Bone Grafting and Bone

Graft
Substitutes
Dr. Himanshu Singh
MBBS, D’Ortho,
DNB resident
 Bone Graft
•
Uses
To fill cavities or defects resulting from cysts,
tumors, or other cause
• To bridge joints and provide arthrodesis
• To bridge major defects or establish the
continuity of a long bone
• To provide bone blocks to limit joint
motion (arthroereisis)
• To establish union in a pseudarthrosis
• To promote union or fill defects in delayed
union, malunion, fresh fractures, or osteotomies
s
 Mesenchymal Stem
cells
• Progenitor cells that provide a source of
cells to differentiate into chondroblasts and
osteoblasts during endochondral and
intramembranous bone formation
• In the elderly the pool of these
cells diminishes
• Bone marrow is the source of
adult MSCs
 Types of Bone Grafts:on the basis
of source
• Autogenous: source is the patient ,
usually from tibia , fibula or ilium. Also rib

• Allogenic : source is an individual other

than the patient
• Xenograft: derived from different species
Properties of auto and
allografts
 Autogenous Bone
Graft
• “Gold standard”

• May provide osteoconduction,

osteoinduction and osteogenesis
• Drawbacks
– Limited supply
– Donor site pain, haematoma, neuromas ,
fracture and heterotopic bone formation
 Autogenous Bone
Grafts
• Cancellous
• Cortical
• Free vascular transfers
• Muscle pedicle bone
graft
• Bone marrow aspirate
 Autogenous Cancellous Bone
Grafts
• Three dimensional
scaffold
(osteoconductive)
• Osteocytes and stem cells
(osteogenic)
• A small quantity of growth
factors (osteoinductive)ss
• CREEPING SUBSTITUION: process by
which graft is replaced by new bone (I
year)
 Creeping
Substituition
• Creeping substitution, the process of bone
remodeling by osteoclastic resorption and
creation of new vascular channels with
osteoblastic bone formation resulting in
new haversian systems, is the method by
which strong cortical bone is formed from
grafted material.
Autogenous Cortical Bone
Grafts
Sources:
• Ribs
• Fibula
• Crest of the ilium (also called as tricortical
graft)
• It can be of two types:
• Conventinal nov
• vascular Vascularised
bone graft
 Non vascular versus vascular
bone graft
Non vascular Vascular
• Mainly • It has
osteoconductive with immediately
littile osteoinductive restored blood
and no osteogenic supply
properties. • More viable, more
• Revascularisation survival of
is slow till cortex osteocytes
is resorbed. • Can be used in
• Remodelling - defects upto 12
 Bone Marrow
Aspirate
• RIA(REAMER IRRIGATOR AND ASPIRATOR)
• It is a technique to harvest sizable amount
of bone marrow,which is particularly rich in
mesenchymal stem cells .
• Growth factors supplied:
Fibroblasts growth factor(FGF)-2
Insulin like growth factor(IGF)-2
Transforming growth factor(TGF) beta
Absence of bone morphogenetic protein-
 Advantages of
RIA
• Provides enriched osteogenesis

• Decrease intramedullary canal pressure

• Minimal risk of fat embolism

• Potential source of autologous bone,

mesenchymal cells and bone growth
factors.
s
 Complications of
RIA
• Perforation of the meduallary canal
which may require prophylactic
intramedullary fixation.
• Significant blood loss
 Steps to minimize
risks
• Preoperatively donor radigraph should
be used to measure isthmus
• Blood should be arranged for
replacement.
• Switch off the aspirator when there is
no reaming
• Postp of ambulation should be
protective
• Check haematocrit
Wolfe kawamatto
technique
 Complications of iliac crest
• graft
Full thickness iliac crest graft lead
to herniation.
• The lateral femoral cutaneous and
ilioinguinal nerves are at risk during harvest
of bone from the anterior ilium
• Alter the contour of the anterior crest,
producing significant cosmetic
deformity
• Arteriovenous fistula, pseudoaneurysm,
ureteral injury, anterior superior iliac
Iliac crest
graft
 Grafts from
tibia
• The subcutaneous anteromedial aspect
of tibia is the source of structural
autografts.
• The plateau of tibia supplies cancellous
bone.
Tibial graft
harvest
 Disadvantages of tibial
graft
Normal limb is jeopardized

Increased duration of surgery

Protected weight bearing for atleast 6 to

12 months .
 Bone graft from
• fibula two third of the fibula can
Entire proximal
be used for bone graft
• The proximal rounded configuration of
the fibula is covered with hyaline
cartilage.
• May replace distal radius or even distal
third of fibula
• The middle third of fibula can serve as
the peroneal artery based vascular graft
 Points to remember for fibular
bone graft
• 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.
 Phemister bone
graft
• It is subcortical cancellous bone grafting

• A bone graft of cortical bone with

cancellous bone chips to enhance callus
formation.
• Bone-grafting without disturbing the
pre- existing callus
• Bone graft is taken by elevating
 Requisites for phemister
graft
• Petalling should carried out at the fracture
site
• The mobility at the fracture site should
be minimal
• The fracture should have an
acceptable alignment
• The knee joint should have a good range
 Urist AAA bone
graft
• Composed of bone morphogenic protein
and autolysed , antigen-extracted and
autogenic bone.
• h-BMP/AAA composite implants represent
adjunctive treatment of difficult
nonunions
• Composite implants may be implanted in
either partial or complete segmental
defects of long bones
 Allograft
The morbidity and limited amount of
autogenic

bone graft calls for a need of allogenic

bone Graft.

