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Bone grafting and bone graft substitutes

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Bone grafting and bone graft substitutes

  1. 1. Bone Grafting and Bone Graft Substitutes Dr. Junaid khan Supervisor : Dr. Tashfeen Ahmed
  2. 2. BONE GRAFT INDICATIONS • Structural support of articular fracture – Tibial plateau fracture – Prevent post-op collapse • Void filler to prevent fracture – Cyst excision • Improved healing of fracture and nonunions – Speed healing – Fewer nonunions • To bridge joints and provide arthrodesis
  3. 3. CLASSIFICATION Bone grafts Bone graft substitutes Autografts Allografts •Cortical •Cancellous •Corticocancellod •Vascularized •Bone marrow aspirate •Fresh •Fresh frozen •Fresh dried •Demineralized freeze-dried •Calcium phosphate •Calcium sulfate •Collagen based matrices •Hydroxyapatite •Tricalcium phosphate osteoconductive osteoinductive ostegenective combined •Demineralized bone matrix •BMPS •Bone marrow aspirates •composites
  4. 4. MECHANISMS • Osteoconduction – Provides matrix for bone growth • Osteoinduction – Growth factors encourage mesenchymal cells to differentiate into osteoblastic lineages • Osteogenesis – Transplanted osteoblasts and periosteal cells directly produce bone
  5. 5. OSTEOCONDUCTION • This process supplies the three-dimensional configuration as a sca old for the ingrowthff into the graft of host capillaries, perivascular tissue and osteoprogenitor cells from the recipient.
  6. 6. OSTEOINDUCTION • possess a chemical matrix, which provides molecular signals to the host that recruit or stimulate cellular activity for bone regeneration. • The signals are the bone morphogenetic protein (BMPs), transforming growth factors (TGFs), platelet-derived growth- factor (PDGF).
  7. 7. OSTEOGENESIS • physiologic process whereby new bone is synthesized by graft cells or cells of the host.
  8. 8. • This new bone initially may be important for the development of callus during early graft incorporation.
  9. 9. TYPES OF BONE GRAFTS • Autograft • Allograft • Bone graft substitutes – Most have osteoconductive properties • Osteoinductive agents – rhBMP-2 (Infuse) and rhBMP-7 (OP-1)
  10. 10. AUTOGRAFTS
  11. 11. AUTOGENOUS BONE GRAFT • “Gold standard” • May provide osteoconduction, osteoinduction and osteogenesis • Drawbacks – Limited supply – Donor site morbidity
  12. 12. CORTICAL BONE GRAFTS • Less biologically active than cancellous bone – Less porous, less surface area, less cellular matrix – Prologed time to revascularizarion • Provides more structural support – Can be used to span defects • Vascularized cortical grafts – Better structural support due to earlier incorporation
  13. 13. CANCELLOUS BONE GRAFTS • Three dimensional scaffold (osteoconductive) • Osteocytes and stem cells (osteogenic) • A small quantity of growth factors (osteoinductive) • Little initial structural support • Can gain support quickly as bone is formed
  14. 14. VASCULARIZED GRAFTS • Bone is transferred with its blood supply which is anastomosed to vessels at recipient site. • Available donor sites: o Iliac crest (with one circumflex artery) o Fibula (peroneal artery) o Radial shaft (interosseus artery)
  15. 15. • Vascularized grafts remain completely viable and incorporated like that of fracture healing
  16. 16. AUTOGRAFT HARVEST • Cancellous – Iliac crest (most common) • Anterior- taken from gluteus medius pillar • Posterior- taken from posterior ilium near SI joint – Metaphyseal bone • May offer local source for graft harvest – Greater trochanter, distal femur, proximal or distal tibia, calcaneus, olecranon, distal radius, proximal humerus
  17. 17. AUTOGRAFT HARVEST • Cancellous harvest technique – Cortical window made with osteotomes • Cancellous bone harvested with gouge or currette – Can be done with trephine instrument • Circular drills for dowel harvest • Commercially available trephines or “harvesters” • Can be a percutaneus procedure
  18. 18. AUTOGRAFT HARVEST • Cortical – Fibula common donor • Avoid distal fibula to protect ankle function • Preserve head to keep LCL, hamstrings intact – Iliac crest • Cortical or tricortical pieces can be harvested in shape to fill defect
