Bone graft and its substitute
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This document provides an overview of bone grafts and bone graft substitutes. It discusses what grafts and grafting are, as well as different types of bone grafts including autografts, allografts, and bone graft substitutes like demineralized bone matrix and growth factor-based substitutes. It covers the history of bone grafting, theories of graft incorporation, uses of grafts, and advantages and disadvantages of different graft options.
Bone graft and its substitute
- 1. Bone graft and its substitute Dr Kushal Shah MS ortho
- 2. Sequence of discussion • What is graft ? • What is grafting? • What are bone grafts ? • What are bone graft Substitute? • History of bone grafting • Theory of bone graft incorporation • Objectives and rationale of bone grafting • Biological concept of using bone grafts • techniques
- 3. Q What is Graft? A viable tissue that after removal from a donor site is implanted with in a recipient tissue is then restored repaired and regenerated. Q What is grafting ? Grafting is a procedure used to replace/ restore missing tissue. Q What are bone grafts ? bone grafts are the materials used for replacement or augmentation of bone. Q What are bone Substitute ? Bone substitutes are natural, synthetic or composite materials used to fill bone defects and promote bone healing
- 4. History • The principles, indication and techniques of bone grafting were established before the metalurgic age of orthopedic surgery • The first recorded bone implant was performed in 1668 by Van • Lane and sandhu introduced internal fixation • Albee,henderson,campbell intoduce the principle of osteogenesis in bone grafting.
- 5. Biological concept of using bone graft • osteoinduction – induce differentiation of stem cell into osteogenic cells • Osteoconduction- provide passive porous scaffold upon which new bone can form • osteogenesis- provide stem cell with osteogenic potential ,which directly lays down new bone • Osteopromotion: it enhances osteoinduction without possessing osyeoinductive property
- 7. Theory of bone graft incorporation
- 8. Bone Graft Uses • To fill cavities or defects resulting from cysts, tumors, or other cause • To bridge joints and provide arthrodesis. • To bridge major defects or establish the continuity of a long bone • To provide bone blocks to limit joint motion (arthrodesis) • To establish union in a pseudarthrosis • To promote union or fill defects in delayed union, malunion, fresh fractures, or osteotomies
- 9. Mesenchymal Stem cells • Progenitor cells that provide a source of cells to differentiate into chondroblasts and osteoblasts during endochondral and intramembranous bone formation • In the elderly the pool of these cells diminishes • Bone marrow is the source of adult MSCs
- 11. Autograft/ Isograft • Harvested from the patient • Gold standard • Cancellous, vascularized cortical, non vascularized cortical and autogeneous bone marrow grafts • Commonly taken from iliac crests
- 12. Adv and Disadv • No immune reaction • All three properties present • Requires additional surgery • Limited quantity • Non availability for further surgery • Increased morbidity • Infection • Chronic pain • Cosmetic
- 13. Autogenous Bone Grafts • Cancellous • Cortical • Free vascular transfers • Muscle pedicle bone graft • Bone marrow aspirate
- 14. Autogenous Cancellous Bone Grafts • Three dimensional scaffold (osteoconductive) • Osteocytes and stem cells (osteogenic) • A small quantity of growth factors (osteoinductive)ss • CREEPING SUBSTITUION: process by which graft is replaced by new bone (I year) • Used in boneloss: depressed tibial plateau fractures, revision hip and knee arthroplasty
- 15. Autogenous Cortical Bone Grafts • Sources: • Ribs • Fibula • Crest of the ilium (also called as tricortical graft) • It can be of two types: • Conventinal nov vascular • Vascularised bone graft
- 17. NV Vs Vascular graft • Non vascular • • Mainly osteoconductive • with little osteoinductive and no osteogenic properties. • • Revascularisation is slow till cortex is resorbed. • • Remodelling -2years Used in defects <6cm • Vascular • • It has immediatelyrestored blood supply • • More viable, more survival of osteocytes • • Can be used in defects upto 12 cm or even in inadequate host.
- 18. Bone Marrow Aspirate • • RIA(REAMER IRRIGATOR AND ASPIRATOR) • It is a technique to harvest sizable amount of bone marrow, which is particularly rich in mesenchymal stem cells . • Growth factors supplied: Fibroblasts growth factor(FGF)-2 Insulin like growth factor(IGF)-2
- 19. Adv and Diadv • Provides enriched osteogenesis • Decrease intramedullary canal pressure • Minimal risk of fat embolism • Potential source of autologous bone, mesenchymal cells and bone growth factors. • Perforation of the meduallary canal which • may require prophylactic intramedullary • fixation. • • Significant blood loss
- 20. Allograft • Alternative to autografts • Taken from donors or cadavers
- 21. Adv and Dis adv • Eliminates donor site morbidity • Tackles issue of limited supply • Immune reaction • Risk of infection • Disease transmission • Reduced osteoinductivity and osteogenecity • Ethical issues
- 22. Bone Graft Substitute • Ideal bone graft substitute’-should be biocompatible, bioresorbable,osteoconductive,osteoinductive, structurally similar to bone ,easy to use and cost effective.
