BONE

GRAFTING
DEFINITION
• USFDA definition :
bone grafting is defined as a
material that is intended to fill, augment or
reconstruct the bony defects
• Bone grafting is the surgical procedure
in which new bone (bone graft) or a
replacement material (graft substitute),
is placed into bone fractures or bone
defects to aid in healing
EPIDEMIOLOGY
• Of the more than 3 million
musculoskeletal procedures done
annually in the United States, about
half involve bone grafting with either
an autograft or an allograft.
• Worldwide, autografts or allografts are
used in approximately 2.2 million
orthopaedic procedures annually.
• Surgeons transplant bone at least 10
times more often than they do any
other transplantable organ.
HISTORY
• The first recorded bone implant was
performed in 1668 by Job van
Meekeren performed the first bone
graft using a canine xenograft to repair
a cranial defect .
• MacEwen 1881- used fresh bone
allografts obtained as surgical
residues from a live donor to
reconstruct the humeral shaft of a
child with osteomyelitis
• Duhamel 1743- periosteum has a
pivotal role in osteogenesis
• Leopold ollier 1861 –osteogenetic
capability of periosteum to autologous
and homologous grafts
• Lexer 1908- reported on the implantation of 34
allograft hemi- and total joints procured from
freshly amputated limbs and cadavers.
• Herndon and Chase, and Curtiss and co-workers
1959- indicated that freezing reduces the
immunogenicity of allograft
• Ottolenghi, Volkov and Parrish in the 1960s and
1970s separately reported large series of
patients in whom frozen allografts were used
• Dr George Hyatt, the first Director of the Navy
Tissue Bank in Bethesda, USA. In 1949, he began
the banking of surplus bone from surgical
procedures, in a small freezer
• Phemister introduced the term creeping
substitution. He believed that transplanted bone
was invaded by vascular granulation tissue,
causing the old bone to be resorbed and
subsequently replaced by the host with new
bone
• Abbott and associates have shown that, in
addition, surface cells in the bone graft survive
and participate in new bone formation
• Ray and Sabet and Arora and Laskin also
confirmed the fact that superficial cells in the
bone graft probably survive transplantation and
contribute to new bone formation
TYPES
Based on source:
Autograft –Obtained from same individual

Isograft/ syngraft –obtained from identical twin

Allograft- obtained from different person from

same species Xenograft/ heterograft- obtained

• Based on
contents:
• Cortical
• Cortico-
cancellous
• Cancellous
• Based on
Vascularity:
• Vascular
• Non-Vascular
• Based on method of
preservation:
• Fresh
• Frozen
• Freeze dried
• Demineralized
LAURENCIN ET AL CLASSIFICATION OF
GRAFTS AND GRAFT SUBSTITUTES

• A. Harvested bone grafts and graft

substitutes
• B. Growth factor-based bone graft
substitutes
• C. Cell-based bone graft substitutes
• D. Ceramic-based bone graft
substitutes
• E. Polymer-based bone graft
substitutes
• F. Miscellaneous
HARVESTED BONE GRAFTS AND
GRAFT SUBSTITUTES

• Bone grafts, endogenous or exogenous,

are often essential to provide support, fill
voids, and enhance biologic repair of
skeletal defects due to traumatic or non-
traumatic origin.
• Allograft bone substitutes used alone or in
combination with other materials
GROWTH FACTOR-BASED BONE GRAFT
SUBSTITUTES

• Natural and recombinant growth factors used

alone or in combination with other materials

• Ex transforming growth factor-beta

: (TGF-beta) platelet-derived growth
factor (PDGF) fibroblast growth
factor (FGF)
bone morphogenetic protein (BMP).
CELL-BASED BONE GRAFT
SUBSTITUTES

• Use cells to generate new tissue alone or

are seeded onto a support matrix
• e.g., mesenchymal stem cells
CERAMIC-BASED BONE GRAFT
SUBSTITUTES
• Include calcium phosphate, calcium sulfate, and
bioglass
• Used alone or in combination

• e.g., OsteoGraf [DENTSPLY Friadent CeraMed,

Lakewood, Colo] Norian SRS [Synthes, Inc, West
Chester, Pa]
ProOsteon [Interpore Cross International, Irvine,
Calif] Osteoset [Wright Medical Technology, Inc,
POLYMER-BASED BONE GRAFT
SUBSTITUTES
• Degradable and nondegradable polymers
• Are used alone or in combination with other
materials
• e.g., Cortoss [Orthovita, Inc, Malvern, Pa]
open porosity polylactic acid polymer
[OPLA] Immix [Osteobiologics, Inc,
San Antonio, Tex]
MISCELLANE
OUS
• Various unconventional marine biomaterials
are also in use as bone graft substitute
which includes coral, chitosan, sponge
skeleton etc.
Bone grafts and their substitutes can also be
divided into
• Osteoinductive agents

