Bone grafts Flashcards
What are some biologic initiators of bone growth?
- Mesenchymal stem cells.
- Growth factors.
- Bone graft
Where are mesenchymal stem cells most readily obtained?
Cambrium of the periosteum, bone marrow and fat.
What are some growth factors that have been investigated for use in bone healing?
- TGF-B: inconsistent results when used for bone healing.
- rh-BMP-2, 4 and 7: most extensively studied. Have been shown to cause ectopic bone formation. Often combined with a collagen sponge carrier.
- FGF-1 and FGF-2: critical role in angiogenesis and proliferation of mesenchymal stem cells.
- Insulin GF: no evidence that exogenous supplementation influences bone healing.
- PDGF: potential efficacy.
What are the four classification strategies of bone grafting, with examples?
Osteogenesis: Autogenous cancellous bone graft (also has osteoinductive, osteoconductive and osteopromotive properties).
Osteoinduction: demineralized bone matrix.
Osteoconduction: anything that provides a scaffold for bone formation, can be absorbable/nonabsorbable, natural/synthetic, may or may not have load bearing properties.
Osteopromotion: PRP, hydrogels, biphasic calcium phosphate
What are the properties of an osteogenic bone graft?
Directly supplies and supports bone forming cells. Autogenous cancellous bone graft supplies a range of cells from fully differentiated osteoblasts lining the cancellous bone to undifferentiated mesenchymal cells in the marrow component.
What is the proportion of cells that survive with autogenous cancellous bone grafting?
60% (up to 3 hours after harvesting)
When does maximum osteogenesis occur after autogenous cancellous bone grafting?
Starts within 5 days, maximum osteogenesis at 8 weeks
Is bone marrow or autogenous bone graft a better osteogenic material?
Autogenous bone graft. Reasons may be: (1) varying quality of bone marrow based on collection technique, (2) lower osteoprogenitor cell content, (3) lack of the necessary scaffold, or osteoconductive material to be efficacious on its own.
What are the properties of an osteoinductive bone graft?
Capacity to induce bone formation when placed at a site where otherwise no bone formation will occur.
Recruit mesenchymal stems cells or their progeny, and then induce them to multiply and become cells that make up the regenerating bony callus.
What is the effect of demineralizing bone matrix?
Decalcification of bone exposes the organic matrix, along with a plethora of bone stimulatory cytokines (including TGF-B, BMP-2, 4, and 7).
What are the properties of an osteoconductive bone graft?
Anything that provides a scaffold for mesenchymal stem cells and their progeny to migrate into and proliferate with. Supply an appropriate framework onto which mesenchymal stem cells, osteoblasts, osteocytes, chondroblasts, and chondrocytes can adhere.
Can be natural (trabecular matrix of cancellous bone) or synthetic (porous bioceramics).
What are the properties of an osteopromotive bone graft?
A material or physical impetus that results in enhancement of regenerating bone (cannot induce bone formation).
What gives autogenous cancellous bone grafts its osteoconductive, osteopromotion, osteogenesis, and osteoinductive properties?
Osteogenesis: trabeculae are lined with osteoblasts that provide osteogenesis under the influence of local cytokines
Osteoinduction: disrupted bone matrix of the cancellous bone releases an entire milieu of cytokines and growth factors.
Osteoconduction: properly harvested graft maintains a structural scaffold
Osteopromotion: hemorrhage and the resulting clot contain activated platelets, and hence growth factors from the released platelet alpha granules, which contain IGF-1, PDGF, and TGF-β
What are the most common sites for autogenous cancellous bone graft collection?
Proximal humerus, wing of the ilium, proximomedial tibia, femoral condyles, subtrochanteric region of the femur
How quickly does restoration occur after autogenous cancellous bone graft collection from the proximal humerus and the proximal tibia?
Humerus: 8-weeks
Tibia: 12-weeks
What is the ideal size of autogenous cancellous bone graft material?
3-6mm
How do autogenous cancellous bone grafts heal?
Proactive substitution: cyclical pattern of vascular invasion, subsequent bone formation and resorption.
Graft is fully vascularized by 20 days.
What are the properties of allograft bone substitutes?
Osteoinductive (exposed BMP through demineralization) and osteoconductive (in its cancellous form).
Have no osteogenetic properties.
Note: Cortical allografts also likely have limited osteoinductive properties.
How do cortical allografts heal?
Creeping substitution: after vascular penetration the bone is slowly resorbed by osteoclastic and immunologic activity and replaced with host bone. Can take months to years.
Process can be enhanced by the addition of an autogenous cancellous bone graft.
What is demineralized bone matrix?
Bone that has been ground to specific particle sizes and has been decalcified with use of acids.
Can be preserved by freezing or freeze drying.
What is the calcium content of demineralized bone matrix?
<3% (22-25% in normal bone)
What classification of bone graft does demineralized bone matrix fall under?
Osteoinductive. If combined with allogenic cancellous bone chips (Orthomix) can have osteoconductive component. Mix with blood/bone marrow at the surgical site to provide cells for osteogenesis.
What are the three methods of mesenchymal stem cell collection for use in bone healing?
1) Culture expanded autogenous.
2) Culture expanded allogenic.
3) Selective mesenchymal stem cell retention.
Mesenchymal stems cells (osteogenic) can be added to a carrier matrix with osteoinductive and osteoconductive properties to maximize effectiveness.
What effect do BMP-2 and 7 have on bone healing?
Stimulate differentiation of osteoprogenitor cells into osteoblasts.
What are some examples of synthetic bone graft substitutes?
Osteoconductive: ceramics, calcium phosphate ceramics, tricalcium phosphate, biphasic calcium phosphate, calcium sulfate, coralline bone graft substitutes.
Hydrogels have been investigated for use in controlled release of proteins and growth factors (FGF, HGF, PDGF, VEGF).
What is the ideal pore size of a ceramic to allow osteoprogenitor cell infiltration?
300-500 um