- 23. Need for graft substitutes • Limitations of Autogenous bone graft • Increased morbidity of surgical procedure. • Increased anaesthesia time, • Increased blood loss. • Post op donor site complications • Limited amount of graft material.
- 24. Bone graft substitute- Laurencin
- 25. ALLOGRAFT BASED substitutes • Uses allograft bone with or without other elements. • Comes in many forms and many preparations-freeze dried , irradiated and decalcified. • DEMINERALISED BONE MATRIX (DBM)- chemosterilised , antigen extracted ,surface demineralised autolysed-allogeneic bone . • DBM is generally mixed with a carrier –glycerol, calcium sulfate powder, sodium hyaluronate , gelatin.
- 26. Bone Allografts • Cancellous or cortical – Plentiful supply – Limited infection risk (varies based on processing method) – Provide osteoconductive scaffold – May provide structural support
- 27. Freeze-dried – 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
- 28. • Decreases expression of MHC 1 complex in osteoblasts • • Decreased osteoinductive properties • • Reduced mechanical integrity • • Decreased number of viable cells • • Slow revascularisation and delaye remodelling • • Histologically mono nuclear cells surround the newly developed blood vessels Demineralized Bone
- 29. Demineralized Bone Matrix • Prepared from cadaveric human bone • Acid extraction of bone leaving – Collagen(type 1) – Noncollagenous proteins – Bone growth factors • BMP quantity extremely low and variable • Sterilized which may decrease the availability Available from multiple vendors in multiple preparations – Gel – Putty – Strip – Combination products with cancellous bone and other bone graft substitute produc y of BMP
- 30. Technique • Bone is collected in clean and unsterile environment. • It is nibbled to remove the articular cartilage. • It can be sterilized by irradiation, ethylene oxide or strong acid( 0.55 % HCl) • It is subject to deep freeze upto -70 to -80 degrees celcius(frozen) • Freeze drying involves removal of water and vacuum packaging of the tissue
- 31. Contd. • 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
- 32. disadv • Infection • Disease transmission • Variable potency- multiple donors, manufacture processes • No RCT has been done comparing its efficacy • DBM sterilised by gamma irradiation and ethylene oxide-1.decreases the risk of disease transmission. 2.decreases the osteoinduvtive activity. .
- 33. Contraindications to DBM1 • .Severe vascular or neurological disease. • 2.fever. • 3.Uncontrolled DM. • 4.Severe Degenerative Bone disease. • 5.Pregnancy. • 6.Hypercalcemia. • 7.Renal compromise. • 8.Pott disease,or osteomyelitis or sepsis at the surgical site
- 34. GROWTH FACTOR BASED substitutes • URIST first discovered BMP in 1965,when he recognised its ability to induce enchondral bone formation. • Growth factors are a part of a very large group of cytokines. • Growth factors commonly involved are: 1.TGF- β.2.IGF.3.PDGF.4.VEGF.5.b FGF. • Most of the BMP’s used today are in the bone super family transforming growth factor –β
- 35. • This super family includes the inhibin/activin family, mulleraian- inhibiting substance family, and the decapentaloplegic family. • IGF and TGF-β mostly modulate the synthesis of cartilage matrix. • bFGF has a powerful mitogenic factor which stimulates the differentiation of chondrocytes. • bFGF is produced locally in bone during the initial phase of fracture healing and is known to stimulate cartilage and bone forming cells.
- 36. BMP’s shown to have osteogenic properties .BMP 2,7-key role in osteoblast differentiation. .BMP-3 – induces bone formation. .BMP-4 – regulates the formation of teeth,limbs and bone from mesoderm. .BMP-5 –functions in cartilage develoment. .BMP-6- role in joint integrity in adults. BMP -8a – involved in Bone and cartilage development. BMP’s are group of noncollagenous glycoproteins that belong to the TGF-β super family.
- 37. • BMP’s are produced by recombinant technology and are designated rhBMP. • Presently only two proteins have been isolated, produced, and approved for use in humans-rhBMP-2, and rhBMP-7. • The synthetic biodegradable polymer/interconnected porous calcium hydroxyapatite ceramics(IP-CHA) composite is an excellent combination carrier/scaffold delivery system for rhBMP-2. • BMP -2,7 are water soluble and require a carrier to remain in the operative area
- 38. • MOA of rhBMP’s is :chemotaxis,mitogenesis, and cell differentiation. • rhBMP’s differ in the type of cell induced to differentiate: -rhBMP-2 acts on the mesenchymal stem cell and preosteoblast to differentiate into osteoblasts while rhBMP-7 acts only on the preosteoblast. • Uses of rhBMP’s: 1.Spinal fusion 2.Treatment of open tibial fractures. 3.Maxillofacial surgeries.
- 39. Complications of rhBMP’s • Problems with the implant-bending,breaking subsidence or migration, and loosening, • -neurological complications-paralysis,nerve and spinal cord damage,dural tears,sexual dysfunction,bowel and bladder dysfunction. • -General organ complications-respiratory failure, GIT problems.