• Osteoconductive agents

• Osteogenic agents
Osteoinductive agents-
• Generally proteins
• Induce differentiation of undifferentiated
stem cells to osteogenic cells or induce
stem cells to proliferate
Osteoconductive agents
• Provides microscopic and macroscopic
scaffolding for inward migration of cellular
elements involved in bone formation
• e.g., mesenchymal cells, osteoblasts,
osteoclasts, and vasculature
• Osteogenetic agents –
• osteogenesis refers to bone formation
with no indication of cellular origin new
bone may originate from live cells in the
graft or cells of host origin.
• The ideal bone graft or bone graft
substitute should provide three essential
elements:
• Osteoconductive matrix
• Osteoinductive properties or factors
• Osteogenic cells.
• Osteoconductivity- defined as the process of
infiltration of capillaries, perivascular tissue, and
osteoprogenitor cells from the host bed into the
transplant.
• Osteoinduction is the stimulation of a tissue to
produce osteogenic elements. This process is
controlled primarily by growth factors such as bone
morphogenetic proteins (BMPs) that are capable of
inducing differentiation of mesenchymal cells into
cartilage and boneproducing cells.
• Osteogenetic cells are mesenchymal-type cells, and
they can be
summoned from host or graft bone marrow
The autogenous cancellous bone graft satisfies all
three categories most completely.
• Hydroxyapatite and collagen serve as the
osteoconductive framework
• stromal cells lining the microcavities possess the
necessary
osteogenic potential
• the endogenous family of growth factors within
the bone and adjacent hematoma fully induce
both the regenerative and augmentation
processes.
 INDICATIO
NS
1.To fill cavities or defects resulting from cysts, tumors, or
other causes
2.To bridge joints and thereby provide arthrodesis
3.To bridge major defects or establish the continuity of a
long bone
4.To provide bone blocks to limit joint motion (arthrorisis)
5.To establish union in a pseudarthrosis
6.To promote union or fill defects in delayed union,
malunion, fresh fractures, or osteotomies
7.To plastical arthrosis of acetabulum for Congenital
Dislocation of the Hip and Perthes disease
STAGES OF BONE GRAFT
INCORPORATION
• 5 stages
Inflammation stage ( bone resorption and chemotaxis by necrotic tissue
and inflammation )

Osteoblast differentiation ( form cells in graft or marrow precursors )

Osteoinduction ( support and growth of bone

cells ) Osteoconduction ( scaffold to guide cells for

bone formation ) Remodeling ( graft modification to

the innate bone structure )

HARVESTED BONE GRAFTS AND GRAFT
SUBSTITUTES
• Autogenous bone grafting:
Autogenous bone grafts are considered as the gold
standard for bone replacement mainly because
They offer minimum immunological rejection
Complete histocompatibility and
Provide the best osteoconductive, osteogenic and
osteoinductive properties Disadvantages :
• Autogenous grafts are in limited supply
• Associated with high rates of donor site morbidity
• Increased inpatient stay and
• Higher associated costs
Cancellous bone graft
Predominantly of soft spongy bone
Contains high number of living bone
cells
Mainly acts as a filter to obliterate
cavities
Poorly resists compression or bending
force
More biological support to healing
Incorporates faster
Can be used in places that have
potential for being infection
Cortical bone graft
Predominantly of hard cortical bone
Contains more of bone matrix and
less cells
Mainly acts as structural support
Good compressive strength and
provide
tensile strength also
Less biological support to healing
Slow incorporation
Should not be used at infected sites
REMOVAL OF TIBIAL
GRAFT
• Make a slightly curved longitudinal incision over the anteromedial
surface of the tibia,
• placing it so as to prevent a painful scar over the crest
• Complication
• The most feared complication of tibial bone graft is the risk of fracture.
• O’Keeffe et al reported one nondisplaced fracture of the tibial eminence
• Thor and Van Damme and Merkx reported fractures of the tibial
metaphysis in the early
• postoperative period
• Impact activities and sports be avoided for 4-6 weeks postoperatively
REMOVAL OF FIBULAR
GRAFT
In the removal of a fibular graft three points should receive
consideration:
• The peroneal nerve must not be damaged
• The distal fourth of the bone must be left to maintain a
stable ankle
• The peroneal muscles should not be cut.

