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Bone graft substitutes


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  • 1. PRESENTER: DR. SUSHILPAUDELBone Graft Substitutes
  • 2. DefinitionBone substitutes are natural, synthetic or compositematerials used to fill bone defects and promote bonehealing
  • 3. PurposeTo provide:LinkageSplintageandPromote 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 matrixActs as a scaffold which supports osteoblasts andprogenitor cellsProvides integrated porous structure through which newcells can migrate and new vessels can form
  • 9. Osteogenic cellsIncludes osteoblasts and osteoblastic precursorsCapable of forming new bone in proper environment
  • 10. Osteoinductive proteinsStimulate and support mitogenesis of undifferentiated cellsinto osteoblastic cellsBone graft substitutes have one or more of these threeproperties
  • 11. Autografts Harvested from the patient Cancellous, vascularizedcortical, non vascularizedcortical and autogeneous bonemarrow grafts Commonly taken from iliaccrests
  • 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 QUESTFOR NEWALTERNATIVESBONE GRAFTDisadvantages of allo/autografts
  • 18. Classification Laurencin et al, proposed a classification system of materialbased groups Includes:Allograft basedFactor basedCell basedCeramic basedPolymer based
  • 19. Allograft based Includes allograft bone used alone or in combination withother material Available as Demineralized bone matrix, and other forms asan 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 inthe extracellular matrix Prepared by a standard process- Urist et al, modified byReddi and huggins
  • 21. Pulverized allogenic bone (74-420 micrometer)Demineralization in 0.5N HCL for 3 hoursExtra 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 asFreeze dried powderCrushed granules, chipsPasteGelsmixture of DBM with autologous bone marrow has also been used asinjection** Connolly JF, Clin. Orthop. 1995;313:8-18
  • 24. Product Company TypeGrafton DBM Osteotech DBM as gel, flex, puttyDynagraft GensciReg.ProcessDBMOrthoblast DO DBM+ allograft cancellous boneOsteofil SofamorDanekDBM+gelatin carrier+ waterOpteform Exactech Compacted corticocancellous bone chipswith same material as osteofilDBX Synthes DBM as putty, paste
  • 25. Disadvantages Infection Disease transmission Variable potency- multiple donors, manufacture processes No RCT has been done comparing its efficacy
  • 26. Factor based Involves natural orrecombinant factors Factors responsible fordifferentiation of progenitorcells and regulation of activity Mechanism of action basedmostly on activation of proteinkinases Combined and simultaneousactivity of various factors-controlled resorption andformation of bone
  • 27. Factor+ Receptor on cell surfaceActivation of protein kinasesTranscription of mRNA ProteinsRegulation of cell activity
  • 28.  include TGF-beta, insulinlikegrowth factors I and II, PDGF,FGF, and BMPs Mostly in research phase Recombinant BMP2 asINFUSE bone graft
  • 29. Brief history of rhBMP2 1965- Urist et al, isolated a group of proteins they calledBMPs 2002- FDA approved rhBMP2 for use in lumbar spinefusion with LT-CAGER device 2004-FDA approved use of rhBMP2 in open tibial fractures
  • 30. rhBMP2/ACS+allograft V/S autogeneousbone 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
  • 31. 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
  • 32. Cell based Based on in vitro differentiation of mesenchymal stem cells toosteoblastic 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
  • 33. Ceramic based About 60 % bone substitutesinvolve ceramics- alone or incombination Eg-Calcium sulfateCalcium phosphateBioactive glassPrimary inorganic component ofbone is calcium hydroxyapatiteProperty ofOSTEOINTEGRATION- newlyformed mineralized tissue formsintimate bond with implantmaterial
  • 34. Ideal ceramic Chemical structure to promote bone healing Replaced by native bone Mechanically strong to provide stability
  • 35. 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 ingrowthAvailable as porous/non porous blocks or porous granules
  • 36. Tri calcium phosphate It is a porous ceramic Converts partly to hydroxyapatite in the body More porous and faster rate of resorption thanhydroxyapatite mechanically weaker incompression Unpredictable Biodegradation profile not popular May be used for filling bone defects- trauma, benigntumors, cysts