  19. 19. ALLOGRAFTS
  20. 20. – Used in small children where suffiecient graft is not available from donor site – In adults where large defects have to be filled like: o Periprosthetic long bone fracture o Revision Total joint surgeries. o Reconstruction after tumor excision
  21. 21. BONE ALLOGRAFTS • Available in various forms – Processing methods may vary between companies / agencies • Fresh • Fresh Frozen • Freeze Dried
  22. 22. FRESH BONE ALLOGRAFT – Limited time to test for immunogenicity or diseases – Highly antigenic – Risk of transmission of diseses – considerable risk of rejection (about 50%) – Use limited
  23. 23. FRESH FROZEN ALLOGRAFTS Fresh frozen bone (FFB) is exposed to temperatures below -70°C – Less antigenic – Time to test for diseases – Strictly regulated by FDA – Preserves biomechanical properties • Good for structural grafts
  24. 24. FREEZE-DRIED BONE ALLOGRAFTS • To prepare a freeze-dried bone allograft (FDBA), in addition to freezing, the donor bone is defatted, the bone marrow is removed, and it is dehydrated using different solvents. – 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
  25. 25. DEMINERALIZED FREEZE-DRIED BONE ALLOGRAFT (DFDBA) • the HA skeleton of the allograft is removed using hydrochloric acid, with the aim of exposing the osteoinductive molecules in the allograft additionally
  26. 26. BONE GRAFT SUBSTITUTES
  27. 27. BONE GRAFT SUBSTITUTES • They are synthetic or composite materials used to fill bone defects and promote bone healing. • Avoid morbidity of autogenous bone graft harvest • Mechanical properties vary • Most offer osteoconductive properties • Some provide osteoinductive properties
  28. 28. Bone Graft Substitutes • 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
  29. 29. Bone Graft Substitutes
  30. 30. 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
  31. 31. • 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
  32. 32. CALCIUM PHOSPHATE • Injectable pastes of calcium and phospate – Norian SRS (Synthes/Stratec) – Alpha BSM (Etex/Depuy) – Callos Bone Void Filler (Skeletal Kinetics)
  33. 33. Norian SRS
  34. 34. • Injectable • Very high compressive strength once hardens • Some studies of its use have allowed earlier weightbearing and range of motion
  35. 35. How it works ? – Provides a porous scaffold that resorbs overtime • Osteoclast cells begin recycling the material at the junction between bone and cement almost immediately • Growth factors and antibiotics can be added to the paste in order to compliment the natural regeneration process • After healing, all of the cement is replaced with natural new bone tissue
  36. 36. • Osteoconductive void filler • Low compressive strength – no structural support • Rapidly resorbs • May be used as a autogenous graft extender - Available from numerous companies - Osteoset, Calceon 6, Bone Blast, etc. CALCIUM SULFATE
  37. 37. • Pellets – Pellet injectors • Bead kits – Allows addition of antibiotics • Injectable – May be used to augment screw purchase Calcium Sulfate
  38. 38. 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)
  39. 39. HYDROXYAPATITE • Produced from marine coral exoskeletons that are hydrothermically converted to hydroxyapatite, the natural mineral composition of bone • Interconnected porous structure closely resembles the porosity of human cancellous bone Coralline hydroxyapatite Cancellous Bone
  40. 40. Hydroxyapatite • 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
  41. 41. 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
  42. 42. DEMINERALIZED BONE MATRIX • Prepared from cadaveric human bone • Acid extraction of bone leaving – Collagen – Noncollagenous proteins – Bone growth factors • BMP quantity extremely low and variable • Sterilized which may decrease the availability of BMP
  43. 43. • Available from multiple vendors in multiple preparations – Gel – Putty – Strip – Combination products with cancellous bone and other bone graft substitute products Demineralized Bone Matrix
  44. 44. • 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. Demineralized Bone Matrix
