4. MECHANISMS
• Osteoconduction
– Provides matrix for bone growth
• Osteoinduction
– Growth factors encourage mesenchymal cells to
differentiate into osteoblastic lineages
• Osteogenesis
– Transplanted osteoblasts and periosteal cells
directly produce bone
5. OSTEOCONDUCTION
• This process supplies the three-dimensional
configuration as a sca old for the ingrowthff
into the graft of host capillaries,
perivascular tissue and osteoprogenitor cells
from the recipient.
6. OSTEOINDUCTION
• possess a chemical matrix, which provides
molecular signals to the host that recruit or
stimulate cellular activity for bone
regeneration.
• The signals are the bone morphogenetic
protein (BMPs), transforming growth
factors (TGFs), platelet-derived growth-
factor (PDGF).
8. • This new bone initially may be important
for the development of callus during early
graft incorporation.
9.
10. TYPES OF BONE GRAFTS
• Autograft
• Allograft
• Bone graft substitutes
– Most have osteoconductive properties
• Osteoinductive agents
– rhBMP-2 (Infuse) and rhBMP-7 (OP-1)
12. AUTOGENOUS BONE GRAFT
• “Gold standard”
• May provide osteoconduction,
osteoinduction and osteogenesis
• Drawbacks
– Limited supply
– Donor site morbidity
13. CORTICAL BONE GRAFTS
• Less biologically active than cancellous bone
– Less porous, less surface area, less cellular matrix
– Prologed time to revascularizarion
• Provides more structural support
– Can be used to span defects
• Vascularized cortical grafts
– Better structural support due to earlier incorporation
14. CANCELLOUS BONE GRAFTS
• Three dimensional scaffold
(osteoconductive)
• Osteocytes and stem cells (osteogenic)
• A small quantity of growth factors
(osteoinductive)
• Little initial structural support
• Can gain support quickly as bone is formed
15. VASCULARIZED GRAFTS
• Bone is transferred with its blood supply
which is anastomosed to vessels at recipient
site.
• Available donor sites:
o Iliac crest (with one circumflex artery)
o Fibula (peroneal artery)
o Radial shaft (interosseus artery)
16. • Vascularized grafts remain completely
viable and incorporated like that of fracture
healing
17. AUTOGRAFT HARVEST
• Cancellous
– Iliac crest (most common)
• Anterior- taken from gluteus medius pillar
• Posterior- taken from posterior ilium near SI joint
– Metaphyseal bone
• May offer local source for graft harvest
– Greater trochanter, distal femur, proximal or distal tibia,
calcaneus, olecranon, distal radius, proximal humerus
18. AUTOGRAFT HARVEST
• Cancellous harvest technique
– Cortical window made with osteotomes
• Cancellous bone harvested with gouge or currette
– Can be done with trephine instrument
• Circular drills for dowel harvest
• Commercially available trephines or
“harvesters”
• Can be a percutaneus procedure
19. AUTOGRAFT HARVEST
• Cortical
– Fibula common donor
• Avoid distal fibula to protect ankle function
• Preserve head to keep LCL, hamstrings intact
– Iliac crest
• Cortical or tricortical pieces can be harvested in
shape to fill defect
21. – Used in small children where suffiecient graft is
not available from donor site
– In adults where large defects have to be filled
like:
o Periprosthetic long bone fracture
o Revision Total joint surgeries.
o Reconstruction after tumor excision
22. BONE ALLOGRAFTS
• Available in various forms
– Processing methods may vary between
companies / agencies
• Fresh
• Fresh Frozen
• Freeze Dried
23. FRESH BONE ALLOGRAFT
– Limited time to test for immunogenicity or
diseases
– Highly antigenic
– Risk of transmission of diseses
– considerable risk of rejection (about 50%)
– Use limited
24. FRESH FROZEN ALLOGRAFTS
Fresh frozen bone (FFB) is exposed to temperatures
below -70°C
– Less antigenic
– Time to test for diseases
– Strictly regulated by FDA
– Preserves biomechanical properties
• Good for structural grafts
25. FREEZE-DRIED BONE ALLOGRAFTS
• To prepare a freeze-dried bone allograft (FDBA), in
addition to freezing, the donor bone is defatted, the bone
marrow is removed, and it is dehydrated using different
solvents.
