G12 bone grafts & subs

Bone Grafting and Bone Graft Substitutes

James Krieg, MD

• “Bone graft material is any implanted material that, alone or in combination with other materials, promotes a bone healing response by providing osteogenic, osteoconductive, or osteoinductive activity to a local site.”

– Muschler and Lane

Functions of Bone Graft• osteoconduction

– provides matrix for bone growth• osteoinduction

– growth factors encourage mesencymal cells to differentiate into osteoblastic lineages

• osteogenesis– transplanted osteoblasts and periosteal cells

directly produce bone• structural support

Types of Bone Grafts

• autogenous bone• allograft bone• osteoconductive synthetics• osteoinductive agents• composites

Autogenous Bone Graft

– “gold standard”• most effective graft material

– limitations• limited supply• donor site morbidity

Types of Bone Grafts• Cancellous

– biologically conducive to bone formation• hydroxyapatite and collagen form osteoconductive

frame• osteogenic potential of stromal cells• together with adjacent blood clot, growth factors are

provided, providing osteoinduction– bone morphogenic proteins (BMP)– transforming growth factor-beta


• Cancellous– little initial structural support– can gain support quickly as bone is formed

Types of Bone Grafts• Cortical

– less biologically active than cancellous bone• less porous, less surface area, less cellular matrix• Prologed time to revascularizarion

– more structural support• can be used to span defects

• Vascularized cortical– more structural support due to early

incorporation– also osteogenic, osteoinductive

• Transported periosteum


• Bone marrow– aspirated– Osteogenic

• osteoprogenitor cells exist in a 1:50,000 ratio to nucleated cells in marrow aspirate

– can be used in combination with an osteoconductive matrix

Bone Graft Substitutes

• Allograft bone– can be cancellous or cortical– plentiful supply– good osteoconductive properties– limited osteoinductive properties– good structural support


• Allograft bone– fresh

• highly antigenic• limited time to test for immunogenicity or diseases• use limited to joint resurfacing


• Allograft bone– fresh frozen

• less antigenic• time to test for diseases

– strictly regulated by FDA

• preserves biomechanical properties– good for structural grafts


• Allograft bone– freeze-dried

• even less antigenic• time to test for diseases

– strictly regulated by FDA

• can be stored at room temperature up to 5 years• mechanical properties degrade• osteoinductive properties slightly preserved


• Ceramics– osteoconductive matrix– mostly hydroxyapatite (HA) , tricalcium

phosphate (TCP)– come in many forms

• porous implants• nonporous dense implants• granular particles


• Ceramics– resorption rates vary widely

• dependant on composition– trade off between rapid resorption (TCP) and structural

support (HA)» combinations of the two often help in this trade-off

• also dependant on porosity, geometry


• Ceramics– resist compression well

• HA more resistant than TCP– brittle

• poor resistance to tension, bending, torque– must protect load bearing until incorporated


• Ceramics– can be used as bone graft extenders– useful for large defects, but need to protect load

bearing until incorporated• can be a lengthy process

– not useful for nonunions where biological activity is needed


• Osteoconductive cement– e.g Norian SRS – provide immediate stability and long term bone

ingrowth– resorption rates can be very slow


• Osteoinductive proteins– bone morphogenic proteins

• BMP-2, BMP-4, BMP-7 (OP-1)• preclinical trials show bone formation in response to

these proteins– other osteotrophic cytokines

• TGF-beta, FGF-2, PDGF, EGF, IGF-1, IGF-11, LMP, and others


• Osteoinductive proteins– BMP bone morphogenetic protein– EGF endothelial growth factor– FGF fibroblast growth factor– IGF insulinlike growth factor– PDGFplatelet derived growth factor– TGF transforming growth factor– LMP LIM-mineralizing protein


• Osteoinductive proteins– delivery directly into graft site– Remaining questions regarding use

• What combination of factors to use?• How to deliver them in appropriate carriers?• How long will they remain biologically active?• Can they cause overactivity? e.g. osteosarcoma


• Osteoinductive proteins– demineralized bone matrix (DBM)

• acid extraction of bone• noncollagenous proteins, bone growth factors, and

collagen• generally poor strength, but can be osteoconductive

and osteoinductive• must be sterilized to prevent disease transmission


• Osteoinductive proteins– can their production be promoted in

mesencymal cells at the desired site?• Genetic therapy

– requires vectors (currently viral vectors exist)– regulation can be a real concern to prevent

overstimulation

Composite Grafts

• Combinations of several techniques and materials can be utilized to take advantage of the strengths of each.

Indications for Bone Graft

• provide structure– metaphyseal impaction

– 27 y.o male with lateral split/depression tibial plateau fracture. Note posterolateral depression.



– ORIF with allograft cancellous bone chips for graft of depressed area.



– 4 months s/p surgery and the graft is well incorporated.


• provide structure– metaphyseal impaction– segmental defect

– 29 y.o male with defect s/p IMN Type IIIB open tibia fracture. Gentamicin PMMA beads were used as spacers and removed.



– s/p bone grafting with iliac crest autograft.



– 14 months after injury, the fracture is healed and the nail removed.



• stimulate healing– nonunions

– 26 y.o. woman with established atrophic nonunion of the clavicle.




– Plating with cancellous iliac crest autograft.




– 6 months after surgery she is asymptomatic.



• stimulate healing– nonunions– arthrodesis

– Failed subtalar arthrodesis




– Repeat fusion with autogenous iliac crest.




– 6 months after surgery, fused successfully

Graft Incorporation• hematoma formation

– release of cytokines and growth factors


– release of cytokines and growth factors• inflammation

– development of fibrovascular tissue



– development of fibrovascular tissue• vascular ingrowth

– often extending Haversian canals




– often extending Haversian canals • focal osteoclastic resorption of graft




– often extending Haversian canals • focal osteoclastic resorption of graft• intramembranous and/or endochondral bone

formation on graft surfaces

Graft Incorporation

• Cancellous bone interface between graft and host bone.

Graft Incorporation

• Cortical allograft strut graft placed next to cortex of host. After 4 years of incorporation.

Graft Incorporation

• Hydroxyapatitematerial after partialincorporation. Graftwas placed one yearago.

Autograft Harvest

• cancellous– iliac crest (most common)

• anterior- taken from gluteus medius pillar• posterior- taken from posterior ilium near SI joint

– metaphyseal bone• often taken near site of implant

– greater trochanter, distal femur, proximal or distal tibia, calcaneus, olecranon, distal radius, proximal humerus

Autograft Harvest

• cancellous– technique

• cortical window made to harvest cancellous graft• can be done with trephine instrument

– drill sleeves– commercially available trephines or “harvesters”– can be percutaneus procedure

Autograft Harvest

• cortical – fibula common donor

• avoid distal fibula to protect ankle function• preserve head to keep LCL, hamstrings intact

– iliac crest• can be harvested in shape to fill defect

Developments: Present and Future

• graft delivery– implants to support structures and supply graft

• spine cages, etc.

– Osteoconductive cements• provide immediate support, promise of resorption

and replacement by native structure


• bioactive proteins– use is well supported in animal studies

• BMP, DBM, TGF all proven in vivo– questions remain regarding optimal mix and

delivery of proteins


• gene therapy– promises to allow pleuripotential mesenchymal

cells to be “turned on” and “turned off” to regulate bone growth by host production of bioactive proteins

– delivery systems a challenge• currently only vectors are viruses, better ones sought

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G12 bone grafts & subs

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