1. PRESENTER: DR. SUSHIL
PAUDEL
Bone Graft Substitutes

2. Definition
Bone substitutes are natural, synthetic or composite
materials used to fill bone defects and promote bone
healing

3. Purpose
To provide:
Linkage
Splintage
and
Promote osteogenesis

4. Linkage
 Fill bony defects/cavities
 Replace crushed bone
 Arthrodesis

5. Splintage
 Non unions
 Arthrodesis

6. Why do we need them???
 2.2 million graft procedures done yearly
 9 out of 10 involve use of Auto/Allografts
 Estimated cost about $2.5 billion per year

7. Properties of an ideal bone graft
 Osteoconductive matrix
 Osteogenic cells
 Osteoinductive proteins

8. Osteoconductive matrix
Acts as a scaffold which supports osteoblasts and
progenitor cells
Provides integrated porous structure through which new
cells can migrate and new vessels can form

9. Osteogenic cells
Includes osteoblasts and osteoblastic precursors
Capable of forming new bone in proper environment

10. Osteoinductive proteins
Stimulate and support mitogenesis of undifferentiated cells
into osteoblastic cells
Bone graft substitutes have one or more of these three
properties

11. Autografts
 Harvested from the patient
 Cancellous, vascularized
cortical, non vascularized
cortical and autogeneous bone
marrow grafts
 Commonly taken from iliac
crests

12. Advantages
 No immune reaction
 All three properties present

13. Disadvantages
 Requires additional surgery
 Limited quantity
 Non availability for further surgery
 Increased morbidity
 Infection
 Chronic pain
 Cosmetic

14. Allografts
 Alternative to autografts
 Taken from donors or cadavers

15. Advantages
 Eliminates donor site morbidity
 Tackles issue of limited supply

16. Disadvantages
 Immune reaction
 Risk of infection
 Disease transmission
 Reduced osteoinductivity and osteogenecity
 Ethical issues

17. FUELLED THE QUEST
FOR NEW
ALTERNATIVES
BONE GRAFT
Disadvantages of allo/autografts

18. Classification
 Laurencin et al, proposed a classification system of material
based groups
 Includes:
Allograft based
Factor based
Cell based
Ceramic based
Polymer based

19. Allograft based
 Includes allograft bone used alone or in combination with
other material
 Available as Demineralized bone matrix, and other forms as
an autograft, Eg- corticocancellous grafts etc.

20. Dimineralized bone matrix
 Has osteoconductive and osteoinductive properties
 Does not provide structural support
 Very good for filling bone defects and cavities
 Biological activity - proteins and growth factors present in
the extracellular matrix
 Prepared by a standard process- Urist et al, modified by
Reddi and huggins

21. Pulverized allogenic bone (74-420 micrometer)
Demineralization in 0.5N HCL for 3 hours
Extra acid rinsed- sterile water, ethanol and ethyl ether

22. Uses
 Excellent for contained stable defects Eg- cysts and cavities
 Have been used for non unions and acute bone defects *
 Also been used to enhance arthrodesis Eg- spine etc.**
• *tiedmann et al, Orthopedics 1995:18 1153-8
• **Urist MR et al, Clin. Orthop. 1981;154:97-113

23.  DBM is available in various forms as
Freeze dried powder
Crushed granules, chips
Paste
Gels
mixture of DBM with autologous bone marrow has also been used as
injection*
* Connolly JF, Clin. Orthop. 1995;313:8-18

24. Product Company Type
Grafton DBM Osteotech DBM as gel, flex, putty
Dynagraft Gensci
Reg.
Process
DBM
Orthoblast DO DBM+ allograft cancellous bone
Osteofil Sofamor
Danek
DBM+gelatin carrier+ water
Opteform Exactech Compacted corticocancellous bone chips
with same material as osteofil
DBX Synthes DBM as putty, paste

26. Disadvantages
 Infection
 Disease transmission
 Variable potency- multiple donors, manufacture processes
 No RCT has been done comparing its efficacy

27. Factor based
 Involves natural or
recombinant factors
 Factors responsible for
differentiation of progenitor
cells and regulation of activity
 Mechanism of action based
mostly on activation of protein
kinases
 Combined and simultaneous
activity of various factors-
controlled resorption and
formation of bone