  45. 45. Bone Morphogenetic Proteins • Produced by recombinant technology • Two most extensively studied and commercially available – BMP-2 (Infuse) Medtronics – BMP-7 (OP-1) Stryker Biotech • Used in treatment of non union and open tibial fracture
  46. 46. GRAFT INCORPORATION
  47. 47. Graft Incorporation • Hematoma formation – Release of cytokines and growth factors • Inflammation – Development of fibrovascular tissue • Vascular ingrowth – Often extending Haversian canals
  48. 48. Primary phase • Hemorrhage • Inflammation • Accumulation of hemopoitic cells including neutrophills, macrophages, and osteoclasts • Removal of necrotic bone
  49. 49. • Osteoconductive factors released from graft during resorption and cytokines released during inflammation • Recruitment and stimulation of mesenchymal stem cells to osteogenic cells • Active bone formation
  50. 50. Second phase • Osteoblasts lines dead trabeculae and lay down osteoid • Haemophoitic marrow cells forms new marrow in transplanted bone • Remodelling ie woven bone slowly being transformed into lamellar bone by coordinated activities of osteoblasts and osteoclasts. • Incorporation of grafts
  51. 51. Host response to cancellous vs cortical BG • In cortical bone graft first osteoclastic resorption then osteoblastic activity • Where as in cancellous bone graft bone formation and resorption occurs simulaneously called creeping substitution • Therefore cancellous bone graft incorporates quickly • But does not provides immediate structural support
  52. 52. Graft Incorporation • Cancellous bone interface between graft and host bone
  53. 53. Graft Incorporation • Cortical allograft strut graft placed next to cortex of host • After 4 years of incorporation
  54. 54. • Partial incorporation of hydroxyapatite bone graft substitute • Biopsy of material obtained 1 year post-op Bone Graft Substitute Incorporation
  55. 55. FACTORS INFLUENCING GRAFT INCORPORATION
  56. 56. Various bone graft techniques
  57. 57. ONLAY CORTICAL GRAFT • Graft is palced subperiosteally across the fragment without mobilizing the fragmengts • Cortical graft was suplemented with cancellous bone
  58. 58. Advantages • Simple to do • Blood supply of the fragment and the normal impacting forces of the fracture is not disturbed
  59. 59. Uses • Malunited, nonunited fractures of shaft of long bone • Bridging joints to produce arthrodesis • Fixation is achieved by internal or external metallic devices.
  60. 60. DUAL ONLAY GRAFT • Two cortical onlay grafts are placed opposite each other on the host bone across the nonunion and are fixed with the same set of screws • They grip the fragments like a vise
  61. 61. Uses • To fix non united short osteoporotic fracture near a joint • Non union
  62. 62. Advantages • Mechanical fixation is better than fixation by a single onlay bone graft • Two grafts add strength and stability • Grafts from a trough into which cancellous bone may be packed • During healing the dual graft prevent contracting fibrous tissue from compromising transplanted cancellous bone.
  63. 63. Disadvantages • Not as strong as metallic fixator devices • Extremity usually must serve as a donor site if autogenous graft are used • The surgery necessary to obtain them has more risk
  64. 64. INLAY GRAFTS • A slot rectangular defect is created in the cortex of host bone then a graft of the same size or slighly smaller is fitted in the defect • Ocasionally used in arthrodesis, particularly at the ankle
  65. 65. Multiple cancellous chip grafts • Useful for : 1.Filling defects or cavities resulting from cysts, tumors etc 2.For establishing bone blocks and for wedging in osteotomies
  66. 66. HEMICYLINDRICAL GRAFTS / MASSIVE SLIDING GRAFTS A massive hemicylindrical cortical grafts from the affected bone is placed across the defect and supplimented by cancellous iliac bone Suitable for obliterating large defects of the tibia and femur Applicable for resection of bone tumor when amputation is to be avoided
  67. 67. Indications for Bone Graft • Provide mechanical support – Metaphyseal impaction – 27 y.o male with lateral split/depression tibial plateau fracture. Note posterolateral depression.