– 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
26. DEMINERALIZED FREEZE-DRIED BONE
ALLOGRAFT (DFDBA)
• the HA skeleton of the allograft is removed
using hydrochloric acid, with the aim of
exposing the osteoinductive molecules in
the allograft additionally
28. BONE GRAFT SUBSTITUTES
• They are synthetic or composite materials used to
fill bone defects and promote bone healing.
• Avoid morbidity of autogenous bone graft harvest
• Mechanical properties vary
• Most offer osteoconductive properties
• Some provide osteoinductive properties
29. Bone Graft Substitutes
• Extender for autogenous bone graft
– Large defects
– Multiple level spinal fusion
• Enhancer
– To improve success of autogenous bone graft
• Substitute
– To replace autogenous bone graft
31. BONE GRAFT SUBSTITUTES
• Resorption rates vary widely
– Dependant on composition
• Calcium sulfate - very rapid
• Hydroxyapatite (HA) – very, very slow
• Some products may be combined to optimize
resorption rate
– Also dependant on porosity, geometry
32. • Mechanical properties vary widely
– Dependant on composition
• Calcium phosphate cement has highest compressive
strength
• Cancellous bone compressive strength is relatively
low
• Many substitutes have compressive strengths similar
to cancellous bone
• All designed to be used with internal fixation
33. CALCIUM PHOSPHATE
• Injectable pastes of calcium and phospate
– Norian SRS (Synthes/Stratec)
– Alpha BSM (Etex/Depuy)
– Callos Bone Void Filler (Skeletal Kinetics)
35. • Injectable
• Very high compressive strength once
hardens
• Some studies of its use have allowed
earlier weightbearing and range of
motion
36. How it works ?
– Provides a porous scaffold that resorbs overtime
• Osteoclast cells begin recycling the material at the junction
between bone and cement almost immediately
• Growth factors and antibiotics can be added to the paste in order
to compliment the natural regeneration process
• After healing, all of the cement is replaced with natural new bone
tissue
37. • Osteoconductive void filler
• Low compressive strength – no structural
support
• Rapidly resorbs
• May be used as a autogenous graft extender
- Available from numerous companies
- Osteoset, Calceon 6, Bone Blast, etc.
CALCIUM SULFATE
38. • Pellets
– Pellet injectors
• Bead kits
– Allows addition of
antibiotics
• Injectable
– May be used to augment
screw purchase
Calcium Sulfate
39. TRICALCIUM PHOSPHATE
• Wet compressive strength slightly less than
cancellous bone
• Available as blocks, wedges, and granules
• Numerous tradenames
– Vitoss (Orthovita)
– ChronOS (Synthes)
– Conduit (DePuy)
– Cellplex TCP (Wright Medical)
– Various Theri__ names (Therics)
40. HYDROXYAPATITE
• Produced from marine coral
exoskeletons that are
hydrothermically converted to
hydroxyapatite, the natural
mineral composition of bone
• Interconnected porous structure
closely resembles the porosity
of human cancellous bone
Coralline hydroxyapatite
Cancellous Bone
41. Hydroxyapatite
• Marketed as ProOsteon by Interpore Cross
• Available in various size blocks & granules
• ProOsteon 500
– Very slow resorption
• ProOsteon 500 R
– Only a thin layer of HA
– Faster resorption
42. COLLAGEN BASED MATRICES
• Highly purified Type 1 bovine
dermal fibrillar collagen
• Bone marrow is added to provide
bone forming cells
• Collagraft (Zimmer)
– Collagen / HA / Tricalcium
phosphate
• Healos (Depuy)
– Collagen / HA
43. DEMINERALIZED BONE MATRIX
• Prepared from cadaveric human bone
• Acid extraction of bone leaving
– Collagen
– Noncollagenous proteins
– Bone growth factors
• BMP quantity extremely low and variable
• Sterilized which may decrease the availability of
BMP
44. • Available from multiple vendors in multiple
preparations
– Gel
– Putty
– Strip
– Combination products with cancellous bone
and other bone graft substitute products
Demineralized Bone Matrix
45. • Growth factor activity varies between tissue
banks and between batches
• While they may offer some osteoinductive
potential because of available growth
factors, they mainly act as an
osteoconductive agents
Han B et al. J Orthop Res. 21(4):648-54, 2003.