28. Factor+ Receptor on cell surface
Activation of protein kinases
Transcription of mRNA Proteins
Regulation of cell activity

29.  include TGF-beta, insulinlike
growth factors I and II, PDGF,
FGF, and BMPs
 Mostly in research phase
 Recombinant BMP2 as
INFUSE bone graft

30. Brief history of rhBMP2
 1965- Urist et al, isolated a group of proteins they called
BMPs
 2002- FDA approved rhBMP2 for use in lumbar spine
fusion with LT-CAGER device
 2004-FDA approved use of rhBMP2 in open tibial fractures

31. rhBMP2/ACS+allograft V/S autogeneous
bone graft in diaphyseal tibial fractures
 Study by Jones AL et al
 30 patients with diaphyseal tibial fractures with cortical bone loss
 Mean length of defect-4 cm
 Divided in 2 groups
 Short musculoskeletal function assessment administered before and after surgery
 10 in autograft group, 13 in rhBMP2 group showed healing
 Significantly less blood loss in rhBMP2 group
 Comparative improvement in SMFA in both groups
 Jones AL et al J Bone Joint Surgery AM 2006 Jul;88(2):1431-41

32. Contraindications to rhBMP2
 Hypersensitivity to rhBMP2 or bovine collagen type I
 In vicinity of resected tumor
 Patients with active malignancy or patients undergoing treatment
 Skeletally immature patient
 Pregnant women
 Patients with active infection at operative site

33. Cell based
 Based on in vitro differentiation of mesenchymal stem cells to
osteoblastic lineage
 Various additives- dexamethasone, ascorbic acid, b-glycerophosphate
 Addition of factors- TGF-beta, BMP2, BMP4, BMP7
 They have been used alongwith ceramics
 Proposed to be used in bone repair prosthetic setting

34. Ceramic based
 About 60 % bone substitutes
involve ceramics- alone or in
combination
 Eg-
Calcium sulfate
Calcium phosphate
Bioactive glass
Primary inorganic component of
bone is calcium hydroxyapatite
Property of
OSTEOINTEGRATION- newly
formed mineralized tissue forms
intimate bond with implant
material

35. Ideal ceramic
 Chemical structure to promote bone healing
 Replaced by native bone
 Mechanically strong to provide stability

36. Calcium phosphate biomaterials
 Mainly used as osteoconductive matrix
 Polycrystalline structure
 Crystals of highly oxidised material fused by sintering
 Brittle substance with poor tensile strength
 Used for filling contained bone defects and areas of bone loss
 Placed in rigidly stabilized bone or intact bone- to avoid shear stress on biomaterial
 Tightly pack in adjacent host bone to maximize ingrowth
Available as porous/non porous blocks or porous granules

37. Tri calcium phosphate
 It is a porous ceramic
 Converts partly to hydroxyapatite in the body
 More porous and faster rate of resorption than
hydroxyapatite mechanically weaker in
compression
 Unpredictable Biodegradation profile not popular
 May be used for filling bone defects- trauma, benign
tumors, cysts

38. Coralline hydroxyapatite
 Processed by hydrothermal
exchange
 Converts coral calcium
carbonate to crystalline
hydroxyapatite
 Pore diameter 200-500
micrometer
 Structure very similar to
human trabecular bone
 Contraindication to use- joint
surface defect, material may
enter joint

39.  Study show equivalent result with coralline hydroxyapatite
and autologous bone graft-tibial plateau fractures*
 Results less predictable on management of metaphyseal
fractures
* Bucholz RW clin orthop. 1989;240:53-62

40. Calcium collagen graft material
 Osteoconductive composite of
 hydroxyapatite
 calcium phosphate
 type I and III collagen
 autologous bone marrow
 Does not provide structural support
 Effective bone substitute/ bone graft expander
 Good for use in acute long bone cortical fractures

41.  No scientific evidence of benefit in management of non-
unions
 Not recommended for use in metaphyseal bone defects due
to articular fractures as provides no structural support

42. Calcium sulfate graft material
 Alphahemihydrate crystalline structure
 May be used as a bone void filler
 Completely resorbs as new bone remodels to fill defect
 Potential uses- filling defects including segmental defects,
exapanding grafts as in spinal fusion
 May be used to fill bone graft harvest sites

