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Biology of Bone Grafts
1. BIOLOGY OF BONE GRAFTSBIOLOGY OF BONE GRAFTS
Dr Gaurav SinghDr Gaurav Singh
Central Institute ofCentral Institute of
OrthopaedicsOrthopaedics
VMMC & SJHVMMC & SJH
2. Types of Bone GraftTypes of Bone Graft
• AutograftAutograft
• AllograftAllograft
• XenograftXenograft
• Isograft: From one twin to otherIsograft: From one twin to other
Site of transferSite of transfer
• Orthotopic- to anatomically appropriate siteOrthotopic- to anatomically appropriate site
• Heterotopic- anatomically dissimilar siteHeterotopic- anatomically dissimilar site
3. Types of Bone GraftTypes of Bone Graft
• CorticalCortical
• CancellousCancellous
• Cortico-CancellousCortico-Cancellous
• OsteochondralOsteochondral
VascularityVascularity
• VascularizedVascularized
• Non VascularizedNon Vascularized
4. Biological activity of Bone GraftBiological activity of Bone Graft
• OsteogenesisOsteogenesis
• Mechanical SupportMechanical Support
Three Processes required for BoneThree Processes required for Bone
RegenerationRegeneration
• OsteoinductionOsteoinduction
• OsteoconductionOsteoconduction
• Osteogenic CellsOsteogenic Cells
5.
6. OsteoinductionOsteoinduction
• Provides Osteogenic potential by inducingProvides Osteogenic potential by inducing
host bed to synthesize new bonehost bed to synthesize new bone
• Recruitment of mesenchymal cells-Recruitment of mesenchymal cells-
differentiate initially into cartilage- then bonedifferentiate initially into cartilage- then bone
forming cellsforming cells
• Through the recruitment of graft-derivedThrough the recruitment of graft-derived
proteins that drive this physiological process.proteins that drive this physiological process.
7. BMPsBMPs
• Low Molecular Weight PeptidesLow Molecular Weight Peptides
• Most Active- BMP 2,4,7Most Active- BMP 2,4,7
• Differentiate stem cells into OsteoblastsDifferentiate stem cells into Osteoblasts
• Fracture healing and bone remodelingFracture healing and bone remodeling
• ARE PRESENT IN BONE MATRIX,ARE PRESENT IN BONE MATRIX,
VIABLE CELLS NOT NECESSARYVIABLE CELLS NOT NECESSARY
• Present in Both Auto and AllograftPresent in Both Auto and Allograft
• Destroyed by AUTOCLAVINGDestroyed by AUTOCLAVING
8. Bone Graft IncorporationBone Graft Incorporation
• Interaction of Osteoinduction andInteraction of Osteoinduction and
OsteoconductionOsteoconduction
• Creeping SubstitutionCreeping Substitution
• Replacement of the graft by host bone in aReplacement of the graft by host bone in a
predictable pattern under the influences of loadpredictable pattern under the influences of load
bearingbearing
10. Bone Graft IncorporationBone Graft Incorporation
• Initial Inflammatory Response- InflammatoryInitial Inflammatory Response- Inflammatory
cells and Fibroblasts- Cytokines, Growth Factorscells and Fibroblasts- Cytokines, Growth Factors
• Osteoinduction-Osteoinduction- Chemotaxis, mitosis, andChemotaxis, mitosis, and
differentiation of the host osteoprogenitor cellsdifferentiation of the host osteoprogenitor cells
• Chondrocytes –Day 5Chondrocytes –Day 5
• Osteoblasts- Day 10Osteoblasts- Day 10
• Host blood vessels invade the graft throughHost blood vessels invade the graft through
Haversian and Volkmann canalsHaversian and Volkmann canals
• Osteoclasts resorb the surfaces of the graftOsteoclasts resorb the surfaces of the graft
11.
12. Bone Graft IncorporationBone Graft Incorporation
• Intramembranous and Endochondral boneIntramembranous and Endochondral bone
formation usually occurs on graft surfacesformation usually occurs on graft surfaces
• Osteoconduction proceeds in large cortical orOsteoconduction proceeds in large cortical or
cancellous grafts for many years- resorption ofcancellous grafts for many years- resorption of
original graft tissue and replacement with neworiginal graft tissue and replacement with new
host bonehost bone
13. Bone Graft IncorporationBone Graft Incorporation
• Remodeling is a response to weight bearingRemodeling is a response to weight bearing
• Balance between Revascularization,Balance between Revascularization,
Osteogenesis and Graft Response to appliedOsteogenesis and Graft Response to applied
loadsloads
• Bone graft incorporation is a dynamicBone graft incorporation is a dynamic
interplay of the biological function of the boneinterplay of the biological function of the bone
graft, the graft environment, and the host–graftgraft, the graft environment, and the host–graft
mechanical interactions.mechanical interactions.