The middle one third of the fibula also can be used as a

vascularized free autograft based on the peroneal artery and
vein pedicle using microvascular technique
• Complications :
• Peroneal nerve
injury
• Knee instability
• Ankle instability
• Muscle
weakness
REMOVAL OF ILIAC BONE
GRAFT
• Ideal source because :
• Subcutaneous
• Natural curvature
• Ample cencellous bone
• Cortical bone of variable thickness
• No residual disability
• Minimal risk
• In general :
• Cancellous grafts incorporate with the host bone more
rapidly than do cortical grafts.
• At least 2 cm of subchondral bone must remain to avoid
collapse of the articular surface.
 POSTERIOR ILIAC
•
GRAFTS
Best source of Cancellous bone
• Vertical incision or curvilinear incision
• Transverse incision –injury to gluteal nerves,
dehiscence, painful
 ANTERIOR ILIAC
GRAFTS
• Large grafts of cancellous and
corticocancellous bone can be
harvested
• The middle ilium is paper thin, but the
anterior column just above the
acetabulum is quite thick.
COMPLICATIONS OF ILIAC BONE
GRAFT
• Pain
• Wound healing
complications
• Nerve damage
• Hernia
• Pelvic fracture
• Hematoma
• Vascular injury
• SI joint instability
• Ureteral injury
 INDICATIONS FOR VARIOUS
TECHNIQUES
• Single Onlay Cortical Grafts
• Used in :
• fresh, malunited, and ununited fractures
and after osteotomies.
• bridging joints to produce arthrodesis
• for fixation (unusual)
• Dual Onlay Grafts
• they grip the small fragment like forceps
• useful when :
• treating difficult and unusual nonunions or for the
bridging of massive defects.
• Advantages :
• Better mechanical fixation
• form a trough into which cancellous bone may be packed
• prevent contracting fibrous tissue from compromising
transplanted
cancellous bone.
• The disadvantages of dual grafts:
• They are not as strong as metallic fixation
devices
• They are not as osteogenic as autogenous
iliac grafts,
• The surgery necessary to obtain them has
more risk.
 BICORTICAL
•
GRAFTS
for spinal fusion or for replacement of major bone defects in
metaphyseal regions
The advantages of dual grafts:
• Mechanical fixation is better than fixation by a single
onlay bone graft
• The two grafts add strength and stability
• The grafts form a trough into which cancellous
bone may be packed
• During healing the dual grafts, unlike a single
graft, prevent contracting fibrous tissue from
compromising transplanted cancellous bone
INLAY
GRAFTS
• Replacedby onlay grafting
• Occasionally done in arthrodesis
of ankle
MEDULLARY
GRAFTS.
• Were tried early in the development of bone grafting
techniques for nonunion of the diaphyseal fractures.
• Fixation was insecure, and healing was rarely
satisfactory.
• This graft interferes with endosteal circulation and
consequently can interfere with healing
• because they are in the central axis of the bone,
they resorb rather than incorporate.
• The only possible use for a medullary graft is in the
metacarpals and the metatarsals, where the small
size of the bone enhances incorporation.
OSTEOPERIOSTEAL
GRAFTS
• The periosteum is harvested with chips of
cortical bone.
• These grafts have not been proven to be
superior to onlay cancellous bone grafting
• More difficult than cancellous bone to harvest
• Greater morbidity
PEDICLE
GRAFTS
• Pedicle grafts may be local or moved from a
remote site using microvascular surgical
techniques.
• In local muscle-pedicle bone grafts, an attempt is
made to preserve the viability of the graft by
maintaining muscle and ligament attachments
carrying blood supply to the bone or, in the case of
diaphyseal bone, by maintaining the nutrient artery.
• Two examples are the transfer of the anterior iliac
crest on the muscle attachments of the sartorius
and rectus femoris for use in the Davis type of hip
fusion
• The transfer of the posterior portion of the greater
MULTIPLE CANCELLOUS CHIP
GRAFTS
• Widely used for grafting.
• Segments of cancellous bone are the best
osteogenic material available.
• They are particularly useful for filling cavities or
defects resulting from cysts, tumors, or other
causes, for establishing bone blocks, and for
wedging in osteotomies.
• If some rigidity and strength are desired, the
cortical elements may be retained.
• In most bone-grafting procedures that use cortical
bone or metallic devices for fixation,
supplementary cancellous bone chips or strips
PEG AND DOWEL
GRAFTS
• Dowel grafts were developed for the grafting of
nonunions in anatomic areas, such as the
scaphoid and femoral neck, where onlay bone
impractical.
grafting was
• Free microvascularized fibula grafts are more
commonly used
today
FIBULAR BONE GAFTING FOR DEFECT
OF TIBIA CAUSE OSTEOMYELITIS
• The rules of bone grafting for long defects in the diaphyseal
portion of extremity
due to osteomyelitis are:
• General status is stable: ESR: < 10 mm/h; CRP: < 10 mg/L ;
WBC: <
• 10.000; Neutrophil: < 60%;
• Local extremity with bone defect: no swelling, no hottemperature,
no pain, and
no pus fistula for at least 3 months
• Remove sclerosis bone until bone bleeding
• Solid fixation of bone graft into bone bed by Kirschner wire or
plate and screw and plaste cast
• The Kirschner wire will be removed when clear clinical and
radiographic evidence of solid union were apparent (mean
BONE MARROW
ASPIRATE
• Used to stimulate bone formation in skeletal defects
and nonunion through cytokines and growth factors
secreted by the transplanted cells
• The main advantage of this technique is that it can
be performed percutaneously, without almost any
patient morbidity.
• Centrifugation of aspirated bone marrow at 400
times gravity for ten minutes separates the marrow
cells from plasma and preserves the osteogenic
potential of the cells, decreasing the volume of
material injected.
• Proliferation and differentiation of stem cells may be
increased by adding them into growth factors or by
• Autologous bone marrow mixed with 10 mg of
demineralized bone matrix has been successfully
used to fill bone defects as demineralized bone
matrix is an excellent carrier because of its
osteoinductive as well as osteoconductive
properties.