  68. 68. Indications for Bone Graft • Provide mechanical support – Metaphyseal impaction – ORIF with allograft cancellous bone chips to fill defect and support depressed area – Alternatively could use any osteoconductive substitute with similar compressive strength
  69. 69. Indications for Bone Graft • Provide mechanical support – Metaphyseal impaction – 4 months s/p surgery and the graft is well incorporated.
  70. 70. Indications for Bone Graft • Provide mechanical support – Metaphyseal impaction • Replace bone – Cortical or segmental defect • Stimulate healing – Atrophic and Oligotrophic Nonunions – 26 y.o. woman with established atrophic nonunion of the clavicle.
  71. 71. Indications for Bone Graft • Provide mechanical support – Metaphyseal impaction • Replace bone – Cortical or segmental defect • Stimulate healing – Atrophic and Oligotrophic Nonunions – Plating with cancellous iliac crest autograft.
  72. 72. Indications for Bone Graft • Provide mechanical support – Metaphyseal impaction • Replace bone – Cortical or segmental defect • Stimulate healing – Atrophic and Oligotrophic Nonunions – 6 months after surgery, she is healed and asymptomatic.
  73. 73. Indications for Bone Graft • Provide mechanical support – Metaphyseal impaction • Replace bone – Cortical or segmental defect • Stimulate healing – Nonunions – Arthrodesis – Failed subtalar arthrodesis
  74. 74. Indications for Bone Graft • Provide mechanical support – Metaphyseal impaction • Replace bone – Cortical or segmental defect • Stimulate healing – Nonunions – Arthrodesis – Repeat fusion with autogenous iliac crest.
  75. 75. Indications for Bone Graft • Provide mechanical support – Metaphyseal impaction • Replace bone – Cortical or segmental defect • Stimulate healing – Nonunions – Arthrodesis – 6 months after surgery, fused successfully
  76. 76. Q.1 You are planning surgery on a 54-year-old female with the tibial plateau fracture seen in figures A and B. After reduction of the joint surface you plan to fill the void with a bone-graft substitute to prevent joint collapse. Which of the following bone-graft substitutes disappears most quickly in vivo? A B
  77. 77. Q.2 • Which of the following bone graft material contains live mesenchymal osteoblastic precursor cells?
  78. 78. Q.3
  79. 79. q.4
  80. 80. Q 5
  81. 81. Q.6
  82. 82. Q 7
  83. 83. Thank You

Editor's Notes

  • Bone grafts, and bone graft substitutes, are used primarily for three main purposes. One, to provide structural support, such as after elevation of a depressed tibial plateau fracture. Second, to fill a void, such as after excision of a bone cyst in an area that does not demand any structural support. Third, to improve fracture healing. Either by speeding healing or increasing the successful union rate.
  • Surface cells, which survive with transplantation of either cortical or cancellous grafts, can produce new bone.
  • Note that cancellous bone, because of its large surface area, has a greater potential for forming new bone than does cortical bone
  • The most common form of autogenous bone graft is cancellous bone, usually harvested from either anterior or posterior iliac crests, but which also may be harvested locally such as in the proximal tibia or distal radius. Cortical bone strips may be harvested from the inner table of the pelvis. Occasionally a vascularized bone graft may be used, such as a free fibular transfer. Another option for obtaining osteogenic cells is by bone marrow aspirate.
  • Autogenous bone or autograft is bone transplanted within the same individual
  • Calcium phosphate products are an injectable paste of calcium and phosphate.
    Norian SRS was the first such product available and is marketed by Synthes / Stratec.
    Two other calcium phosphate type products are also available in the U.S.
  • Medical grade calcium sulfate is an osteoconductive void filler. It has low compressive strength so doesn’t offer structural support. Another disadvantage of the product is that it resorbs rather rapidly, perhaps more rapidly then it can be replaced by new bone.
  • Calcium sulfate products are available both as pellets, bead kits, and injectable preparations. The pellets can be poured into position, but some companies also provide an injector apparatus. The bead kits allow the addition of antibiotics if desired.
  • Two bone morphogenetic proteins are commercially available. These are BMP-2,marketed by Medtronics, and BMP-7, more commonly known of osteogenic protein 1, produced by Stryker Biotech.
    These products are produced by recombinant technology in which large quantities of the material are produced in cell culture.
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