14. Biology of Bone GraftsBiology of Bone Grafts
• Autografts incorporated earlier and moreAutografts incorporated earlier and more
completelycompletely
• Morbidity and limit of quantityMorbidity and limit of quantity
• Allografts- Prolonged remodelingAllografts- Prolonged remodeling
• Difficult to define the absolute end point ofDifficult to define the absolute end point of
incorporationincorporation
15. Autograft-CancellousAutograft-Cancellous
• Revascularization of the graft occurs rapidlyRevascularization of the graft occurs rapidly
and is characterized by considerable capillaryand is characterized by considerable capillary
ingrowthingrowth
• Both osteoclasts and osteoblast precursors areBoth osteoclasts and osteoblast precursors are
seen earlyseen early
• Osteoconduction proceeds rapidlyOsteoconduction proceeds rapidly
• Incorporation complete by one year- graftIncorporation complete by one year- graft
replaced by host bonereplaced by host bone
16. Autograft-CorticalAutograft-Cortical
• Because of the density of cortical bone-Because of the density of cortical bone-
decreased rate of revascularization anddecreased rate of revascularization and
remodelingremodeling
• Vascular penetration of graft by host tissueVascular penetration of graft by host tissue
occurs only after resorption of dense corticaloccurs only after resorption of dense cortical
surface by osteoclasts is initiatedsurface by osteoclasts is initiated
• Slow Revascularization-Low strength- maySlow Revascularization-Low strength- may
last for months to yearslast for months to years
17. Autograft-CorticalAutograft-Cortical
• Uncoupling between osteoclasts and osteoblastsUncoupling between osteoclasts and osteoblasts
• Osteoclasts can resorb bone at a rate of 50 μm/d,Osteoclasts can resorb bone at a rate of 50 μm/d,
whereas osteoblasts can synthesize new bonewhereas osteoblasts can synthesize new bone
tissue at a rate of only 1 μm/dtissue at a rate of only 1 μm/d
• Lack of immediate blood supply inLack of immediate blood supply in
nonvascularized cortical autograft leads to thenonvascularized cortical autograft leads to the
death of most of the graft’s osteocytesdeath of most of the graft’s osteocytes
• No osteoinduction but osteoconductionNo osteoinduction but osteoconduction
continuescontinues
18. Autograft-Cortical VascularizedAutograft-Cortical Vascularized
• Provide an immediate blood supply andProvide an immediate blood supply and
experience only a transient ischemiaexperience only a transient ischemia
• 50% reduction in failure rate when these grafts50% reduction in failure rate when these grafts
are used to reconstruct defects larger than 6 cmare used to reconstruct defects larger than 6 cm
in lengthin length
• Over 90% of the donor osteocytes may surviveOver 90% of the donor osteocytes may survive
the transplantationthe transplantation
• Uncoupling of bone resorption and formationUncoupling of bone resorption and formation
is diminished.is diminished.
• Stronger than Nonvascularized in 1Stronger than Nonvascularized in 1stst
3 months3 months
19. AllograftAllograft
• ImmunogenicImmunogenic
• Higher Failure RateHigher Failure Rate
• MHC Alloantigens- Mainly MHC IMHC Alloantigens- Mainly MHC I
• Recognized by Host T cellsRecognized by Host T cells
• When histocompatibility differences areWhen histocompatibility differences are
reduced by either matching tissue types orreduced by either matching tissue types or
modifying allografts to reduce immunogenicity,modifying allografts to reduce immunogenicity,
allograft acceptance is improvedallograft acceptance is improved
20. Allograft-CancellousAllograft-Cancellous
• Frozen and Freeze Drying- ImproveFrozen and Freeze Drying- Improve
IncorporationIncorporation
• Revascularization and Remodeling delayed asRevascularization and Remodeling delayed as
compared to Autograftscompared to Autografts
• Osteoinduction and Conduction preservedOsteoinduction and Conduction preserved
• Decalcification and Demineralization- Loss ofDecalcification and Demineralization- Loss of
mechanical strengthmechanical strength
21. Allograft-CorticalAllograft-Cortical
• Transplantation of cortical allografts free ofTransplantation of cortical allografts free of
marrow and blood products has resulted inmarrow and blood products has resulted in
safe outcomessafe outcomes
• Frozen, Freeze DriedFrozen, Freeze Dried
• Cortical allografts may be substantially weakerCortical allografts may be substantially weaker
than autografts for as long as 2 yr after surgerythan autografts for as long as 2 yr after surgery
22. Allograft-CorticalAllograft-Cortical
• Freeze drying reduces the mechanicalFreeze drying reduces the mechanical
properties of the graft and results in aproperties of the graft and results in a
significantly weaker graftsignificantly weaker graft
• Sterilization of bone by irradiation of moreSterilization of bone by irradiation of more
than 30 kGy may destroy any osteoinductivethan 30 kGy may destroy any osteoinductive
functionfunction
• Chemosterilized, autolyzed, antigen-extractedChemosterilized, autolyzed, antigen-extracted
