and intracellular proteins of the cytoskeleton

Front 23

In terms of focal adhesions, what is crucial to for the process of cell migration?

Back 23

Dynamic formation and disruption of focal adhesions!

Front 24

According to the textbook, what 5 chemical events may occuur when integrin receptors bind ligands?

Back 24

1. stimulation of protein kinase C and the Na/H antiporter
2. Phosphoinositide hydrolysis
3. Tyrosine phosphorylation of the membrane and intracellular proteins
4. changes in the intracellular pH and [Ca2+]
5. Mitogen-activated protein kinase activation

Front 25

What is Outside In signalling?

Back 25

The intracellular signaling that is initiated through integrin receptors binding to an extracellular ligand

Front 26

Along with migration and proliferation, what do cells (mostly fibroblasts) do?

Back 26

Synthesize the ECM proteins that are deposited in an ordered sequence from the margin of the wound inward. (basically, they form a basic ECM)

Front 27

Along with stimulating migration and mitosis of epithelial cells, what does epidermal growth factor also stimulate?

Back 27

Stimulates synthesis of fibronectin (adhesive protein of ECM)

Front 28

Transforming GF Beta stimulates the production of what 3 things by fibroblasts?

Back 28

1. Collagen
2. Fibronectin
3. Glycosaminoglycans

Front 29

What 2 things does platelet-derived growth factor stimulate the production of by fibroblasts?

Back 29

1. Fibronectin
2. Hyaluronic acid

Front 30

What provides the controlling balance in the process of ECM formation?

Back 30

Inhibitors like Interleukin 1 and prostaglandins!

Front 31

What 2 things does the ECM control?

Back 31

Availability as well as bioactivity of GF at the healing wound site

Front 32

What two things stimulate growth of new capillaries into the neotissues? What releases them?

Back 32

1. Fibroblast GF
2. Vascular endothelial cell GF
released by macrophages and endothelial cells in the hypoxic and acidic environment of wound site

Front 33

Neovascularization involves what 3 things?

Back 33

1. Proliferation
2. Maturation
3. Organization
of endothelial cells into capillary tubes

Front 34

When does angiogenesis cease? What else can happen?

Back 34

When the wound site is filled with new tissues or they can disintegrate as a result of apoptosis regulated by various matrix molecules.

Front 35

What is Granulation Tissue?

Back 35

Newly vascularized tissue containing many small blood vessels + cells + components (proteins)

Front 36

TRUE OR FALSE: Macrophages are NOT present in granulation tissue.

Back 36

FALSE. Macrophages ARE present in granulation tissue.

Front 37

The presence of what 2 things indicate early and latter, respectively, stages of granulation tissue development?

Back 37

1. Early - proteoglycans
2. Later - collagen

Front 38

What is the histologic evidence of normal resolution of the inflammatory phase?

Back 38

Granulation tissue!

Front 39

During the latter stages of granulation tissue development, what two things happen?

Back 39

1. Connective tissue is compacted
2. Wound contracts

Front 40

What causes the wound to contract in the latter stages of granulation tissue formation?

Back 40

Contractile function of myofibroblasts (fibroblasts that have assumed the smooth muscle cell phenotype and can produce contractile forces.)

Front 41

What draws the wound margins together and closes the wound?

Back 41

Tugging on myofibroblasts among themselves

Front 42

What may happen to myofibroblasts at the end of wound contraction?

Back 42

Apoptosis!

Front 43

At the latter stages of damaged tissue replacement by neotissue, the cellularity of the wound decreases as a result of what?

Back 43

Cells undergoing apoptosis triggered by unknown signals!

Front 44

What replaces granulation tissue?

Back 44

A relatively acellular scar

Front 45

What events affect the relative amounts of various collagens as well as structural characteristics?

Back 45

Processes that involve changes in collagen synthesis and degradation

Front 46

What control the degradation of collagen in the wound site? What 4 things release them?

Back 46

Proteolytic enzymes released from macrophages, epidermal cells, endothelial cells, and fibroblasts

Front 47

Is normal collagen fibers parallel or in basketweaved arrangement?

Back 47

Basket-weaved! Parallel fibers are weaker = scars!

Front 48

Neutrophils rapidly migrate and predominate at the wound site for how long?

Back 48

The first 1-2 days!

Front 49

Monocyte migration and macrophage accumulation continue for how long?

Back 49

Days to weeks!

Front 50

What are pivotal for the transition from the inflammatory to the proliferative stage of wound healing?

Back 50

Macrophages!

Front 51

When does granulation tissue appear?

Back 51

Within 3-5 days

Front 52

Angiogenesis takes place when?

Back 52

Within first 3-7 days after injury

Front 53

The proliferative/repair phase lasts for how long?

Back 53

Several weeks

Front 54

How long does the remodeling phase last?

Back 54

Up to a couple of years!

Front 55

What 5 things affect Wound Healing outcome?

Back 55

1. Severity of injury
2. Extent of tissue destruction
3. Species
4. Overall Health
5. Age

Front 56

What color wound is indicative of either inflammatory or infection?

Back 56

Yellow!

Front 57

What color is a wound that is undergoing re-epithelialization?

Back 57

Shiny pink!

