Bone graft substitutes


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Bone graft substitutes

  1. 1. PRESENTER: DR. SUSHILPAUDELBone Graft Substitutes
  2. 2. DefinitionBone substitutes are natural, synthetic or compositematerials used to fill bone defects and promote bonehealing
  3. 3. PurposeTo provide:LinkageSplintageandPromote osteogenesis
  4. 4. Linkage Fill bony defects/cavities Replace crushed bone Arthrodesis
  5. 5. Splintage Non unions Arthrodesis
  6. 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. 7. Properties of an ideal bone graft Osteoconductive matrix Osteogenic cells Osteoinductive proteins
  8. 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. 9. Osteogenic cellsIncludes osteoblasts and osteoblastic precursorsCapable of forming new bone in proper environment
  10. 10. Osteoinductive proteinsStimulate and support mitogenesis of undifferentiated cellsinto osteoblastic cellsBone graft substitutes have one or more of these threeproperties
  11. 11. Autografts Harvested from the patient Cancellous, vascularizedcortical, non vascularizedcortical and autogeneous bonemarrow grafts Commonly taken from iliaccrests
  12. 12. Advantages No immune reaction All three properties present
  13. 13. Disadvantages Requires additional surgery Limited quantity Non availability for further surgery Increased morbidity Infection Chronic pain Cosmetic
  14. 14. Allografts Alternative to autografts Taken from donors or cadavers
  15. 15. Advantages Eliminates donor site morbidity Tackles issue of limited supply
  16. 16. Disadvantages Immune reaction Risk of infection Disease transmission Reduced osteoinductivity and osteogenecity Ethical issues
  17. 17. FUELLED THE QUESTFOR NEWALTERNATIVESBONE GRAFTDisadvantages of allo/autografts
  18. 18. Classification Laurencin et al, proposed a classification system of materialbased groups Includes:Allograft basedFactor basedCell basedCeramic basedPolymer based
  19. 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. 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. 21. Pulverized allogenic bone (74-420 micrometer)Demineralization in 0.5N HCL for 3 hoursExtra acid rinsed- sterile water, ethanol and ethyl ether
  22. 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. 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. 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. 25. Disadvantages Infection Disease transmission Variable potency- multiple donors, manufacture processes No RCT has been done comparing its efficacy
  26. 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. 27. Factor+ Receptor on cell surfaceActivation of protein kinasesTranscription of mRNA ProteinsRegulation of cell activity
  28. 28.  include TGF-beta, insulinlikegrowth factors I and II, PDGF,FGF, and BMPs Mostly in research phase Recombinant BMP2 asINFUSE bone graft
  29. 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. 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. 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. 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. 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. 34. Ideal ceramic Chemical structure to promote bone healing Replaced by native bone Mechanically strong to provide stability
  35. 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. 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. 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. 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. 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. 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. 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. 42.  Very limited information available regarding use in humans No published control studies available
  43. 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. 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. 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. 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. 47.  Other uses: hip spine calcaneal other metaphyseal fracturesAt risk of implant failure or redisplacment due to load
  48. 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. 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. 50.  Cortoss: injectable, resin basedproduct for application to loadbearing sites Rhakoss (orthovita, inc.): Resincomposite available in variousforms for spinal fusion
  51. 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. 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. 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. 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. 55.  I-0% II-50% III-66.7% successful spinal fusion IV-100% V-100%
  56. 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. 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. 58. New concept Concept of tissue engineeringApplication of biologic, chemical and engineeringprinciplesrepair, restoration and regeneration of tissuesusing biomaterials, cells and factors