allogeneic bone, although providing inductiveallogeneic bone, although providing inductive
capabilities, has little strengthcapabilities, has little strength
23. To improve Incorporation ofTo improve Incorporation of
Cortical AllograftCortical Allograft
• Perforation of the graft from a biologicalPerforation of the graft from a biological
standpoint increases the available surface areastandpoint increases the available surface area
for ingrowth and ongrowth of new bonefor ingrowth and ongrowth of new bone
• Provides easier access to the intramedullaryProvides easier access to the intramedullary
canalcanal
• Early RevascularizationEarly Revascularization
• Porous because of more area for osteoclastPorous because of more area for osteoclast
resorptionresorption
24. Biomechanics of Bone GraftsBiomechanics of Bone Grafts
• The intrinsic properties of the graft are aThe intrinsic properties of the graft are a
function of its geometry as well as itsfunction of its geometry as well as its
composition and includes properties such ascomposition and includes properties such as
fracture toughness, yield strength, and itsfracture toughness, yield strength, and its
elastic moduluselastic modulus
• A bone graft must be biologically incorporatedA bone graft must be biologically incorporated
into the host in order to function successfullyinto the host in order to function successfully
in load bearingin load bearing
25. Biomechanics of Bone GraftsBiomechanics of Bone Grafts
• Porosity, is related directly to the stiffness ofPorosity, is related directly to the stiffness of
the tissue (as a third power of porosity) andthe tissue (as a third power of porosity) and
yield strength (as a second power of porosity)yield strength (as a second power of porosity)
• Small changes in porosity result in largeSmall changes in porosity result in large
changes in the material properties of bonechanges in the material properties of bone
• Cortical bone grafts initially may have as littleCortical bone grafts initially may have as little
as 5–10% porosityas 5–10% porosity
• Porosity of cancellous grafts may be as high asPorosity of cancellous grafts may be as high as
70–80%,70–80%,
26. Biomechanics of Bone GraftsBiomechanics of Bone Grafts
• The strength of cancellous bone graftsThe strength of cancellous bone grafts
increases as new bone is laid down on theincreases as new bone is laid down on the
preexisting trabecula. However, until the newpreexisting trabecula. However, until the new
graft is successfully integrated into the host, itgraft is successfully integrated into the host, it
is critical that fixation methods sustain ais critical that fixation methods sustain a
significant portion of the loadsignificant portion of the load
27. Biomechanics of Bone GraftsBiomechanics of Bone Grafts
• It is important to achieve a balance betweenIt is important to achieve a balance between
appropriately protecting the graft during theappropriately protecting the graft during the
remodeling phase while allowing the boneremodeling phase while allowing the bone
graft to experience physiological loadsgraft to experience physiological loads
necessary for remodeling to occurnecessary for remodeling to occur
28. Factors InfluencingFactors Influencing
Biomechanics of GraftsBiomechanics of Grafts
• Freezing-Freezing- Minimal EffectMinimal Effect
• Freeze Drying-Freeze Drying- Significantly reduces YieldSignificantly reduces Yield
Strength and StiffnessStrength and Stiffness
• AutoclavingAutoclaving-- dose-dependent decrease in bothdose-dependent decrease in both
strength and stiffness of bonestrength and stiffness of bone
• IrradiationIrradiation- virucidal doses (>30kGy) reduce- virucidal doses (>30kGy) reduce
material properties of graftmaterial properties of graft
• Complete demineralizationComplete demineralization- Reduces- Reduces
immunogenicity but loss of material propertiesimmunogenicity but loss of material properties
29. The ultimate success of any boneThe ultimate success of any bone
graft, however,graft, however,
requires a balance between itsrequires a balance between its
biological functions andbiological functions and
biomechanical propertiesbiomechanical properties
30. PrerequisitesPrerequisites
• A clean, well-vascularized host bed is criticalA clean, well-vascularized host bed is critical
in providing the satisfactory host environmentin providing the satisfactory host environment
• Wide excision of scar tissue, treatment ofWide excision of scar tissue, treatment of
infection, protection of the blood supply, andinfection, protection of the blood supply, and
satisfactory soft tissue coverage is mandatorysatisfactory soft tissue coverage is mandatory
• Selection of appropriate graft material for theSelection of appropriate graft material for the
desired clinical functiondesired clinical function
• Bone graft must also be protected from fullBone graft must also be protected from full
weight bearing until remodeling enables it toweight bearing until remodeling enables it to
function fully in a loaded environmentfunction fully in a loaded environment