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Bone Void Fillers : Bone
And Bone substitutes
Dr Sitanshu

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Introduction
• 2nd most common graft
• Gold standard – autogenous cancellous
bone
• Drawbacks – Morbidity
Availability
Operative time

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• Allograft – immune response
disease transfer
impaired osteoconductivity
reduced mechanical property
cost

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• 1st
phase – 4 weeks – mainly from cells of
graft
• 2nd
phase – host cells (endosteal cells,
marrow cells, osteocytes)

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Role of cancellous bone
• Scaffold where cells interact
• Nutrition
• Hematopoiesis, Myelogenesis, Platelet
formation
• Source of pluripotent osteoprogenitor stem
cell
• Local growth factors for differentiation
• Same strength of cortical bone by 6-12
months

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General characteristics of successful
bone graft
Osteogenesis
Osteoinduction
Osteoconduction
Good handling characteristic
Non toxic
Biomechanical property similar to cancellous
bone

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Osteogenesis
Process of bone formation through cellular
osteoblastic activity which depends on the
presence of osteoprogenitor stem cells.

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Osteoinduction
Biologically mediated recruitment and
differentiation of cell types essential for
bone formation.

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Osteoconduction
Apposition of growing bone to three
dimensional surface of a suitable scaffold
provided by the graft.

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Potential use of natural and synthetic
grafts
• Fusion – cervical fusion
lumbar onlay graft
lumbar interbody fusion
arthrodesis
• Bone void filler – collapsed vertebral body
autograft donor site
repair
bony defects

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Autograft - Pros
• Osteogenic
• Osteoinductive
• Osteoconductive
• No disease transmission
• No host rejection

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Autograft - Con
• Viability is compromised
• Quality is not constant
• Second fascial incision

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Minor complications
Superficial infection
Seroma
Hematoma
Temporary sensory loss
Transient pain

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Major complications
• Infection
• Prolonged wound
drainage
• Hernia
• Deep hematoma
• Need for reoperation
• Pain > 6 months
• Profound sensory
loss
• Heterotopic bone
formation
• Vascular injury
• Neurologic injury
• Scars
• Subluxation
• Gait disturbance
• SI destabilization
• Enterocutaneous
fistula
• Pelvic fracture

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• 3cm – distance from donor site and ASIS /
PSIS
• 3cm – maximum distance from dorsal
ilium

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Factors which can’t be avoided
• Increased operative time
• Blood loss
• Donor site – pain
• Cosmetic defect

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Sites
• Iliac crest (Anterior or posterior iliac crest)
• Greater trochanter
• Gerdy's tubercle
• Distal part of the radius
• Distal part of the tibia

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• Autogenous cancellous bone graft is an excellent choice
for nonunions with <5 to 6 cm of bone loss and that
do not require structural integrity from the graft. It can
also be used to fill bone cysts or bone voids after
reduction of depressed articular surfaces such as in a
tibial plateau fracture. Stable internal or external
fixation is also required, to provide the optimum
environment for graft consolidation and successful
fracture-healing.

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Autogenous cortical graft
• Fibula
• Ribs
• Iliac crest

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• With or without vascular pedicle
• Osteoconduction + Osteogenesis
• Non vascularized grafts become weaker in
6 weeks – resorption, revascularization
• Vascularized – stronger – remodelling
similar to normal bone
• But by 6-12 months – no difference
• Fixation required

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• Advantage
• Defects > 5-6cm
• Immediate structural
support
• Disadvantage
• Subjective sense of
weakness and
instability
• Big toe weakness
• Need for reoperation
at donor site

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Osteoconductive matrices
• No osteogenic or osteoinductive property
• Greater source availability
• Elimination of second operative site
• Tricalcium phosphate (alpha, beta)
• Hydroxyapatite
• Injectable calcium phosphate cement

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Graft Material Osteogenesis Osteoinduction Osteoconduction
Autograft 2* 2 2
Allograft 0 1 2
Xenograft 0 0 2
α-TCP 0 0 1
β-TCP (porous) 0 0 2
Hydroxyapatite 0 0 1
Injectable calcium
phosphate cement
(e.g., Norian SRS†) 0 0 1
BMA 3 2 0
β-TCP plus BMA 3 2 2
DBM 0 2 1
Collagen 0 0 2
BMP 0 3 0
Hyaluronic acid 0 0 0
Bioactive glasses 0 0 1 Degradable
polymer 0 0 1
Porous metals 0 0 1

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Allograft
• Surge in popularity – increased availability
donor screening and
tissue processing for safety
new forms has
increased versatility

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• Machine tooling to shape structural
allograft
• Reduction of procurement morbidity
• Potential for immediate structural support
• Reasonable success (60-90%)

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Allograft - ConA
• Results inferior to autograft
• Vary in initial bone quality
• Expensive
• Disease transmission
• Immunogenic reaction

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• Processing – its disadvantage
• Slower resorption
• Not completely replaced by new bone
• Reduced structural integrity
• Poor results in lumbar fusion

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• Donor to donor variation
• Low grade inflammatory reaction

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• Animal studies – correlation between
histocompatibility difference and allograft
failure
• Reaction specific to donor antigen
• CD8+ reaction