  • 37. Coralline hydroxyapatite Processed by hydrothermalexchange Converts coral calciumcarbonate to crystallinehydroxyapatite Pore diameter 200-500micrometer Structure very similar tohuman trabecular bone Contraindication to use- jointsurface defect, material mayenter joint
  • 38.  Study show equivalent result with coralline hydroxyapatiteand autologous bone graft-tibial plateau fractures* Results less predictable on management of metaphysealfractures* Bucholz RW clin orthop. 1989;240:53-62
  • 39. 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
  • 40.  No scientific evidence of benefit in management of non-unions Not recommended for use in metaphyseal bone defects dueto articular fractures as provides no structural support
  • 41. 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
  • 42.  Very limited information available regarding use in humans No published control studies available
  • 43. Injectable calcium phosphate-SRS Norian Injectable paste of inorganiccalcium phosphate Hardens quickly to carbonatedapatite of low crystallinitysimilar to found in mineralphase of bone Within 12 hours, crystallises toDahlite, which can be resorbedand replaced by host bone Useful to augment casttreatment or internal fixation ofimpacted metaphysealfractures
  • 44.  Studies have been done in cases of impacted extra articulardistal 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
  • 45. Norian SRS in radial osteotomies study by Logano calderon et al Retrospective analysis of 6 elderly patients with corrective radialosteotomies Fixed with angular stable implants+ Norian SRS All osteotomies healed Post op DASH-28 points, Modified Mayo score-68Logan calderon et al J Hand Surg[Am] 2007 sep;32(7):976-83
  • 46. Norian SRS in knee replacement Study by Mangotti A et al Used Norian SRS as substitute of bone graft for tibial bonedefects in TKR 3 unicompartmental TKR, 2 revision TKR, 1 hinged kneeprosthesis No poor results, improved knee scores, no evidence of postop deformity Mangotti A et al Arch Orthop Trauma Surg.2006 Nov:126(9):594-8
  • 47.  Other uses: hip spine calcaneal other metaphyseal fracturesAt risk of implant failure or redisplacment due to load
  • 48. Bio active glass Variation of glass beads Composed of silica, calcium oxide, disodium oxide andperoxide They bind to collagen, growth factors and fibrin to form amatrix Provides compressive strength but not structural support
  • 49. Polymer based group Can be divided into natural/synthetic Further divided into biodegradable/non biodegradable Eg: Healoss(DePuy)- natural polymer based grouppolymer-ceramic compositecollagen coated with hydroxapatiteused in spinal fusions
  • 50.  Cortoss: injectable, resin basedproduct for application to loadbearing sites Rhakoss (orthovita, inc.): Resincomposite available in variousforms for spinal fusion
  • 51. Composite grafts Rationale most of the graft substitutes are onlyosteoconductiveCinolti G et al J Bone Joint Surg Br. 2004 Jan;86(1):135-42“Osteoconductive material alone do not give effective fusionas autologous graft”
  • 52.  4 groups underwent Posterolateral lumbar arthrodesis I- Porous ceramic+mesenchymal cells II-Ceramic+bone marrow III-Ceramic alone IV-Autogeneous bone marrow alone
  • 53.  Rate of fusion was much higher in I, II, IV as compared toIII Boden SD et al Spine.1999 feb 15;24(4):320-7“ Coralline Hydroxyapatite+osteoinductive bone proteins givebetter results in Posterolateral lumbar arthrodesis thanautograft or bone marrow extracts alone”
  • 54. 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
  • 55.  I-0% II-50% III-66.7% successful spinal fusion IV-100% V-100%
  • 56.  Size of fusion mass and stiffness of fusion segments-greatest in group V Conclusions: rhBMP2 addition may reinforce biomechanical stiffness for spinalfusion segments Porous calcium ceramics should not be used alone
  • 57. 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 mostgrafts
  • 58. New concept Concept of tissue engineeringApplication of biologic, chemical and engineeringprinciplesrepair, restoration and regeneration of tissuesusing biomaterials, cells and factors