- 40. 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
- 42. CELL BASED substitutes • Most frequently used cell based graft is autologous bone marrow. Bone marrow contains hemopoietic stem cells as well as ‘mesenchymal stem cells’ or ‘stromal cells.’ • BM stromal cells depending on the tissue environment can generate- osteoblasts,chondrocytes,adipocytes, myoblasts,endothelial cell precursors,hemopoietic stem cells.
- 43. Collection of Stem cells • Bone marrow aspiration. • Mesenchymal stem cells(MSC’s) are isolated and cultured in flasks. • After several passages ,a sufficient number of MSC are collected.Trephination and collection of MSC from the flasks. • MSC are then loaded in the scaffold. • Aspiration should be done at multiple sites to decrease dilution by blood.
- 44. Stem cell use in orthopaedic • 1.Nonunion. • 2.Delayed union. • 3.Stabilisation of fracture . • 4.Segemental bone defects. • 5.Femoral head osteonecrosis. • 6.Spinal fusion • 7.Physeal and bone cysts. 8.Osteochondral defects. 9.Articular cartilage defects.
- 45. BM aspiration procedure • Done under aseptic condition and general anaesthesia. • 3mm incision at anterior iliac crests on both sides and needles (16 or 18 guaze) passed deep into iliac crests. • BM is aspirated with 10ml syringes ,rinsed with a buffer solution containing 400ml of phosphate buffered saline solution,25000 u of heparin and 100ml of albumin,to avoid clotting. • Contents in syringes are transferred to BM collection unit,to obtain final volume of 400 ml of BM
- 46. CERAMIC BASED substitutes • Bioceramics – specially designed ceramics for the repair and reconstruction of diseased or damaged parts of the body.
- 47. Type of ceramic • 1.Dense,nonporous,nearly inert. Attach by bone growth into surface irregularities,by press fitting into a defect. (MORPHOLOGICAL FIXATION.) •Al2O3(single crystal and polycrystalline). • 2.Porous inert implant. Bone ingrowth occurs,which mechanically attaches the bone to the material. (BIOLOGICAL FIXATION.) •Al2O3(porous polycrystalline), •HA coated porous materials. • 3.Dense,nonporo us surface reactive ceramics Attach directly by chemical bonding with bone.-(BIOACTIVE FIXATION.) •Bioactive glasses. •Bioactive glass ceramics. •HA. • 4.Dense ,porous/ nonporous resorbable Slowly replaced by bone. •Calcium sulfate •TCP •Calcium phospha
- 48. BCS • About 60% BGS involves ceramics- alone or in combination • Eg : calcium sulfate, calcium phosphate, bioactive glass • • Primary inorganic componet is calcium hyroxyapatite • • Property of osteointegration, newly formed mineralised tissue forms intimate bond with implant materials
- 49. Calcium Phosphate Ceramics • 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
- 50. Tricalcium 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
- 51. Clinical use 1.powders. 2.Small unloaded implants in middle ear. 3.Dental implants with reinforcing metal ports. 4.Coatings on metal implants. 5.Low loaded porous implants where bone growth acts as reinforcing phase. 6.Bioactive phase in a polymer –bioactive ceramic composite
- 52. Calcium Sulfate(plaster of paris) • Osteoconductive void filler • Low compressive strength – no structural support • Rapidly and complete resorption • May be used as a autogenous graft extender • Pellets – Pellet injectors • Bead kits – Allows addition of antibiotics • Injectable – May be used to augment screw purchase • Combination of DMB and calcium sulfate
- 53. CAso4 -1.filling of cysts,bone cavities,benign bone lesions and segmental defects. 2.expansion of grafts used for spinal fusion. 3.filling of bone graft harvest sites
- 54. Hydroxyapatite(HA) • It is a slowly resorbing compound of calcium phosphate • Source :synthetic and animal • Hydrothermal process converts it from its native coral form to more stable HA form with pore diameters between 200 to 400 micron Hydroxyapatite • Interconnected porous structure closely resembles the porosity of human cancellous bone Cancellous Bone Hydroxyapatite • Interpore(Interpore International, Irvine,CA):first calcium phosphate based BGS approved by FDA • 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
- 55. Coralline Hydroxyapetite • 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 • Study show equivalent result with coralline hydroxyapatite and autologous bone graft-tibial plateau fractures* • Results less predictable on management of metaphyseal fractures
- 56. 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 • No scientific evidence of benefit in management of nonunions • Not recommended for use in metaphyseal bone defects due to articular fractures as provides no structural support
- 57. 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 • Very limited information available regarding use in humans • No published control studies availabl
- 58. 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 • Studies have been done in cases of impacted extra articular distal end radius fractures with good results
- 59. 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
- 60. POLYMER BASED substitutes • Polymers for graft substitutes include : -natural/synthetic. - Biodegradable/nonbiodegradable. • Nonbiodegradable natural and synthetic polymers are composites of polymer and ceramic. • Biodegradable natural and synthetic materials include -polyglycolic acid(PGA) -poly(lactic-co-glycolic )acid.