• Injection of autologous bone marrow, with or

without a carrier, has been used to treat nonunion
and delayed union of several bones.
ALLOGENIC BONE
GRAFTS
• The limitations associated with the procurement of
autograft for bone grafting can be overcome by the
use of allografts
• has both osteoinductive (they release bone
morphogenic proteins that act on bone cells) and
osteoconductive properties, but lack osteogenic
properties because of the absence of viable cells
Advantages
 Ready availability in various shapes and sizes
 Avoidance of the need to sacrifice host structures
 No donor site morbidity
INDICATIONS FOR
ALLOGRAFTS
• Packing cavities left after benign tumor excision or
traumatic defects.
• Wedges or blocks for arthrodesis of spine or
osteotomy.
• Packing a cage for spinal fusion.
• Partial cortical defects, post-traumatic or after
tumor excision.
• Full segment defects like those after tumor
excision.
• Osteoarticular segment replacement after tumor
excision.
Complicatio
ns :
• Infection
• Nonunion
• Fracture
• Allogenic bone is available in many
forms:
• Demineralized bone matrix
• Morselized and cancellous chips
• Corticocancellous and cortical
grafts
• Osteochondral and whole-bone
segments.
DEMINERALIZED BONE MATRIX
(DBM):
• Advantages:
• Acts as suitable carrier for autologous bone
marrow.
• It does not evoke any appreciable local foreign
body immunogenic reaction as antigenic surface
structure of bone is destroyed during
demineralization
Disadvantages:
• Because it is an allergenic material, there is the
potential to transmit human immunodeficiency
virus (HIV).
• Another possible limitation of demineralized bone
matrix is that different batches may have different
potencies because of the wide variety of donors
used to supply the graft
GROWTH FACTOR-BASED BONE GRAFT
SUBSTITUTES
• Fracture healing, like all tissue healing processes
that result from injury and acute inflammation, is
orchestrated by chemical mediators.
• The process is both complex and redundant, with
several protein factors inducing and inhibiting
cell differentiation and new bone
growthoccurred.
• All mediators utilize membrane receptors and act
through cell signaling pathways that induce either
cell proliferation and differentiation in the case of
osteoprogenitor CFU-Fs or induce upregulation of
expression of bone components such as collagen
from differentiated osteoblasts
The chemical mediators identified to date are
• Members of the transforming growth factor-beta
(TGF-) superfamily that include bone
morphogenetic proteins (excluding BMP-1) and the
BMP subclass of growth/differentiating factors 1–10,
inhibins, activins, Vg-related genes, nodal-related
genes, and glial-derived neurotropic factor
• Acidic and basic fibroblast growth factors (FGF)
• Platelet- derived growth factor (PDGF)
• Insulin-type growth factors (IGFs).
BONE MORPHOGENETIC
PROTEINS
• Because of their role in osteoblast
differentiation, growth, and activation, a
multitude of preclinical research has focused
on the relevance of recombinant versions of
these growth factors
• BMP undergoes cleavage and glycosylation forms active BMP