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• Fresh frozen
• Retain BMP
• Strong
• Better incorporation
• Immunogenic
• Disease transmission
• Freeze dried
• No BMP
• Weak
• Weaker
• Least immunogenic
• No documented
disease transmission

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Demineralized bone matrix
• Allograft bone that has had the inorganic
mineral removed, leaving behind the
organic collagen matrix
• More osteoinductive properties
• DBM + glycerol carrier – commonly used
• Available data – more as bone graft
extender, not substitute

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• Revascularizes quickly

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Factors affecting DBM product
• Processing
• Time of demineralization
• Final particle size
• Terminal sterilization
• Carrier
• Donor viability

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Carrier for DBM
• Glycerol
• Thermogelling chitosan
• Hyaluronic acid
• Recombinant BMP
• Albumin
• Carboxymethyl cellulose

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Disadvantage
• Difficulty in handling
• Tendency to migrate from graft site
• Lack of stability
• Transmit disease

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Xenograft
• From animals
• Impractical for clinical use on a wide scale
• Removal of protein and fat – processing
• Removes osteoinductive proteins
• Kiel bone, Oswestry, Bio Oss

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Ceramics
• Stable compounds of metals with oxygen
or other anions
• Non injectable ceramics – according to
resorbing power
• Injectable ceramics

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Non injectable ceramics
• Osteoconductive
• Hydroxyapatite, Tricalcium phosphate,
Calcium sulphate dihydrate
• High quality synthetic material with no
biologic hazards

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• Alternative or as an addition to either
cancellous autograft or allograft or as a
cancellous bone void filler or bone graft
extender or in sites where compression is
the dominant mode of mechanical loading
• Safe and effective substitute for iliac graft
autograft
• Cost

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Rapidly resorbing ceramics
• Tricalcium phosphate (alpha 1200
degrees, beta at 800 degrees) – 39% Ca,
20% P
• Calcium sulfate

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• Calcium phosphate – calcium phosphate
rich microenvironments that stimulate
osteoclastic resorption and then
osteoblastic new bone formation, resulting
in new bone formation
• Pore size - less porous formulations
resorb before complete bone ingrowth

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• Calcium sulfate - Osteoconductive but its
rapid resorption rate creates doubt about
its ability to maintain a three-dimensional
framework to support Osteogenesis

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Intermediate resorbing ceramic
• Beta tricalcium phosphate - In the process
of being resorbed, it can enrich the local
environment with osteogenic substrates
that, in turn, can be used by activated
osteoblasts
• Broad range of pore size (<1µm to
1000µm)
• Sponge-like interconnected microporosity
endowed with excellent wicking and
hydrophilic properties

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Slow resorbing ceramic
• Hydroxyapatite
• Bone incorporation – pore size and pore
interconnectivity
• Drawback - slow resorption, brittle

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Injectable ceramics
• Calcium phosphate cement - paste of
inorganic calcium and phosphate that
hardens in situ with a low exothermic
temperature
• Slowly transforms into bone over 3 to 4
years
• Adjunct to fixation in both femoral neck
and intertrochanteric hip fractures

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• Drawbacks – 1. slow resorption
2. low porosity
3. high cost
4. extravasation
5. intra articular extension
6. increased washout
7. low shear resistance

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Collagen
• Animal-derived collagen with synthetic
calcium phosphate
• Putty-like consistency
• Can be used as bone graft extenders to
increase the volume of bone graft into a
defect when a sufficient volume of
autograft is not readily available

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Non biologic Osteoconductive
substrates
1. absolute control of the final structure
2. no immunogenicity
3. excellent biocompatibility
Degradable polymers - polylactides
Bioactive glasses
Porous metals - tantalum

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Composite graft
• Any combination of materials that includes
both an osteoconductive matrix and an
osteogenic or osteoinductive material
1.Bone marrow aspirate
2.Osteoblastic progenitor stem cell
3.Blood
4.Platelet rich plasma
5.Growth factors

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Bone marrow aspirate
background
• Osteoblast progenitor cells – 1.periosteum
of long bones 2.the peritrabecular
connective tissue 3.the bone marrow
• All the critical cellular components that
contribute to bone growth present
• Fibroblast, undifferentiated cells
• Animal research suggests that precursor
cells in bone marrow proliferate and
differentiate after transplantation

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• Availability and the relative safety of its
harvest
• Harvested by aspiration from patients, with
limited dilution by peripheral blood
• Concentration
• Culture

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Bone composite
• Used successfully to stimulate healing in
tibial fractures
• Osteogenic potential was maintained as
the cells were expanded in culture
• Facilitated greater bone formation and
fusion success rates
• Xenograft bone and other bone
substitutes could be rendered osteogenic

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Synthetic composite
• Addition of BMA was essential for
tricalcium phosphate and hydroxyapatite
to achieve results comparable to those
obtained with cancellous bone at 24
weeks
• β-TCP/BMA composite may be superior
even to autograft, which suffers from
anoxic cell death in the center of the graft
because of the absence of vascularization

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BMP and synthetic composite
• BMP 2, BMP 7 (rhOP 1)
• Carrier to maintain optimum regional
concentration
• Hydroxyapatite
• DBM
• Hyaluronic acid
• Collagen