Chapter 48: Bone Grafts and Substitutes Flashcards
What lineages of differentiation are possible for mesenchymal stem cells?
- Osteoblastic
- Chondroblastic
- Adipocytic
- Tenocytic
- Myoblastic
Where are the most accessible sources of mesenchymal stem cells?
- Cambium layer of the periosteum
- Bone marrow
- Fat
What are the three mechanisms via which growth factors act on target cells?
Autocrine: influences on cell of identical or similar phenotype in local environment
Paracrine: Influences seen in adjacent cells of different phenotype
Endocrine: Influences seen in different and remote populations of cells
List the (5) main growth factors in relation to bone production:
Transforming growth factor-Beta (TGF-B)
Bone morphogenic proteins (mostly BMP-2, -4, -7)
Fibroblast growth factor
Insulin-like growth factor
Platelet-derived growth factor
In what tissues is TGF-B most commonly found?
- Bone
- Platelets
- Cartilage
From what superfamily are bone morphogenic proteins (BMP) part of?
Transforming growth factor family
What is the main role of fibroblast growth factor?
What are the most abundant forms in the adult?
- Critical role in angiogenesis and proliferation of mesenchymal stem cells (embryologically important)
- FGF-1 and FGF-2
What is the role is insulin-like growth factors?
- Facilitate bone and limb lengthening and cellular proliferation
CRITICAL to skeletal development
Where is platelet-derived growth factor released from?
The alpha granules of platelets
What is gene therapy?
How it is delivered?
- The introduction of genetic material via noncellular or cellular material
- Introduced by physical mechanisms (electric pulsed or ultrasonic waves) or by viral vectors
What are the basic tenets of bone regeneration and grafting?
Osteogenesis: directly supplies and supports bone-forming cells
Osteoinduction: capacity to induce bone formation when placed into a site where no bone formation will otherwise occur
Osteoconduction: Provides a scaffold for mesenchymal stem cells and their progeny to migrate into and proliferate
Osteopromotive: A material or physical impetus that results in enhancement of regenerating bone
What are the 2 main forms of osteogenic material?
Autogenous cancellous bone graft
Bone marrow (not the same magnitude of osteogenesis)
What percentage of cells in autogenous cancellous bone graft survive at room temperature in normal saline for up to 3hr after harvesting?
When does maximum osteogenesis from autogenous cancellous bone graft occur?
- 60%
- Maximum osteogenesis at 8wk
What is the most common form of osteoinductive agent?
How does it function?
What growth factors are present in the above agent?
- Demineralised bone matrix
Function:
- Recruit mesenchymal stem cells (chemoattraction and migration)
- Induce multipotent cells to multiply and become cells that make up the regenerating bony callus (proliferation and differentiation
Growth factors:
- TGF-B
- BMP-2, -4, -7
What are the characteristics of an osteoconductive agent?
Offer a scaffold for adherence of mesenchymal stem cells, osteoblasts, osteocytes, chondroblasts and chondrocytes with interconnecting porosity for cellular proliferation and, most important, vasular ingrowth
List some (3) examples of osteopromotive materials:
PRP
Hydrogels
Biphasic calcium phosphate
Cannot induce bone formation alone - is just enhancing
How does autogenous cancellous bone graft provide all the tenets of new bone formation?
Osteogenesis - Provided trabeculae lined with osteoblasts
Osteoinduction - cytokines and growth factors within the extracellular matrix
Osteoconduction - maintains a structural scaffold
Osteopromotive - hemorrhage and the resulting clot contain activated platelets and therefore growth factors from the alpha granules (IGF-1, PDGF, TGF-B)
How long do you need to wait before reharvesting bone graft from the proximal humerus and the proximal tibia?
Humerus: 8 weeks
Tibia: 12 weeks
What type and size of curette is recommended for cancellous bone graft harvesting?
- Brun or Spratt Volkmann curette
- Size #000 - #2 (equates to cancellous particles between 3 and 6mm)
How much can a properly applied autogenous cancellous graft speed up healing?
By as much as 4 weeks
Describe the healing process of an autogenous cancellous bone graft:
Minutes-hours: inflammatory response attracts lymphocytes, plasma cells, and mononuclear cells
5 days: Capillary loops enter
20 days: Necrotic tissue is resorbed and graft is fully vascularized
- Woven bone initially placed which is remodeled over several months into lamellar bone
- Remodeling of lamellar bone leads to corticalization
- Remodeling of deeper trabecular bone leads to medulization
What is the method of choice for final sterilisation of allogenic bone graft materials?
low-dose gamma irradiation (less than 2.5mrad)
What is creeping substitution?
Method by which cortical allografts heal
- Haversian systems of the graft are not available for host integration
- Host vascular penetration slowly resorbs cortical allograft by immunologic and/or osteoclastic activity
- Substituted with host bone
- Takes months to years
What is demineralized bone matrix?
Bone which has been ground to specific particle sizes and has been decalcified with the use of acids (typically hydrochloric acid)
- Decreases Ca content from 22-25% to less than 3%
- Osteoinductive material
- Can be mixed with cancellous bone chips for osteoconduction and with patients own blood for osteopromotion
What are three strategies associated with stem cells for bone regeneration?
- Cultured and expanded autologous stem cells
- Cultured and expanded allogenic stem cells
- Selective mesenchymal stem cell retention
Which BMPs promote differentiation of mesenchymal stem cells to an osteoprogenitor lineage?
Which promote differentiation of osteoprogenitor cells into osteoblastic cells?
- Differentiation into osteoprogenitor cells : BMP-2, -6, -9
- Differnetiation into osteoblastic cells: BMP-2, -4, -7, -9
List some examples of bone graft substitutes:
Ceramics
Calcium phosphate ceramics (modelled off hydroxyapatite)
Coralline substitutes (marine coral, treated to convert calcium carbonate to hydroxyapatite)
Tricalcium phosphate (old school, Rapidly absorbed)
Biphasic calcium phosphate (combination of tricalcium phosphate and hydroxyapatite)
Nanocrystalline calcium phosphate
Calcium sulfate (plaster of Paris, rapid absorption)
Hydrogels (polymers containing aqueous solvent capable of controlled release of incorporated proteins such as growth factors