• bind types I and II serine/threonine kinase receptors on osteoprogenitor

cell membrane

• type II BMP receptors activate type I receptors, which are solely able to
initiate an
intracellular signaling reaction

• This complex signaling cascade results in activated proteins, known as

SMADs, which bind to DNA
• transcriptional activation of the osteoblast-specific factor-2/core-binding
factor-1 gene,
either directly or indirectly

• resulting protein is a potent transcription activator of osteocalcin, which

is the defining molecular marker of differentiated osteoblasts
• Kirker-Head and coworkers evaluated the long-
term healing of bone using rhBMP-2 in adult sheep
. By 12 mo all the defects were structurally intact
and were rigidly healed
• Cook and his coworkers have utilized BMP-7 to
heal large segmental defects in rabbits, dogs,
and primates
• In a systematic review and analysis of randomized
controlled trials by Garrison et al. (2007), the clinical
effectiveness of BMP for the treatment of spinal
fusions and the healing of fractures was compared
with the current standards of care.
• This review found that there was evidence that
FIBROBLAST GROWTH
FACTORS
• Fibroblast growth factors (FGFs) compose
another family of growth factors evolved in
wound healingand repair.
• Specifically, they act on both stem and
differentiated cells, causing changes in
migration, proliferation, further differentiation,
morphology, and function
• There are nine known members of this protein
family, all of which share 30–50% sequence
homology.
• FGF-1 and FGF-2, also termed acidic FGF (aFGF)
and basic FGF (bFGF), respectively (named for
their differing isoelectric points), are the prototypic
• Four distinct FGF receptors have been identified.
They all exhibit dimerization and tyrosine kinase
activity upon binding their respective ligand
• The dimerized receptor/ligand complexs are
clustered together and endocytosed, where
individual phosphotyrosine residues act as highly
selective binding sites for specificed intracellular
proteins that go on to modulate DNA transcription
• Human recombinant forms of FGF applied
exogenously to fractures demonstrated increased
differentiation among mesenchymal stem cells into
chondroprogenitor cells, increased callus volume
and density
• Radomsky et al. have experimented extensively with
hyaluronate gel as a potential carrier.
• This viscous gel formulation is used in direct
percutaneous injection into fresh fractures,
effectively releasing FGF in a slow- release manner.
• These studies demonstrate increased callus size,
periosteal reaction, vascularity, and cellularity
• Single local injections and continuous slow infusions of FGF
have also demonstrated increased cytokine-induced bone
formation and accelerated fracture recovery when compared
to nontreated control
• low doses (15 ng per implant) of bFGF have been found to
induce the number of chondrocytes and bone formation,
whereas high doses (1900 ng per implant) greatly inhibit
cartilage and bone formation.
• It is known that FGF can stimulate the differentiation of
osteoclasts from bone marrow stem cells through FGF-
stimulated expression of prostaglandins.
• However, it is not known if high doses of FGF inhibit collagen
and bone
synthesis through increased prostaglandin expression.
TRANSFORMING GROWTH
FACTOR –BETA
• Data to support the concept that exogenous TGF-
beta can
stimulate bone repair is substantial, but the overall
osteoinductive capacity of TGF- is weak compared
to the bone morphogenetic proteins
• TGF- may potentiate the osteoinductive activities of
the BMPs,
and this may be an important role for this factor
• Three isoforms of TGF- exist in mammalian species,
although it appears all three act on similar receptors.
The most concentrated isoform is TGF- type 1,
which is stored in platelet - granules.
• TGF- type-1’s critical role in soft tissue and fracture repair
PLATELET- DERIVED GROWTH
FACTOR
• Platelet-derived growth factor (PDGF) has been shown to
have stimulatory
effects on bone and cartilage cells proliferation.
• However, its role in fracture healing is not clearly understood.
• The active receptors of PDGF are composed of two
separate subunits ( alpha and beta )
• PDGF –alpha chain was found to be expressed by many cell
types over a
prolonged period during fracture healing.
• These cells include the endothelial and mesenchymal cells,
and granulation tissue in the osteoblast, chondroblast sites,
osteoclasts later during fracture healing.
• In contrast, platelet-derived growth factor-beta change to gene
expression was more restricted, being directed principally in
osteoclasts at the stage of bone formation
• Because of PDGF’s increasingly important role in bone
regeneration and remodeling, a group has begun
experimenting with platelet-rich plasma (PRP) and
platelet-poor plasma (PPP), both rich in PDGF, TGF-
, and TGF-, as possible bone graft materials
• Synthetic graft materials treated with PRP and PPP
extracts demonstrated a greater trabecular bone
density than did bone control grafts without the
extracts through the first
 CELL-BASED BONE GRAFT
SUBSTITUTES:
stem cell
 Stem cell is an ‘immature’ or undifferentiated cell which is capable of producing any
identical daughter cells
 The main sources of stem cells include somatic (Adult) and
embryonic stem cells.
 Somatic stem cells include haematopoietic stem cells, bone
marrow stromal (Mesenchymal) stem cells (MSC) neural stem
cells dermal (Keratinocytes) stem cells
 The best options are those derived from the bone marrow which
yields two types
- the haematopoietic stem cells which gives rise to the entire
blood cell
lineage and
- the mesenchymal stem cells from which are derived various
Success has been restricted by
• Problems of dosage
• Lack of full activity of recombinant factors
and
• The inability to sustain the presence of the
factor for an appropriate length of time
Collagen
 Collagen as an osteoinductive material used in
combination with osteoconductive carriers like
hydroxyapatite or tricalcium phosphate
 Chapman et al conducted a prospective, randomized
comparison of autologous iliac crest bone graft and calcium-
