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Bone grafts Engineering


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Bone grafts Engineering

  1. 1. Engineering of Bone Tissuefor augmentation procedures Requirements Current solutions Bi-Phasic Calcium Sulfate By Dr. Amir Kraitzer
  2. 2. Outline1. Overview2. Bone and Bone Augmentation3. Bone graft materials4. Bi-Phasic calcium sulfate Bone Graft – Bond Bone
  3. 3. Bone Augmentation• The past decade brought a new era in bone repair fueled by the latest technological advances• Part of the routine surgical spine, orthopedics and dental care• New methods and new bone grafts facilitated grafting procedures• Bone graft sources: – The patient itself – Cadavers – Animals – Synthetic• ~500,000 bone graft procedures performed in US yearly ~ 2.2 million worldwide• Estimated cost of $2.5 billion per year• Dental bone graft estimated cost 8% of total bone graft
  4. 4. Periodontal disease• Account for ~60% of tooth loss• Affect one or more of the following tissues: – alveolar bone – periodontal ligament – cementum – gingiva• Bacteria and plaque cause toxins eventually lead to inflammation
  5. 5. Outline1. Overview2. Bone and Bone Augmentation3. Bone graft materials4. Bi-Phasic calcium sulfate Bone Graft – Bond Bone
  6. 6. Bone augmentation • Following tooth extraction the alveolar ridge resorbes • Early bone loss can be reduced by socket grafting • Augmentation replaces missing bone • Grafting materials are implanted and fused with natural bone over time • Granular or block type grafts require membrane due to particle migration • Grafting procedures repair jaw bone defects: – periodontal defects – post extraction defects – bone reconstruction – implant placement – Infections – cyst or tumor surgery defectsBone Augmentation:
  7. 7. Augmentation Procedures• Grafting procedures performed primarily by periodontists or experienced dentists• Require wound healing understanding• Require knowledge of the mechanical, material and biological properties of the graft Sinus lift procedure
  8. 8. Bone StructureBone is a highly ordered structure on the macroscopic,cellular and molecular levels.• Mineralized component: 60% • Blood supply: of the bone is hydroxylapatite – Receives 5 - 10% of cardiac crystals: Ca10(PO4)6(OH)2 output• Organic matrix: 40% of the – Arterial supply bone mostly collagen – Microcirculation• Cellular components: – Venous return – Osteoprogenitor cells – Osteoblast – Osteocyte – Osteoclast
  9. 9. Bone BiologyOsteoblast• Bone forming cell• Responsible for deposition and calcification of bone matrix• Osteoblasts synthesize collagen and other proteinsOsteocyte• Mature, fully differentiated osteoblast• Surrounded by mineralized bone matrixOsteoclast• Responsible for the resorptive aspect of bone remodeling• Elaborates enzymes, acids for resorption of bone matrixOsteoprogenitor Cells• Pluripotential cells• Stem cells• Bone marrow stromal cells
  10. 10. Bone StructureBone may be classified on the basisof its clinical structure• Compact Bone (cortical) - Dense, solid bone such as the outer cortical layer• Trabecular bone (spongy or cancellous bone) - non dense bone located between compact bone.Bone anatomy and microstructure
  11. 11. Bone Structure developmentCortical or cancellous bone is of two main types• Woven (embryonic) Bone – Immature – rapidly forming bone – Randomly distributed oseocytes – poorly mineralized – structurally weak – replaced with lamellar bone• Lamellar Bone – Mature bone – Arranged parallel collagen fibers , HA and bone cells – Main load bearing component of the bone – Slowly formed (approximately 0.6 to 1 mm/ day)
  12. 12. Bone Modeling and Remodeling• Bone is capable of self-repair and adapts new loads (Wolff’s Law)• When stimulated under load the cortical portion of bone becomes thicker• Bone becomes weaker without stimulus• Two fundamental concepts, modeling and remodeling, describe the dynamic nature of bone – Remodeling - Osteoclastic resorption and osteoblastic formation is balanced – Modeling – Bone changes its 3D size and shape in response to stimulus or physical force Bone formation:
  13. 13. BONE TISSUE MECHANICAL PROPERTIES Tensile Strength (MPa) and % elongation at break ofcortical bone from the human femur as a function of age
  14. 14. OstseoporosisA disease of bones that leads to an increased risk of fracture.Remodeling imbalance between bone resorption and boneformation Healthy bone Osteoporosis
  15. 15. Outline1. Overview2. Bone and Bone Augmentation3. Bone graft materials4. Bi-Phasic calcium sulfate Bone Graft – Bond Bone
  16. 16. Mechanisms of Graft HealingAn ideal bone graft should possess the properties involved inbone healing (1) Osteoconductive – Matrix providing 3D lattice with interconnected pores – Allowing cells to migrate for ingrowth of new blood vessels and osteoprogenitor cells (2) Osteoinductive – Recruit and encourage migration of osteoprogenitor cells – Stimulating factors towards osteoblastic differentiation (3) Osteogenic – Formation of new bone from living cells transplanted within the graft
  17. 17. Bone Grafting MaterialsClassification of Grafting Materials Based on Source• Autograft (Autogenous) - Refers to a transplant of viable cortical or cancellous bone from one location to another within the same patient• Allograft- Refers to a transplant within the same species, such as the human bone sourced from cadavers.• Xenograft- Refers to a cross-species transplantation such as the use of anorganic bovine bone or bovine collagen in human subjects• Alloplast- Refers to implantation of a synthetic material. As a group, the alloplasts are synthetic osteoconductive materials.