They are indicated in

[Link] 2. Elderly [Link] surgical

risk [Link] graft cannot be harvested

 Allograft
types
Cortical Cancellous
• Frozen • Frozen
• Freeze • Freeze
dried dried
 Bone
Allografts
• Cancellous or cortical
– Plentiful supply
– Limited infection risk (varies based on
processing method)
– Provide osteoconductive scaffold
– May provide structural support
 Bone
Allografts
• 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
 Bone
Bank
• It is a facilitiy to provide safe and
efficient allograft material.
• Hosts should be screened for :
infections,malignancies(except for basal
cell carcinoma of the skin), collagen
vascular diseases, metabolic bone diseases
and presence of toxins.
 Techniqu
e
• Bone is collected in clean and
unsterile environment.
• It is nibbled to remove the articular
cartilage.
• It can be sterilized by irradiation,
ethylene oxide or strong acid( 0.55 %
HCl)
• It is subject to deep freeze upto -70 to -
80 degrees celcius(frozen)
• Freeze drying involves removal of water
 Freeze dried bone
graft
• Decreases expression of MHC 1 complex
in osteoblasts
• Decreased osteoinductive properties
• Reduced mechanical integrity
• Decreased number of viable cells
• Slow revascularisation and delaye
remodelling
• Histologically mono nuclear cells surround
the newly developed blood vessels
 Demineralized Bone
•
Matrix
Prepared from cadaveric human
• bone Acid extraction of bone
leaving
– Collagen(type 1)
– Noncollagenous proteins
– Bone growth factors
• • BMP quantity extremely low and
variable
Sterilized which may decrease the
availability of BMP
 Demineralized Bone
• Matrix from multiple vendors in
Available
multiple preparations
– Gel
– Putty
– Strip
– Combination products with cancellous bone
and other bone graft substitute products
 Demineralized Bone
• Matrix
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.
 Graft
Incorporation
• Hematoma formation
– Release of cytokines and growth
factors
 Graft
Incorporation
• Hematoma formation
– Release of cytokines and growth factors
• Inflammation
– Development of fibrovascular tissue (18
hours)
 Graft
Incorporation
• Hematoma formation
– Release of cytokines and growth
factors
• Inflammation
– Development of fibrovascular tissue
• Vascular ingrowth
– Often extending Haversian canals
 Graft
Incorporation
• Hematoma formation
– Release of cytokines and growth factors
• Inflammation
– Development of fibrovascular tissue(18 hours)
• Vascular ingrowth
– Often extending Haversian canals (10 -12
days)
• Focal osteoclastic resorption of graft
 Graft
•
Incorporation
Hematoma formation
– Release of cytokines and growth factors
• Inflammation
– Development of fibrovascular tissue
• Vascular ingrowth
– Often extending Haversian canals
• Focal osteoclastic resorption of graft
• Intramembranous and/or endochondral
bone formation on graft surfaces…….
 Graft
Incorporation
• Cortical allograft
strut graft placed
next to cortex of
• host
After 4 years
of
incorporation
 Bone Graft
•
Substitutes
Need for bone graft alternatives has lead to
development of numerous bone graft substitutes
• Avoid morbidity of autogenous bone graft harvest
• Mechanical properties vary
• Most offer osteoconductive properties
• Some provide osteoinductive properties
 Bone Graft
Potential Roles
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
Properties of bone graft
substitutes
Classificatio
n
 Laurencin et al,
classification
• Allograft
based
• Factor based
• Cell based
• Ceramic based
• Polymer based
• Composite
 Ideal bone graft
•
substitute
Scaffolding for osteoconduction
• Growth factors for osteoinduction
• Progenitor cells for osteogenesis
• Biocompatible and biodegradable
and mechanical properties similar to
the surrounding bone
• Each substitute available nowadays fulfill
only some of the criteria
 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
 Bone Graft
Substitutes
• 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
 Allograft
based
• Includes allograft bone used alone or
in combination with other materials
• Available as demineralised bone
matrix
 Factor
based
• Involves natural or recombinant factors
• Factors responsible for differentiation of
progenitor cells and regulation of
activities
• Mechanism of action: based mostly
on activation of protein kinase
• Combined and simultaneous activity of
various factors controlled resorption
and formation of new bone
• Factor + receptors on the cell
surface