collagen graft material in the treatment of acute long-bone
fractures with both bone-grafting and internal or external
fixation.
 The authors observed no differences between the two groups
with regard to the union rate or functional measures, and they
concluded that calcium- collagen graft material with
autologous bone marrow can be used instead of autologous
bone graft for patients who have an acute traumatic defect of a
long bone
• There is no scientific proof that calcium-collagen
graft materials can effectively substitute for
autologous bone graft to stimulate healing of
nonunion
• It is not recommended to fill metaphyseal bone
defects resulting from articular fractures as it does
not offer structural support
Gene therapy :
 Gene therapy involves the transfer of genetic
information to cells
 The gene therapy used for gene induction is short-
term and as regional therapy.
 The gene can be introduced directly to specific
anatomic site (in-vivo technique) or
 specific cells can be harvested from the patient,
expanded, genetically manipulated n tissue
culture and then reimplanted (ex-vivo technique).
• Viral and non-viral vectors can be used for the
delivery of genetic materials into cells.
• Non-viral gene transfer systems such as liposomes,
naked DNA are usually easier to produce and have
a lower toxicity and immunogenicity, but the
efficiency of their gene delivery is impeded by a
blow rate of infection
• Recently, viral gene vectors, including retrovirus,
adenovirus, adeno-associated virus and herpes
virus are more efficient method of gene transfer
• Tomita et al first reported successful delivery of
genes into the articular cartilage using a
haemagglutinating virus (HVJ; sendai virus)
liposome suspension containing the SV40 large T
antigen (SVT) gene which was injected intra-
articularly into the knees of rats.
• biological effect of an effective growth factor in
cartilage healing was studied using rabbit
mesenchymal stem cells transduced with retroviral
vectors encoded for the gene of bone
morphogenetic protein-7, seeded on polymer
scaffold grafts implanted into osteochondral defects
in rabbit knees
CERAMIC-BASED BONE GRAFT
SUBSTITUTES
• Among different ceramic based graft
substitute materials, calcium phosphate
based ceramics such as hydroxyapatite (HA),
β-tricalcium phosphate (β-TCP) and bioactive
glass are used quite substantially for long
time
CALCIUM HYDROXYAPATITE
(HAP)
• Hydroxyapatite is a biocompatible ceramic
produced through a high-temperature reaction and
is highly crystalline form of calcium phosphate.
• The nominal composition of this mixture is Ca10
(PO4)6 (OH) 2 with a calcium-to-phosphate atomic
ratio of 1.67.
• The most unique property of this material is
chemical similarity with the mineralized phase of
bone; this similarity accounts for their
osteoconductive potential and excellent
biocompatibility
• During recent years, there have been efforts in
developing doped bioceramics materials to
enhance their mechanical and biological
properties as well as cytocompatibility for use in
tissue engineering applications.
• Hydroxyapatite (HA) as a synthetic material, usually
used as coating for dental and orthopedic implants,
are known for its good cytocompatibility properties,
but is limited in use due to its moderate to low
solubility within the body and mechanical properties
that differ from surrounding tissue and bone.
• Doped HA with manganese and/or zinc as bone
substitute have been tried and resulted in faster
• Plasma spray HA coating has been used on
metallic femoral stem and cup as a means of
fixation in order to avoid complications related to
the use of PMMA.
• Hydroxyapatite-coated pins enhance pin fixation
regardless of bone type and loading conditions and
reduces the rate of infection and loosening during
external fixation
Tri-calcium phosphate (TCP)
 Like hydroxyapatite, TCP is bioabsorbable and
biocompatible.
 The chemical composition and crystallinity of the
material are similar to those of the mineral phase
of bone.
 It exists in either α or β-crystalline forms.
 The rate of biodegradation is higher when
compared with HA
 Recombinant human bone morphogenetic protein
(rhBMP)-2 with beta-TCP is a promising
composite having osteogenicity and efficient
enough for repairing large bone defects
Bio-active glass
• Bio-active glass ceramics (Bioglass) were first
developed by Hench et al
• It is biocompatible, osteoconductive and bonds to
bone without an intervening fibrous connective
tissue interface.
• This material has been widely used for filling
bone defects alone and in combination with
autogenous and allogenic cancellous bone
graft.
• Bioglass is composed mainly of silica, sodium
oxide, calcium oxide and phosphates.
Bioactive glasses have been clinically used for
• As filling material in benign tumour surgery
• For reconstruction of defects in facial bones
• For treatment of periodontal bone defects
• In repairing orbital floor fractures
• In lumbar fusion and
• For reconstruction of the iliac crest defect after
bone graft harvesting
Calcium phosphate cement
 The paste or injectable calcium phosphates
cement offers the advantage of being freely
mouldable and adaptable to bone defects
 The combination of high biocompatibility, easy-to-
shape characteristic, and the capacity to self-setting
under ambient conditions makes it an asset in the
repair of hard tissue defects.
 Based on its flow behavior before setting of slurry,
has been used as an injectable biomaterial for
bone replacement, especially in percutaneous
vertebroplasty and
kyphoplasty
Calcium Sulfate:
• Calcium sulfate graft material with a patented crystalline
structure described as an alphahemihydrate acts primarily as
osteoconductive bone-void filler that completely resorbs as
newly formed bone remodels and restores anatomic features
and structural properties.
• Potential application of calcium sulfate graft material includes
the filling of cysts, bone cavities, benign bone lesions and
segmental bone defects; expansion of grafts used for spinal
fusion; and filling of bone-graft harvest sites.
• It is biocompatible, bioactive and resorbable after 12 wk
• Significant loss of its mechanical properties occurs upon its