  18. 18. Bone Grafting MaterialsAutograft• Considered the gold standard• Osteoinductive, osteoconductive, and osteogenic properties• The risk of infection is minimal• Bone is harvested from mouth, hip, iliac crest or chinDisadvantages• Low availability of bone volume• Require a second operative site• Significant patient morbidity
  19. 19. Bone Grafting MaterialsAllografts• Human cadavers source• Mineralized freeze dried allograft – Osteoconductive and Osteoinductive – Low bioavailabilty and activity of bone morphogenetic proteins (BMP)• Demineralized freeze dried bone – Osteoinductive – The process exposes BMP• BMP cause differentiation of mesenchymal cells into osteoblastsDisadvantages• Lack of uniformity in the products of individual banks• Risk of disease transmission and unpredictability• Possible infections, and antigenicity risks Grafton® DBM Gel
  20. 20. Bone Grafting MaterialsXenograft• Naturally derived hydroxylapatite from bovine, coral• Osteoconductive• Similar structure, chemistry, and porosity of human boneDisadvantages• Risk of disease transmission• Remains in the defect for years• Continuous macrophage activity Histology review: wcM&feature=channel
  21. 21. Alloplast synthetic graftsDense Hydroxylapatite• High density, high crystallinity and no resorption over time• Particles placed adjacent to bone become surrounded by bone• Particles placed more than a few millimeters are surrounded by fibrous connective tissueLow-Density Hydroxylapatite• Plasma-sprayed HA applied to implant surfaces• Amorphous• ResorbableBeta-Tricalcium Phosphate• Granular Matrix type: – Porous particles (100-300 μm) pore size – Resorbed and replaced by bone in 9 to 12 months• Cement Type: – Injected and hardens in 12 hours
  22. 22. Alloplast synthetic grafts/moreBioglass• Amorphous• Composed of calcium phosphate, sodium, and silicon• Bioactive layer for bone cell attraction to form a HA layerBioplant HTR®• Polymethyl methacrylate (PMMA) beads with a calcium hydroxide (CH) coating• Porous (350 μm) to facilitate bone ingrowth• Partially resorbable (CH)
  23. 23. Ideal Synthetic bone graft• Materials – HA or HA forming materials• Pore size, distribution, and porosity (matrix graft) – Pores of 100 m form bone (Pores of 15-40 m produce fibrous tissue) – Pore of 300-500 m permit vascular in-growth – Interconnected pores• Granule size (granular graft) – Grains larger than 10 m prevent stimulation of macrophage phgocytosis• Crystalline structure – Affect the surface adsorption of osteogenic cells – Affects mechanical and resorption profile• Mechanical properties – Should be in close proximity to the mechanical properties of bone
  24. 24. Stress Shielding• Reduced bone density due to removal of stress by an implant• Stimulus for remodeling is required to maintain bone mass (Wolffs law)• We must select materials which are in close proximity to bone’s mechanical properties
  25. 25. Density Elastic Yield strength Tensile % (g/cm3) modulus (MPa) Strength Elongation (GPa)* (MPa) at break SS 316L 7.9 190 690 860 12%30% cold worked Ti-6Al-4V or 4.5 114 830 900 14 % ASTM F136 annealed PLLA 1.3 2.7 -- 50 5 -10% Density Elastic Compressive Tensile % (g/cm3) modulus Strength Strength Elongation (GPa)* (MPa) (MPa) at breakCortical Bone ~2 17 - 24 100-230 90-130 1-3% Cancellous ~1 0.1 - 4.5 2-12 10-20 5-7% Bone *In tension
  26. 26. Resorption rate• In the early phase of healing material should remain stable• Resorbtion rate should correlate the rate of bone formation – Fast resorption compromise the osteocoductivity – Slow resorption may block bone in-growth• Homogenous solubility – Prevent premature microparticles separation ActifuseReduce macrophage phagocytosis – (Ca-Po with silicate ions replaced phosphate – Assist bone-forming metabolism groups in the calciumphosphate• ionic lattice) constant physiological concentration of calcium and phosphate ions Actifuse compared to β-TCP (VitossTM) and calcium sulfate (Osteoset TM) in the distal femoral condyle of the New Zealand white rabbit
  27. 27. Novel Bi-Phasic Calciumsulfate bone graft
  28. 28. Calcium Sulfate (CS)• Long history of use as a void filler Alderman, 1969;• First used in 1892 by Dreesmann in orthopedics Bahn, 1966;• Highly biocompatible Bell, 1964;• Osteoconductive• Fully resorbed over a period of 5–7 weeks Coetzee, 1980;• New bone formed in a normal morphology Edberg, 1930; Gitelis et al., 2001; Kelly et al., 2001;
  29. 29. The Bi Phasic Calcium Sulfate Concept Hemihydrate Dihydrate CaSO4 · 0.5H2O CaSO4 · 2H2OAdvantages Disadvantages Advantages Disadvantages• Moldable • Does not set in presence of • High strength • Non-moldable• Cementable blood/saliva • Resorption rate • Non- cementable • Low strength equivalent to bone • Fast resorption growth • Is not affected by blood and saliva
  30. 30. CS Hemihydrate + CS DihydrateBi–Phasic Calcium Sulfate
  31. 31. Bi – Phasic CS Advantages Fast and efficient setting under blood and saliva (2-5 min) High crystalline percentage Resorbtion rate equivalent to bone growth (4-10 weeks) Moldable Average reaction temperature - 30°C Neutral pH Preserves the 3D space Mechanical properties equivalent to bone
  32. 32. Future of Bone Grafts• Facilitate treatment• Enhanced resorption rate – Composite bone graft with various rates of resorption – Osteoconductive only when required• Effective and safe biological activity – Promotion of osteoblastic proliferation, differentiation and function Thank you