Blum B, et al. Orthopedics. 27 (1 Suppl): S161 – S165, 2004.
Demineralized Bone Matrix
46. Bone Morphogenetic Proteins
• Produced by recombinant technology
• Two most extensively studied and
commercially available
– BMP-2 (Infuse) Medtronics
– BMP-7 (OP-1) Stryker Biotech
• Used in treatment of non union and open
tibial fracture
48. Graft Incorporation
• Hematoma formation
– Release of cytokines and growth factors
• Inflammation
– Development of fibrovascular tissue
• Vascular ingrowth
– Often extending Haversian canals
49. Primary phase
• Hemorrhage
• Inflammation
• Accumulation of hemopoitic cells including
neutrophills, macrophages, and osteoclasts
• Removal of necrotic bone
50. • Osteoconductive factors released from graft
during resorption and cytokines released
during inflammation
• Recruitment and stimulation of
mesenchymal stem cells to osteogenic cells
• Active bone formation
51. Second phase
• Osteoblasts lines dead trabeculae and lay
down osteoid
• Haemophoitic marrow cells forms new
marrow in transplanted bone
• Remodelling ie woven bone slowly being
transformed into lamellar bone by
coordinated activities of osteoblasts and
osteoclasts.
• Incorporation of grafts
52. Host response to cancellous vs
cortical BG
• In cortical bone graft first osteoclastic
resorption then osteoblastic activity
• Where as in cancellous bone graft bone
formation and resorption occurs
simulaneously called creeping substitution
• Therefore cancellous bone graft
incorporates quickly
• But does not provides immediate structural
support
55. • Partial incorporation of
hydroxyapatite bone
graft substitute
• Biopsy of material
obtained 1 year post-op
Bone Graft Substitute Incorporation
58. ONLAY CORTICAL GRAFT
• Graft is palced subperiosteally across the
fragment without mobilizing the fragmengts
• Cortical graft was suplemented with
cancellous bone
59.
60. Advantages
• Simple to do
• Blood supply of the fragment and the
normal impacting forces of the fracture is
not disturbed
61. Uses
• Malunited, nonunited fractures of shaft of
long bone
• Bridging joints to produce arthrodesis
• Fixation is achieved by internal or external
metallic devices.
62. DUAL ONLAY GRAFT
• Two cortical onlay grafts are placed
opposite each other on the host bone across
the nonunion and are fixed with the same
set of screws
• They grip the fragments like a vise
63.
64. Uses
• To fix non united short osteoporotic fracture
near a joint
• Non union
65. Advantages
• Mechanical fixation is better than fixation
by a single onlay bone graft
• Two grafts add strength and stability
• Grafts from a trough into which cancellous
bone may be packed
• During healing the dual graft prevent
contracting fibrous tissue from
compromising transplanted cancellous
bone.
66. Disadvantages
• Not as strong as metallic fixator devices
• Extremity usually must serve as a donor
site if autogenous graft are used
• The surgery necessary to obtain them has
more risk
67. INLAY GRAFTS
• A slot rectangular defect is created in the
cortex of host bone then a graft of the same
size or slighly smaller is fitted in the defect
• Ocasionally used in arthrodesis, particularly
at the ankle
68. Multiple cancellous chip grafts
• Useful for :
1.Filling defects or cavities resulting from
cysts, tumors etc
2.For establishing bone blocks and for
wedging in osteotomies
69. HEMICYLINDRICAL GRAFTS / MASSIVE
SLIDING GRAFTS
A massive hemicylindrical cortical grafts from
the affected bone is placed across the defect
and supplimented by cancellous iliac bone
Suitable for obliterating large defects of the
tibia and femur
Applicable for resection of bone tumor when
amputation is to be avoided
70.
71. Indications for Bone Graft
• Provide mechanical support
– Metaphyseal impaction
– 27 y.o male with lateral
split/depression tibial
plateau fracture. Note
posterolateral depression.