degradation; therefore, it is a questionable choice for load-
bearing applications.
POLYMER-BASED BONE GRAFT
SUBSTITUTES
• Two types – Natural
- Synthetic
Each divided into degradable and nondegradable
Eg : Healos (DePuy Orthopaedics, Inc, Warsaw, Ind) is
a natural polymer-based product, a polymer-ceramic
composite consisting of collagen fibers coated with
hydroxyapatite and indicated for spinal fusions
MISCELLANEOUS
Coral :
 Chiroff et al198 first observed that corals from marine
invertebrates have skeletons with a structure similar to both
cortical and cancellous bone, with interconnecting porosity.
 Coralline hydroxyapatite is processed by a hydrothermal
exchange method that converts the coral calcium phosphate
to crystalline hydroxyapatite with pore diameters between
200 and 500 μmand in a structure very similar to that of
human trabecular bone
 Bucholz et al reported that the clinical performance of
autologous cancellous bone graft and coralline hydroxyapatite
are similar during filling of bone voids resulting from articular
surface depression in tibial plateau fractures.
 More recently, coralline hydroxyapatite has been used as a
carrier for some bone derived growth factors.
• Coralline hydroxyapatite granules or blocks of
various size, depending on the size of the defect
can be used to fill metaphyseal defects after
reduction of depressed articular segments.
• Coralline hydroxyapatite bone graft substitute
appears to be a clinically effective material for use
in foot procedures although the slow resorption is
a concerning characteristic of the graft material
without any adverse effect.
• Another contraindication to the use of this material
is a joint surface defect that would allow the
grafting material to migrate into the joint.
• Chitosan and Sponge skeleton:
• The abundance and structural diversity of natural
marine sponge skeletons and their potential as
multifunctional, cell conductive and inductive
frameworks along with collagenous composition
of the fiber indicate a promising new source of
scaffold for tissue regeneration
• Chitosan, a natural product derived from the
polysaccharide chitin (Aminopolysaccharide;
combination of sugar and protein), an abundantly
available natural biopolymer found in the exo-
skeletons of crustacean like shrimp, crabs, lobster
and other shellfish would be an effective material to
• In an experimental study, natural
hydroxyapatite/chitosan composite were evaluated
in reconstruction of bone defects and observed that
this composite has good biocompatibility and
osteoconduction
BONE BANKING
Bone banking in INDIA:
• While bone banking is well developed and regulated
in the USA and Europe, in India it is still largely
arbitrary.
• The most commonly used methods for banking
bone are freezing between -20°C and -80°C or
Defatting followed by freeze-drying and
sterilization by ethylene oxide.
BONE DONATION:
• The source of bone for transplantation may be
either cadavers or live donors.
• In the case of cadaver donors, tissues must be
retrieved as soon after death Usually, procurement
of musculoskeletal and osteoarticular tissues
should commence
• within 15 hours after death
• Tissues from live donors are obtained as
surgical residues consequent to surgical
procedures
• ethical considerations form an essential component of bone
banking.
• When bone is removed during a surgical procedure for
therapeutic purposes other than to obtain tissue (e.g. joint
replacement surgery, traumatic amputations) the donor must be
informed of the donation, the possible use of the bone and the
requirement of a blood sample for thedetection of HIV 1 and 2,
Hepatitis and syphilis.
• In the case of a deceased donor the legal next-of-kin must
be similarly informed.
• Informed written consent of the donor or the legal next-of-kin in
the case of a cadaver donor, with respect to the above, must
accompany every bone donation
• DONOR SELECTION:
• The first step in donor selection is the screening of
potential donors for infectious diseases, or
diseases of unknown origin that could prove
infectious.
• Information regarding the donor’s age and medical
history is
obtained.
• In the case of cadaveric donors, physical
examination, behavioral history, probable
cause of death and autopsy findings, if
performed, is reviewed
• EXCLUSION CRITERIA :
• History suggestive of hepatitis B or C
• • History of, or clinical evidence, or suspicion, or laboratory evidence of HIV
infection.
• • Risk factors for HIV, HBV and HCV
• Presence or suspicion of central degenerative neurological
diseases of possible infectious origin, including dementia
• Septicemia and systemic viral disease or mycosis or active
tuberculosis at the time of procurement
• Presence or history of malignant disease
• Significant history of autoimmune connective tissue disease
• Significant exposure to a toxic substance that may be transferred in
toxic doses or damage the tissue
• Presence or evidence of infection
• Presence or evidence of irradiation at the site of donation.
• If the cause of death is unknown after an autopsy
• Age Criteria :
• There are no maximum age criteria if the bone is to
be morsellised, or is not to be used for weight
bearing purposes, whether procured from a
cadaver donor or from femoral heads and other
surgical residues obtained from living donors
• When large skeletal segments are obtained to
provide structural support, the donor should be free
of any significant osteoporosis and preferably below
55 years of age.
LABORATORY
TESTS
• The minimum testing universally accepted includes:
• 1. VDRL (Although there is no case of transplant - transmitted
syphilis, the VDRL test is routinely included in the screening
program for potential donors as it reflects the life-style of the
potential donor who might also harbor HIV.)
• 2. Hepatitis B surface antigen
• 3. Hepatitis C antibodies
• 4. HIV antibody
• 5. Microbiology culture of small donor tissue samples or swabs
to screen for pathogens.
TYPES OF GRAFTS
• Deep-frozen allografts
• Irradiated frozen bone
• Processed Bone
• Lyophilised, irradiated bone
• Freeze-dried, chemo
sterilized bone
TISSUE PROCESSING
Once the screening criteria have been satisfied the bones are
pasteurised

