Bone Grafting and Bone

Graft Substitutes
Dr. Rajat Kumar Mathur
Fellow Arthroplasty
Sunshine Hospitals

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

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)
Used in boneloss: depressed tibial
plateau fractures, revision hip and
knee arthroplasty

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
Mainly
osteoconductive with
littile osteoinductive
and no osteogenic
properties.
Revascularisation is
slow till cortex is
resorbed.
Remodelling -2years
Used in defects <6cm

Vascular
It has immediately
restored blood
supply
More viable, more
survival of
osteocytes
Can be used in
defects upto 12 cm
or even in
inadequate host.

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-2

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.

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
Avoid in metabolic bone diseases

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
spine avulsion, and pelvic instability

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

Entire proximal two third of the fibula
can 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 the

osteoperiosteal flaps.

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 of motion

Urist AAA bone graft

Composed of bone morphogenic
protein and autolysed , antigenextracted and autogenic bone.
h-BMP/AAAcomposite 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
1.Children

2. Elderly 3.Poor surgical risk

4.Enough graft cannot be harvested

Allograft types
Cortical
Frozen
Freeze dried

Cancellous
Frozen
Freeze 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.

Technique
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
and vacuum packaging of the tissue

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
availability of BMP

may

decrease

the

Demineralized Bone
Matrix

Available from multiple vendors in

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 Substitutes

Potential Roles
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

Classification

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
Regulation of cell activities

 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 7
BMP 2
Acts as a disulfide
linked homodimer
and helps in bone
and cartilage
formation
It is a candidate
as retinoid
mediator and
helps osteoblastic
differentiation

BMP 7
It plays a key role in
osteoblastic
differentiation
It induces the
prodution of SMAD 1
It plays a key role in
renal development
and repair

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 study
450 patients

All received IM nail (vast

majority with UNREAMED
technique) and appropriate
soft tissue management
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.

Results
44% reduction in risk of
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 ceramicsalone 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, etc.

Calcium Sulfate
Pellets
Pellet injectors
Bead kits
Allows addition of
antibiotics
Injectable
May be used to augment
screw purchase
Combination of DMB and
calcium sulfate

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

Hydroxyapati
te
Interconnected porous
structure closely
resembles the porosity of
human cancellous bone

Cancellous Bone

Coralline hydroxyapatite

Hydroxyapatite
Interpore(Interpore International,
Irvine,CA):first calcium phosphate based BGS
approved by FDA
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

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