Front 58

TRUE OR FALSE: In the case of large wounds, all stages of healing could be present at different regions of the wound at one time.

Back 58

TRUE!!!

Front 59

The rate at which healed skin tissue gains tensile strength is slow. What does it parallel?

Back 59

Parallels collagen accumulation and remodeling! (Tensile strength increases as collagen accumulates and remodels.)

Front 60

The maximal strength of scars is only what percentage of normal skin?

Back 60

70%

Front 61

What are 3 explanations for the underlying mechanisms behind chronic nonhealing wounds?

Back 61

1. Impaired matrix formation
2. Inadequate or inactive growth factors
3. Misregulated enzymes like matrix metalloproteinases

Front 62

The presence of what 3 things indicate chronic inflammation?

Back 62

1. monocytes/macrophages
2. Lymphocytes
3. Plasma cells in histological specimens

Front 63

Biomaterials adsorb serum-derived opsonins (such as immunoglobulins and activated complement protein fragments) that mediate what?

Back 63

Mediate subsequent adhesion and activation of neutrophils and macrophages.

Front 64

When implants are involved, does the process of phagocytosis complete? What does this lead to?

Back 64

NO which leads to Frustrated Phagocytosis

Front 65

In an attempt to phagocytose the synthetic material, monocytes and macrophages do what?

Back 65

Fuse and form multinucleated Foreign Body Giant Cells

Front 66

With a few exceptions, what is the end stage of the wound healing process around implants?

Back 66

Fibrous encapsulation!

Front 67

What is Fibrous Encapsulation?

Back 67

A fibrous tissue produced by the host surrounds the implant material/device and isolates them from surrounding biological environments.

Front 68

Fibrous Capsule formation depends on what 3 things?

Back 68

1. Degree of the original trauma
2. The extent of cell death
2. Anatomic location of the injury site

Front 69

The extent of the foreign body response as well as the composition and thickness of the fibrous tissue depend on what 2 things?

Back 69

1. Shape
2. Physical properties of the biomaterial surface

Front 70

What 2 things affect the thickness of the fibrous capsule?

Back 70

1. Presence of mechanical forces
2. Rate of release, accumulation and bioactivity of released chemicals and corrosion products

Front 71

Thin fibrous capsules are associated with what kind of implants?

Back 71

Rounded, non-moving, chemically stable implants.

Front 72

TRUE OR FALSE: Smooth surfaces tend to induce thicker fibrous capsules than do rough or textured surfaces.

Back 72

TRUE!

Front 73

Is thin or thick fibrous tissue formed around sharp corners of implants?

Back 73

THICK fibrous tissue is formed around sharp corners.

Front 74

What other 4 factors affect the wound healing outcome around implants?

Back 74

1. Location of anatomic site of implantation
2. Adequate blood supply at this site
3. preexisting pathological conditions
4. Infections

Front 75

What are the 3 characteristics of an ideal outcome when it comes to implants?

Back 75

1. Timely resolution of wound healing process
2. Attainment of steady state
3. Integration of the implant (without fibrous capsule) into the surrounding tissue

Front 76

Exposure of biomaterials in the wound-healing milieu may cause what 2 things to occur resulting in the release of ions and monomers?

Back 76

Metal corrosion and or polymer degradation!

Front 77

Subsequent chemical activity of metal corrosion and/or polymer degradation of biomaterials may affect what two things?

Back 77

The chemistry and topography of the material surface

Front 78

The type, concentration, and biochemical activity of released compounds may affect what 4 things?

Back 78

1. Inflammation time
2. Impede timely resolution of wound healing
3. Allegic responses
4. Immune reactions

Front 79

Design of biodegradable polymers are usually intended for them to be what?

Back 79

Degraded products to be either biocompatible or already present int he body and thus can be excreted or removed via existing metabolic pathways.

Front 80

What is Foreign-Body Carcinogenesis?

Back 80

Development of tumors at or near the surface of an implanted device

Front 81

Development of foreign-body carcinogenesis depends on what 2 things?

Back 81

1. Physical shape/characteristics of the device
2. End-stage foreign body response to the implant

Front 82

When large defects due to tissue injury do not heal properly, what 3 things are formed?

Back 82

Granulation tissue, fibrosis, and scar tissue

Front 83

What is a normal process by which the body copes with the intrusion of implants?

Back 83

Isolation of implant material and devices by fibrous encapsulation

Front 84

When does the isolated situation become problematic?

Back 84

When infection, bacteria and other microorganisms find haven inside the fibrotic capsule and thrive there untouchable by antibiotics.

Front 85

In the case of subcutaneous implantation, what may happen to the prosthetic device?

Back 85

The isolated prosthetic device may be literally pushed outside the body.

Front 86

If the implanted biomaterial is biodegradable, what can happen to the capsule?

Back 86

It may collapse on resorption of the construct.

Front 87

TRUE OR FALSE: Embryonic wounds do not heal perfectly, they just have more time to heal finely so it's hard to see.

Back 87

FALSE. Embryonic wounds heal perfectly without scarring and with regeneration of lost tissue

Front 88

Do embryonic wounds have conversion of fibroblasts into myofibroblasts?

Back 88

NO! This is why some people think embryonic wounds heal perfectly: no wound contraction.