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ch 48 Flashcards

1
Q

What are the mechanisms of new bone formation

A

Osteogenesis, osteoinduction, osteoconduction, osteopromotion

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2
Q

What are the most accessible sources of adult stem cells?

A

Cambium layer of periosteum, bone marrow, and fat

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3
Q

What lines can a mesenchymal stem cell form?

A

Osteoblastic, chondroblastic, adipocytic, tenocytic, or myoblastic lineages

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4
Q

How do growth factors affect target cells?

A

Via autocrine, paracrine, or endocrine mechanisms

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5
Q

Define autocrine influences

A

Influences on cells of similar or identical phenotype in the local environment

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6
Q

Define paracrine influences

A

Influences on adjacent cells of different phenotype

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7
Q

Define endocrine influence

A

Influences on different and remote populations of cells

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8
Q

What growth factors are important for osteogenesis?

A

TGF-β, BMP (-2, -4, -7), FGF-1 and -2, IGF, PDGF

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9
Q

Where is TGF-β especially common?

A

Bone, platelets, cartilage

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10
Q

When is TGF-𝛽 present?

A

Thought to play a role throughout entire healing process

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11
Q

Role of BMP?

A

Can cause ectopic new bone formation

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12
Q

what are experimental applications of BMP

A

segmental bone defects, nonunions, and spinal fusion

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13
Q

what is needed for BMP to be effective

A

carrier, otherwise BMP is soluble and rapidly cleared from local enviornment

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14
Q

what are the most efficacious carriers for bmp

A

absorbable collagen sponge, some types of calcium phosphate

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15
Q

what is the role of fibroblast growth factor

A

embryologic development, angiogenesis, and proliferation of mesenchymal stem cells

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16
Q

what FGF are most abdundant

A

FGF 1 and FGF2 from mesenchymal cells and osteoblastic lineage of cells

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17
Q

when is FGF active during fracture repair

A

early stages of healing and angiogenesis

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18
Q

where is insulin like growth factor released

A

target cells in the physis of bones

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19
Q

what triggers the release of IGF

A

GHRH produced in hypothalamus → production of GH in anterior pituitary → travels to physis of bones → stimulates target cells to release IGF

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20
Q

what role does IGF play

A

facilitates bone and limb lengthening and encourages local cell proliferation

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21
Q

how can gene therapy be introduced

A

electric pulsation or ultrasonic waves used to translocate into nucleus
viral vectors (adenovirus)

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22
Q

what is an osteogenic graft

A

graft that directly supplies and supports bone forming cells

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23
Q

what is the best example of osteogenic graft

A

fresh autogenous cancellous bone graft

24
Q

what does cancellous autograft supply

A

variety, fully differentiated osteoblasts lining cancellous bone to undifferentiated mesenchymal cells

25
Q

what is the survival rate of cancellous autograft

A

60% of cells remain 3 hours after harvesting

26
Q

what is the timeline for osteogenesis with cancellous autograft

A

maximum osteogenesis 8 weeks post transplantation but can start as early as 5 days

27
Q

what do bone marrow aspirates contain

A

mesenchymal stem cells (committed to osteogenic or chondrogenic lineage) and some biologically active proteins that stimulate bone regeneration

28
Q

why is aspirated bone marrow not as useful as bone graft

A

osteoprogenitor cells may be low in the sample; lacks scaffold or osteoconductive material to be efficacious on its own

29
Q

Osteoinductive bone graft

A

material that has the capacity to induce bone formation when palced into a site where no bone formation will otherwise occur

30
Q

what ist he mechanism of osteoinductive bone graft

A

Chemoattraction: recruit mesenchymal stem cells or progeny to infiltrate the material of tissues
Differentiation: induce multipotent cells to multiply and become cells that make up regenerating bony callus

31
Q

how is autogenous bone graft osteogenic

A

Trabeculae are lined with osteoblast that provide osteogenesis under influence of local cytokines

32
Q

how is autogenous bone graft osteoinductive

A

bone matrix of cancellous bone releases cytokines and growth factors from ECM

33
Q

how is autogenous bone graft osteoconductive

A

maintains a structural scaffold that serves as a special conduit where new bone can form

34
Q

what osteopromotive function does autogenous bone graft have

A

hemorrhage and resultant clot contains activated platelets and growth factors

35
Q

where are the most common donor sites for grafts

A

proximal humerus and wing of ilium

36
Q

less common places for bone graft harvesting

A

proximomedial tibia, subtrochanteric region of femur, condyles of the femur, caudoventral portion of the mandible, and the rib

37
Q

what is optional graft size

A

3mm-6mm

38
Q

describe healing of autogenous bone graft: initial 0 - 5 days

A

Within minutes to hours and inflammatory response attracts inflammatory cells, and revascularization and osteoinduction begin

Within 5 days, capillary loops enter the connective tissue

39
Q

describe healing of autogenous bone graft: 5-14 days

A

Necrotic tissue is resorbed and graft is fully vascularized by 2 days
Woven bone will initially be deposited on the necrotic trabeculae of the graft and will later be remodeled into lamellar bone

40
Q

Healing of autogenous bone graft: > 2 weeks

A

Over several months, remodeling of lamellar bone leads to cortical surface (corticalization) and deeper trabecular bone (medulization)
Osteoclastic activation within cancellous bone graft causes resorption of entrapped cores of necrotic graft
The new bone is remodeled into cortical bone in response to mechanical stress

41
Q

define corticalization

A

process where over several months lamellar bone leads to new/continuous cortical surface

42
Q

what is proactive substitution

A

rapid bone deposition following resorption of necrotic trabeculae associated with autogenous bone graft

43
Q

what is creeping substitution and when is it seen

A

cylindrical pattern of vascular invasion and subsequent bone formation and resorption. seen with cortical allografts

44
Q

what characteristics does allogenic bone graft have

A

Osteoinductive: BMP which are exposed through demineralization and facilitate induction of bone growth. Provides osteoconductive scaffold for vascular ingrowth and osteoblast migration.

45
Q

what are viable cell elements that evoke an immunogenic reaction

A

periosteum, muscle, blood cells, and marrow

46
Q

how do cortical allografts heal

A

inflammatory response

47
Q

what is a disadvantage of cortical allografting (related to the healing process)

A

bone becomes much weaker than host bone during resorption phase of graft

48
Q

what percentage of bone is calcium

A

25

49
Q

what percentage of demineralized bone matrix is calcium

A

3%

50
Q

what type of bone healing characteristics does demineralized bone matrix contain

A

osteoinductive properties

51
Q

what is the first step of autograft/allograft healing

A

demineralization to expose BMP and other growth factors

52
Q

how can you mimic autograft with demineralized bone matrix

A

mix DBM with patients blood or marrow to increase progenitor cells in allograft

53
Q

what BMP induce pluripotent transformation to osteoblasts

A

BMP 2, 6, and 9 promote differentiation of pluripotent mesenchymal stem cells to osteoprogenitor lineage

BMP 2, 4, 7, and 9 have roles in differentiation of osteoprogenitor cells to osteoblasts

54
Q

What do graft substitutes provide?

A

Only osteoconductive effects

55
Q

What are bioceramics?

A

Ceramics with surface characteristics that become biologically compatible and support bone ingrowth

56
Q

What is the optimal pore size for ceramic grafts?

A

300-500microns—allows entry of osteoprogenitor cells

57
Q

why do pores have to be interconnected with ceramic grafts

A

Vascular ingrowth cannot occur if pores not interconnected → leading to low oxygen tension environment → stems cells encouraged to follow fibroblastic, chondroblastic, adipoblastic lineage

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