and then cut into the required shapes and sizes

The bone pieces are subsequently washed free of blood and bone marrow
using jet lavage and treated with 70 % ethanol

cleaned bones are stored at -80°C to interrupt the degradation process and
to freeze them
prior to freeze-drying

The frozen grafts are finally freeze-dried to remove 95% of the moisture
appropriately labelled and double packed

Freeze-dried samples are cultured to determine the microbiological bioburden

of the grafts
• Radiation dose is 40% above the minimum required to kill the most
radiation resistant
Bacillus pumilus E601.
• The sterility assurance level (SAL) using this dose is 10-6 which
means that the probability of failure (finding an unsterile graft) is
only one in a million provided the product has a low initial bacterial
count.
BIBLOGRAhY
• KULKARNI’S TEXTBOOK OF ORTHOPAEDICSANDTRAUMA
• BONE GRAFTS AND THEIR SUBSTITUTES JBJS 2016 98-B(1 Suppl
A):6–9.
• BONE GRAFT SUBSTITUTES FACTS, FICTIONS AND
APPLICATIONS, AAOS 2003
• Orthopaedic applications of bone graft & graft substitutes: a review
IJMR JULY 2010
• Bone Regeneration and Repair: Biology and Clinical Applications
• BASIC KNOWLEDGE OF BONE GRAFTING
THANK
YOU