72. Indications for Bone Graft
• Provide mechanical support
– Metaphyseal impaction
– ORIF with allograft
cancellous bone chips to
fill defect and support
depressed area
– Alternatively could use
any osteoconductive
substitute with similar
compressive strength
73. Indications for Bone Graft
• Provide mechanical support
– Metaphyseal impaction
– 4 months s/p surgery
and the graft is well
incorporated.
74. Indications for Bone Graft
• Provide mechanical support
– Metaphyseal impaction
• Replace bone
– Cortical or segmental
defect
• Stimulate healing
– Atrophic and
Oligotrophic Nonunions
– 26 y.o. woman with
established atrophic
nonunion of the clavicle.
75. Indications for Bone Graft
• Provide mechanical support
– Metaphyseal impaction
• Replace bone
– Cortical or segmental
defect
• Stimulate healing
– Atrophic and
Oligotrophic Nonunions
– Plating with cancellous
iliac crest autograft.
76. Indications for Bone Graft
• Provide mechanical support
– Metaphyseal impaction
• Replace bone
– Cortical or segmental
defect
• Stimulate healing
– Atrophic and
Oligotrophic Nonunions
– 6 months after surgery,
she is healed and
asymptomatic.
77. Indications for Bone Graft
• Provide mechanical support
– Metaphyseal impaction
• Replace bone
– Cortical or segmental
defect
• Stimulate healing
– Nonunions
– Arthrodesis
– Failed subtalar arthrodesis
78. Indications for Bone Graft
• Provide mechanical support
– Metaphyseal impaction
• Replace bone
– Cortical or segmental
defect
• Stimulate healing
– Nonunions
– Arthrodesis
– Repeat fusion with
autogenous iliac crest.
79. Indications for Bone Graft
• Provide mechanical support
– Metaphyseal impaction
• Replace bone
– Cortical or segmental
defect
• Stimulate healing
– Nonunions
– Arthrodesis
– 6 months after surgery,
fused successfully
80. Q.1
You are planning surgery on a
54-year-old female with the
tibial plateau fracture seen in
figures A and B. After
reduction of the joint surface
you plan to fill the void with a
bone-graft substitute to
prevent joint collapse. Which
of the following bone-graft
substitutes disappears most
quickly in vivo? A B
81.
82.
83. Q.2
• Which of the following bone graft material
contains live mesenchymal osteoblastic
precursor cells?
Bone grafts, and bone graft substitutes, are used primarily for three main purposes. One, to provide structural support, such as after elevation of a depressed tibial plateau fracture. Second, to fill a void, such as after excision of a bone cyst in an area that does not demand any structural support. Third, to improve fracture healing. Either by speeding healing or increasing the successful union rate.
Surface cells, which survive with transplantation of either cortical or cancellous grafts, can produce new bone.
Note that cancellous bone, because of its large surface area, has a greater potential for forming new bone than does cortical bone
The most common form of autogenous bone graft is cancellous bone, usually harvested from either anterior or posterior iliac crests, but which also may be harvested locally such as in the proximal tibia or distal radius. Cortical bone strips may be harvested from the inner table of the pelvis. Occasionally a vascularized bone graft may be used, such as a free fibular transfer. Another option for obtaining osteogenic cells is by bone marrow aspirate.
Autogenous bone or autograft is bone transplanted within the same individual
Calcium phosphate products are an injectable paste of calcium and phosphate.
Norian SRS was the first such product available and is marketed by Synthes / Stratec.
Two other calcium phosphate type products are also available in the U.S.
Medical grade calcium sulfate is an osteoconductive void filler. It has low compressive strength so doesn’t offer structural support. Another disadvantage of the product is that it resorbs rather rapidly, perhaps more rapidly then it can be replaced by new bone.
Calcium sulfate products are available both as pellets, bead kits, and injectable preparations. The pellets can be poured into position, but some companies also provide an injector apparatus. The bead kits allow the addition of antibiotics if desired.
Two bone morphogenetic proteins are commercially available. These are BMP-2,marketed by Medtronics, and BMP-7, more commonly known of osteogenic protein 1, produced by Stryker Biotech.
These products are produced by recombinant technology in which large quantities of the material are produced in cell culture.