• Activation of protein kinase

• Transcription of mRNA

• Protein synthesis
• Includes TGF-beta, IGF-I&II,PDGF,FGF and
BMPs
• Mostly in research phase
• Recombinant BMP-2 as INFUSE bone
graft
Bone Morphogenic
Proteins
 BMP 2 and
BMP 2 7 BMP 7
• Acts as a disulfide
• It plays a key role
linked
in osteoblastic
homodimer and differentiation
helps in bone
• It induces the
and cartilage
formation prodution of SMAD
1
• It is a candidate
as retinoid • It plays a key role
mediator and in renal
helps development and
 Bone Morphogenetic
•Proteins
Produced by recombinant technology
• Two most extensively studied
and commercially available
– BMP-2 (Infuse)
Medtronics
– BMP-7 (OP-1) Stryker ss
– BMP-2 and BMP-7 are water soluble and
require a carrier to remain in the
operative area to be effective
 BMP-2 for Open Tibial
Fractures
Prospective, randomized  All received IM nail (vast
•
study majority with UNREAMED
technique) and appropriate
• 450
soft tissue management
patients
 Randomized to 3 treatments at
time of definitive wound
closure
 Placebo
 0.75 mg/ml BMP-2/ACS
 1.50 mg/ml BMP-2/ACS
BESTT Study Group, et al. J Bone Joint Surg 84A: 2123, 2002.
 Result
• s in risk of
44% reduction
nonunion/delayed union
with high dose BMP-2
• Significantly faster
fracture healing
• Significantly fewer
– invasive interventions
– hardware failures
– infections

BESTT Study Group, et al. J Bone Joint Surg 84A: 2123, 2002.
 Cell
Based
• Based on in vitro differentiation of
mesenchymal stem cells to
osteoblastic lineage
• They have been used along with
ceramics
• Proposed to be used in bone repair
prosthetic setting
 Ceramic
based
• About 60% BGS involves ceramics- alone or
in combination
• Eg : calcium sulfate, calcium
phosphate, bioactive glass
• Primary inorganic componet is
calcium hyroxyapatite
• Property of osteointegration, newly formed
mineralised tissue forms intimate bond
with implant materials
 Calcium Phosphate
Ceramics
• Enable osteoconduction but use is limited
due to poor tensile strength and
brittleness
• Injectable pastes of calcium and phospate
– Norian SRS (Synthes/Stratec)
– Alpha BSM (Etex/Depuy)
– Callos Bone Void Filler (Skeletal Kinetics)
 Calcium
Phosphat
Ceramics
• It is produced by the process of
Sintering(heating over 1000degrees C)
• Injectable
• Very high compressive strength once
hardens
• Some studies of its use have allowed
earlier weightbearing and range of
motion
 Calcium
Sulfate(plaster
of paris)
 Osteoconductive void filler
 Low compressive strength – no structural
support
 Rapidly and complete resorption
 May be used as a autogenous graft
extender
- Available from numerous companies

- Osteoset, Calceon 6, Bone Blast,

 Calcium
Sulfate
• Pellets
–Pellet injectors
• Bead kits
– Allows addition
of antibiotics
• Injectable
– May be used to
augment screw
• purchase
 Hydroxyapatite(HA
)
• It is a slowly resorbing compound of
calcium phosphate
• Source :synthetic and animal
• Hydrothermal process converts it from its
native coral form to more stable HA form
with pore diameters between 200 to 400
micron
 Hydroxyapatite

• Interconnected porous
structure closely resembles
the porosity of human Cancellous Bone
cancellous bone

Coralline hydroxyapatite
 Hydroxyapatit
•
e
Interpore(Interpore International, Irvine,CA):first
calcium phosphate based BGS approved by FDA
• Marketed as ProOsteon by Interpore Cross
• Available in various size blocks & granule
• ProOsteon 500 s
– Very slow resorption
• ProOsteon 500 R
– Only a thin layer of
HA
– Faster resorption
 Hydroxyapatite:indications
• Valgus instability following lateral
tibial plateau fracture
• Varus instability following medial
condyle fracture of tibia
• Articular incongruence of 10 mm or
more
• Translation of major condylar fragment
of more than 5mm
 Tricalcium
Phosphate(TCP)
• TCP composition is similar to calcium
and phosphate phase of human bone
and has porous nature
• TCP undergoes partial resorption and some
of it may be converted to HA once
implanted in the human body
• Complete resorption at 6 months
 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)
 Calcium Phosphate
•
Cements(CPC)
CPC is used as void filler in defects
• It consists of inorganic calcium and
phosphate combined to form an injectable
paste
 Polymer
based
• Can be divided: natural/synthetic
• Further divided into:
biodegradable/non biodegradable
• eg: Healoss(depuy)-natural
• Eg :Cortoss- injectable resin based
product
• Eg : Rhakoss(Orthovita)
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
 Composite
graft
•In this two or more type of bone graft
substitutes combined together

• So that osteoconductive and

osteoinductive properties of different BGS,
is combined
 Calcium Phosphate-Collagen
Composite
• Collagen provides binding sites for
matrix proteins
• Type I and III is added to HA,TCP and
autologous bone marrow to form a
graft material
• Although no structural support but
augments frature healing
 Bone Graft Substitute
Incorporation
• Partial incorporation
of hydroxyapatite
bone graft substitute\
• Biopsy of material
obtained 1 year
post- op