ch 48 Flashcards
What are the mechanisms of new bone formation
Osteogenesis, osteoinduction, osteoconduction, osteopromotion
What are the most accessible sources of adult stem cells?
Cambium layer of periosteum, bone marrow, and fat
What lines can a mesenchymal stem cell form?
Osteoblastic, chondroblastic, adipocytic, tenocytic, or myoblastic lineages
How do growth factors affect target cells?
Via autocrine, paracrine, or endocrine mechanisms
Define autocrine influences
Influences on cells of similar or identical phenotype in the local environment
Define paracrine influences
Influences on adjacent cells of different phenotype
Define endocrine influence
Influences on different and remote populations of cells
What growth factors are important for osteogenesis?
TGF-β, BMP (-2, -4, -7), FGF-1 and -2, IGF, PDGF
Where is TGF-β especially common?
Bone, platelets, cartilage
When is TGF-𝛽 present?
Thought to play a role throughout entire healing process
Role of BMP?
Can cause ectopic new bone formation
what are experimental applications of BMP
segmental bone defects, nonunions, and spinal fusion
what is needed for BMP to be effective
carrier, otherwise BMP is soluble and rapidly cleared from local enviornment
what are the most efficacious carriers for bmp
absorbable collagen sponge, some types of calcium phosphate
what is the role of fibroblast growth factor
embryologic development, angiogenesis, and proliferation of mesenchymal stem cells
what FGF are most abdundant
FGF 1 and FGF2 from mesenchymal cells and osteoblastic lineage of cells
when is FGF active during fracture repair
early stages of healing and angiogenesis
where is insulin like growth factor released
target cells in the physis of bones
what triggers the release of IGF
GHRH produced in hypothalamus → production of GH in anterior pituitary → travels to physis of bones → stimulates target cells to release IGF
what role does IGF play
facilitates bone and limb lengthening and encourages local cell proliferation
how can gene therapy be introduced
electric pulsation or ultrasonic waves used to translocate into nucleus
viral vectors (adenovirus)
what is an osteogenic graft
graft that directly supplies and supports bone forming cells
what is the best example of osteogenic graft
fresh autogenous cancellous bone graft
what does cancellous autograft supply
variety, fully differentiated osteoblasts lining cancellous bone to undifferentiated mesenchymal cells
what is the survival rate of cancellous autograft
60% of cells remain 3 hours after harvesting
what is the timeline for osteogenesis with cancellous autograft
maximum osteogenesis 8 weeks post transplantation but can start as early as 5 days
what do bone marrow aspirates contain
mesenchymal stem cells (committed to osteogenic or chondrogenic lineage) and some biologically active proteins that stimulate bone regeneration
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
Osteoinductive bone graft
material that has the capacity to induce bone formation when palced into a site where no bone formation will otherwise occur
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
how is autogenous bone graft osteogenic
Trabeculae are lined with osteoblast that provide osteogenesis under influence of local cytokines
how is autogenous bone graft osteoinductive
bone matrix of cancellous bone releases cytokines and growth factors from ECM
how is autogenous bone graft osteoconductive
maintains a structural scaffold that serves as a special conduit where new bone can form
what osteopromotive function does autogenous bone graft have
hemorrhage and resultant clot contains activated platelets and growth factors
where are the most common donor sites for grafts
proximal humerus and wing of ilium
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
what is optional graft size
3mm-6mm
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
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
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
define corticalization
process where over several months lamellar bone leads to new/continuous cortical surface
what is proactive substitution
rapid bone deposition following resorption of necrotic trabeculae associated with autogenous bone graft
what is creeping substitution and when is it seen
cylindrical pattern of vascular invasion and subsequent bone formation and resorption. seen with cortical allografts
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.
what are viable cell elements that evoke an immunogenic reaction
periosteum, muscle, blood cells, and marrow
how do cortical allografts heal
inflammatory response
what is a disadvantage of cortical allografting (related to the healing process)
bone becomes much weaker than host bone during resorption phase of graft
what percentage of bone is calcium
25
what percentage of demineralized bone matrix is calcium
3%
what type of bone healing characteristics does demineralized bone matrix contain
osteoinductive properties
what is the first step of autograft/allograft healing
demineralization to expose BMP and other growth factors
how can you mimic autograft with demineralized bone matrix
mix DBM with patients blood or marrow to increase progenitor cells in allograft
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
What do graft substitutes provide?
Only osteoconductive effects
What are bioceramics?
Ceramics with surface characteristics that become biologically compatible and support bone ingrowth
What is the optimal pore size for ceramic grafts?
300-500microns—allows entry of osteoprogenitor cells
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