43.  Very limited information available regarding use in humans
 No published control studies available

44. Injectable calcium phosphate-SRS Norian
 Injectable paste of inorganic
calcium phosphate
 Hardens quickly to carbonated
apatite of low crystallinity
similar to found in mineral
phase of bone
 Within 12 hours, crystallises to
Dahlite, which can be resorbed
and replaced by host bone
 Useful to augment cast
treatment or internal fixation of
impacted metaphyseal
fractures

45.  Studies have been done in cases of impacted extra articular
distal end radius fractures with good results
 Jupiter et al. J Orthop Trauma 1997;11:110-6
 Kopylov et al. J Hand Surg [Br]. 1996;21:768-71
 Kopylov et al. Acta Orthop Scand 1999;70;1-5

46. Norian SRS in radial osteotomies
 study by Logano calderon et al
 Retrospective analysis of 6 elderly patients with corrective radial
osteotomies
 Fixed with angular stable implants+ Norian SRS
 All osteotomies healed
 Post op DASH-28 points, Modified Mayo score-68
Logan calderon et al J Hand Surg[Am] 2007 sep;32(7):976-83

47. Norian SRS in knee replacement
 Study by Mangotti A et al
 Used Norian SRS as substitute of bone graft for tibial bone
defects in TKR
 3 unicompartmental TKR, 2 revision TKR, 1 hinged knee
prosthesis
 No poor results, improved knee scores, no evidence of post
op deformity
 Mangotti A et al Arch Orthop Trauma Surg.2006 Nov:126(9):594-8

48.  Other uses:
 hip
 spine
 calcaneal
 other metaphyseal fractures
At risk of implant failure or redisplacment due to load

49. Bio active glass
 Variation of glass beads
 Composed of silica, calcium oxide, disodium oxide and
peroxide
 They bind to collagen, growth factors and fibrin to form a
matrix
 Provides compressive strength but not structural support

50. Polymer based group
 Can be divided into natural/synthetic
 Further divided into biodegradable/non biodegradable
 Eg:
 Healoss(DePuy)- natural polymer based group
polymer-ceramic composite
collagen coated with hydroxapatite
used in spinal fusions

51.  Cortoss: injectable, resin based
product for application to load
bearing sites
 Rhakoss (orthovita, inc.): Resin
composite available in various
forms for spinal fusion

52. Composite grafts
 Rationale most of the graft substitutes are only
osteoconductive
Cinolti G et al J Bone Joint Surg Br. 2004 Jan;86(1):135-42
“Osteoconductive material alone do not give effective fusion
as autologous graft”

53.  4 groups underwent Posterolateral lumbar arthrodesis
 I- Porous ceramic+mesenchymal cells
 II-Ceramic+bone marrow
 III-Ceramic alone
 IV-Autogeneous bone marrow alone

54.  Rate of fusion was much higher in I, II, IV as compared to
III
 Boden SD et al Spine.1999 feb 15;24(4):320-7
“ Coralline Hydroxyapatite+osteoinductive bone proteins give
better results in Posterolateral lumbar arthrodesis than
autograft or bone marrow extracts alone”

55. Kai T et al. Spine 2003 aug 1;28
(15):1653-8
 5 groups of rabbits underwent lumbar intervertebral spinal fusion
 I- sham operation
 II-Porous calcium phosphate ceramic alone
 III-autogeneous iliac crest
 IV- ceramic + bone marrow stromal derived osteoblasts
 V- Ceramic + bone marrow stromal derived osteoblasts + rhBMP2

56.  I-0%
 II-50%
 III-66.7% successful spinal fusion
 IV-100%
 V-100%

57.  Size of fusion mass and stiffness of fusion segments-
greatest in group V
 Conclusions:
 rhBMP2 addition may reinforce biomechanical stiffness for spinal
fusion segments
 Porous calcium ceramics should not be used alone

58. Choice of graft
 What is the expectation? Structure/bone forming function
 Availability of graft?
 Recipient bed?
 Cost?
Remember!!! Stable fixation is required for use of most
grafts

59. New concept
 Concept of tissue engineering
Application of biologic, chemical and engineering
principles
repair, restoration and regeneration of tissues
using biomaterials, cells and factors