Bone grafts

Question 1

What are some biologic initiators of bone growth?

Answer 1

1. Mesenchymal stem cells.
2. Growth factors.
3. Bone graft

Question 2

Where are mesenchymal stem cells most readily obtained?

Answer 2

Cambrium of the periosteum, bone marrow and fat.

Question 3

What are some growth factors that have been investigated for use in bone healing?

Answer 3

1. TGF-B: inconsistent results when used for bone healing.
2. rh-BMP-2, 4 and 7: most extensively studied. Have been shown to cause ectopic bone formation. Often combined with a collagen sponge carrier.
3. FGF-1 and FGF-2: critical role in angiogenesis and proliferation of mesenchymal stem cells.
4. Insulin GF: no evidence that exogenous supplementation influences bone healing.
5. PDGF: potential efficacy.

Question 4

What are the four classification strategies of bone grafting, with examples?

Answer 4

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

Question 5

What are the properties of an osteogenic bone graft?

Answer 5

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.

Question 6

What is the proportion of cells that survive with autogenous cancellous bone grafting?

Answer 6

60% (up to 3 hours after harvesting)

Question 7

When does maximum osteogenesis occur after autogenous cancellous bone grafting?

Answer 7

Starts within 5 days, maximum osteogenesis at 8 weeks

Question 8

Is bone marrow or autogenous bone graft a better osteogenic material?

Answer 8

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.

Question 9

What are the properties of an osteoinductive bone graft?

Answer 9

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.

Question 10

What is the effect of demineralizing bone matrix?

Answer 10

Decalcification of bone exposes the organic matrix, along with a plethora of bone stimulatory cytokines (including TGF-B, BMP-2, 4, and 7).

Question 11

What are the properties of an osteoconductive bone graft?

Answer 11

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).

Question 12

What are the properties of an osteopromotive bone graft?

Answer 12

A material or physical impetus that results in enhancement of regenerating bone (cannot induce bone formation).

Question 13

What gives autogenous cancellous bone grafts its osteoconductive, osteopromotion, osteogenesis, and osteoinductive properties?

Answer 13

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

Question 14

What are the most common sites for autogenous cancellous bone graft collection?

Answer 14

Proximal humerus, wing of the ilium, proximomedial tibia, femoral condyles, subtrochanteric region of the femur

Question 15

How quickly does restoration occur after autogenous cancellous bone graft collection from the proximal humerus and the proximal tibia?

Answer 15

Humerus: 8-weeks
Tibia: 12-weeks

Question 16

What is the ideal size of autogenous cancellous bone graft material?

Answer 16

3-6mm

Question 17

How do autogenous cancellous bone grafts heal?

Answer 17

Proactive substitution: cyclical pattern of vascular invasion, subsequent bone formation and resorption.

Graft is fully vascularized by 20 days.

Question 18

What are the properties of allograft bone substitutes?

Answer 18

Osteoinductive (exposed BMP through demineralization) and osteoconductive (in its cancellous form).

Have no osteogenetic properties.

Note: Cortical allografts also likely have limited osteoinductive properties.

Question 19

How do cortical allografts heal?

Answer 19

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.

Question 20

What is demineralized bone matrix?

Answer 20

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.

Question 21

What is the calcium content of demineralized bone matrix?

Answer 21

<3% (22-25% in normal bone)

Question 22

What classification of bone graft does demineralized bone matrix fall under?

Answer 22

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.

Question 23

What are the three methods of mesenchymal stem cell collection for use in bone healing?

Answer 23

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.

Question 24

What effect do BMP-2 and 7 have on bone healing?

Answer 24

Stimulate differentiation of osteoprogenitor cells into osteoblasts.

Question 25

What are some examples of synthetic bone graft substitutes?

Answer 25

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).

Question 26

What is the ideal pore size of a ceramic to allow osteoprogenitor cell infiltration?

Answer 26

300-500 um