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ch 48 Flashcards

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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

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A

fresh autogenous cancellous bone graft

24
Q

what does cancellous autograft supply

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A

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

25
what is the survival rate of cancellous autograft
60% of cells remain 3 hours after harvesting
26
what is the timeline for osteogenesis with cancellous autograft
maximum osteogenesis 8 weeks post transplantation but can start as early as 5 days
27
what do bone marrow aspirates contain
mesenchymal stem cells (committed to osteogenic or chondrogenic lineage) and some biologically active proteins that stimulate bone regeneration
28
why is aspirated bone marrow not as useful as bone graft
osteoprogenitor cells may be low in the sample; lacks scaffold or osteoconductive material to be efficacious on its own
29
Osteoinductive bone graft
material that has the capacity to induce bone formation when palced into a site where no bone formation will otherwise occur
30
what ist he mechanism of osteoinductive bone graft
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
how is autogenous bone graft osteogenic
Trabeculae are lined with osteoblast that provide osteogenesis under influence of local cytokines
32
how is autogenous bone graft osteoinductive
bone matrix of cancellous bone releases cytokines and growth factors from ECM
33
how is autogenous bone graft osteoconductive
maintains a structural scaffold that serves as a special conduit where new bone can form
34
what osteopromotive function does autogenous bone graft have
hemorrhage and resultant clot contains activated platelets and growth factors
35
where are the most common donor sites for grafts
proximal humerus and wing of ilium
36
less common places for bone graft harvesting
proximomedial tibia, subtrochanteric region of femur, condyles of the femur, caudoventral portion of the mandible, and the rib
37
what is optional graft size
3mm-6mm
38
describe healing of autogenous bone graft: initial 0 - 5 days
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
describe healing of autogenous bone graft: 5-14 days
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
Healing of autogenous bone graft: > 2 weeks
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
define corticalization
process where over several months lamellar bone leads to new/continuous cortical surface
42
what is proactive substitution
rapid bone deposition following resorption of necrotic trabeculae associated with autogenous bone graft
43
what is creeping substitution and when is it seen
cylindrical pattern of vascular invasion and subsequent bone formation and resorption. seen with cortical allografts
44
what characteristics does allogenic bone graft have
Osteoinductive: BMP which are exposed through demineralization and facilitate induction of bone growth. Provides osteoconductive scaffold for vascular ingrowth and osteoblast migration.
45
what are viable cell elements that evoke an immunogenic reaction
periosteum, muscle, blood cells, and marrow
46
how do cortical allografts heal
inflammatory response
47
what is a disadvantage of cortical allografting (related to the healing process)
bone becomes much weaker than host bone during resorption phase of graft
48
what percentage of bone is calcium
25
49
what percentage of demineralized bone matrix is calcium
3%
50
what type of bone healing characteristics does demineralized bone matrix contain
osteoinductive properties
51
what is the first step of autograft/allograft healing
demineralization to expose BMP and other growth factors
52
how can you mimic autograft with demineralized bone matrix
mix DBM with patients blood or marrow to increase progenitor cells in allograft
53
what BMP induce pluripotent transformation to osteoblasts
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
What do graft substitutes provide?
Only osteoconductive effects
55
What are bioceramics?
Ceramics with surface characteristics that become biologically compatible and support bone ingrowth
56
What is the optimal pore size for ceramic grafts?
300-500microns—allows entry of osteoprogenitor cells
57
why do pores have to be interconnected with ceramic grafts
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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