This document summarizes different types of bone grafts and bone graft substitutes. It discusses autogenous bone grafts which are considered the gold standard but have limitations related to donor site morbidity. Allografts from cadaveric donors are also discussed. Bone graft substitutes described include ceramics like calcium sulfate and calcium phosphate, demineralized bone matrix, and growth factors like bone morphogenetic proteins which provide osteoinduction. The properties, advantages, and limitations of each type of graft and substitute are summarized.

1. Bone Grafting and Bone Graft
Substitutes
Dr. Gurvinder Singh
Dr. Siddharth Gupta
Residents UCMS & GTB, HOSPITAL ,DELHI

2. 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

3. s

4. 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

5. 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

6. Properties of auto and allografts

7. Autogenous Bone Graft
• “Gold standard”
• May provide osteoconduction, osteoinduction
and osteogenesis
• Drawbacks
– Limited supply
– Donor site pain, haematoma, neuromas , fracture
and heterotopic bone formation

8. Autogenous Bone Grafts
• Cancellous
• Cortical
• Free vascular transfers
• Muscle pedicle bone graft
• Bone marrow aspirate

9. 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

10. 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.

11. 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

12. 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.

13. 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

14. 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.

17. s

18. Complications of RIA
• Perforation of the meduallary canal which
may require prophylactic intramedullary
fixation.
• Significant blood loss

19. 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

20. Wolfe kawamatto technique

21. 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

23. Iliac crest graft

24. Grafts from tibia
• The subcutaneous anteromedial aspect of
tibia is the source of structural autografts.
• The plateau of tibia supplies cancellous bone.

25. Tibial graft harvest

26. Disadvantages of tibial graft
 Normal limb is jeopardized
 Increased duration of surgery
 Protected weight bearing for atleast 6 to 12
months .

27. 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

28. 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.

29. 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.

30. 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

31. 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

32. 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

33. Allograft types
Cortical
• Frozen
• Freeze dried
Cancellous
• Frozen
• Freeze dried

34. Bone Allografts
• Cancellous or cortical
– Plentiful supply
– Limited infection risk (varies based on processing
method)
– Provide osteoconductive scaffold
– May provide structural support

35. 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

36. 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.

37. 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

40. 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

41. 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

42. Demineralized Bone Matrix
• Available from multiple vendors in multiple
preparations
– Gel
– Putty
– Strip
– Combination products with cancellous bone and
other bone graft substitute products

43. 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.

44. Graft Incorporation
• Hematoma formation
– Release of cytokines and growth factors

45. Graft Incorporation
• Hematoma formation
– Release of cytokines and growth factors
• Inflammation
– Development of fibrovascular tissue (18 hours)

46. Graft Incorporation
• Hematoma formation
– Release of cytokines and growth factors
• Inflammation
– Development of fibrovascular tissue
• Vascular ingrowth
– Often extending Haversian canals

47. 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

48. 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…….

50. Graft Incorporation
• Cortical allograft strut
graft placed next to
cortex of host
• After 4 years of
incorporation

51. 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

52. 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

53. Properties of bone graft
substitutes

54. Classification

55. Laurencin et al, classification
• Allograft based
• Factor based
• Cell based
• Ceramic based
• Polymer based
• Composite

56. 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

57. 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

58. 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

59. Allograft based
• Includes allograft bone used alone or in
combination with other materials
• Available as demineralised bone matrix

60. 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

61. • Factor + receptors on the cell surface
• Activation of protein kinase
• Transcription of mRNA
• Protein synthesis
• Regulation of cell activities

62. • Includes TGF-beta, IGF-I&II,PDGF,FGF and
BMPs
• Mostly in research phase
• Recombinant BMP-2 as INFUSE bone graft

63. Bone Morphogenic Proteins

64. 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

65. 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

66. 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.

67. 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.

68. 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

69. 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

70. 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)

71. 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

72. 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.

73. 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

74. 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

75. Hydroxyapatite
• Interconnected porous
structure closely resembles the
porosity of human cancellous
bone
Cancellous Bone
Coralline hydroxyapatite

76. 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

77. 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

78. 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

79. 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)

80. 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

81. 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)

82. 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

83. 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

84. 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

85. Bone Graft Substitute Incorporation
• Partial incorporation of
hydroxyapatite bone
graft substitute
• Biopsy of material
obtained 1 year post-op