Bone Grafting and Bone Graft Substitutes01.pptx

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1. Bone Graft and Bone Substitutes Dr Santosh Ghimire Moderator:Asst.prof Dr Suman Dhoj Kunwar Department Of Orthopaedics Nobel Medical College

2. Bone graft are bone that is transplanted from one area of skeleton to another to aid in healing, strengthening or improving function. Bone or bone like materail used in bone graft may come from same person, from a donor or man made source.

3. BONE GRAFT INDICATIONS To promote union or fill defect in delayed union, non union, malunion , fresh fractures and osteotomies Fill cavities or defects resulting from cyst, tumors Bridge joints and perform arthrodesis Provide bone blocks to limit joint motion ( arthroereisis ) Campbell’s Operative Orthopedics. Vol 1. 14 th ed. 2021:18-26

4. BONE GRAFT INDICATIONS Bone grafting is used to improve bone fracture which are extremely complex pose a significant risk to a patient, Fracture failed to heal preoperly. Bone graft is also used to help fusion between vertebrae correct deformity provide structural support for fracture of spine In addition to fracture repair, bone graft is also used to repair in the bone caused by congenital disorder traumatic injury or surgery for bone cancer

5. Types Of Bone Graft Based on Source: Autograft, Isograft, Allograft, Xenograft Based on contents: Cortical, Cotico-canceellous, Cancellous Based on Vascularity: Vascular, Non- Vascular Based on method of preservation: fresh, frozen, freeze dried, deminieralized

6. Types Of Bone Graft Synthetic grafts or Substitutes Orthopic transfer: host site is of same tissue as that from which graft was donated. Heterotopic transfer: here bone is transferred to a new environment (eg- bone placed in a a bed of soft tissue)

7. PROPERTIES OF GRAFT Property Description Osteoinduction Process of recruitment, proliferation & differentiation of host mesenchymal stem cells into chondroblast & osteoblast Osteoconduction Process by which a graft acts as a scaffold passively hosting the necessary cells for healing Osteogenesis Ability of a material to form new bone without the requirement of outside cells Rockwood and Green’s Fracture in adult. Vol 1. 9 th ed. 2020:102-139

8. STRUCTURE OF BONE GRAFT Cancellous Advantage of rapid incorporation Lack significant structural integrity Cortical Advantage of structural integrity Trade off is delayed incorporation

9. AUTOGENOUS BONE GRAFT Transplanting bone from site of abundance to site of need within an individual Gold standard Osteoinductive , osteoconductive and osteogenic properties S.N Advantages Disadvantages 1. No processing required Donor site morbidity 2. No risk of histocompatibility and disease transmission Inherently limited supply

10. AUTOGRAFT TYPES Cancellous Cortical Free vascular transfers Muscle pedicle bone graft Bone marrow aspirate

11. BONE MARROW ASPIRATE RIA( Reamer Irrigator and Aspirators) Technique to harvest sizable amount of bone marrow, which is particularly rich in mesenchyamal stem cells Growth factors: FGF-2, IGF-2, TGF-Beta Absence of BMP-2

12. BONE MARROW ASPIRATE Advantages: Enriched osteogenesis Decrease intramedullary canal pressure Minimal risk of fat embolism Source of autologous bone, mesenchymal cells, growth factor Complications: Perforation of medullary canal Significant blood loss Fracture of donor bone

13. BONE GRAFT TECHNIQUES Onlay cortical grafts: Graft is placed subperiosteally across the fragments without mobilizing the fragments Usually supplemented with cancellous bone for osteogenesis Applied to fresh malunited and ununited fractures and bridging joints to produce arthrodesis Single and dual graft technique Most nonunion, malunion Fixation Arthrodesis

14. Inlay graft: A slot or rectangular defect is created in the cortex of the host bone A graft the same size or slightly smaller is fitted into the defect Occasionally used in arthrodesis , particularly at the ankle In treatment of diaphyseal nonunions , the onlay technique is simpler and more efficient and has almost replaced the inlay graft

15. BONE GRAFT TECHNIQUES Multiple cancellous chips: Widely used Particulary useful for filling cavities and defect, osteotomies and supplement healing Hemicylindrical grafts: Obliterating large defects Limited use Whole bone transplant: Usually fibula used Tibia and femur transplant in massive tumor recection

16. GRAFT FROM ILIAC CREST Large cancellous and corticocancellous grafts obtained from anterior superior iliac crest and posterior iliac crest In prone position posterior third used and in supine anterior third used Complications: Hernias (landslide) Neurovascular injury Cosmetic deformity Arterivenous fistula

17. GRAFT FROM ILIAC CREST Campbell’s Operative Orthopedics. Vol 1. 14 th ed. 2021:18-26

18. GRAFT FROM TIBIA Subcutaneous anteromedial is excellent for cortical graft Tibial plateau supplies cancellous graft Now rarely used due to Normal limb is jeopardized Duration and magnitude of procedure increase Ambulation of patient delayed Extra care for tibia

19. GRAFT FROM TIBIA Campbell’s Operative Orthopedics. Vol 1. 14 th ed. 2021:18-26

20. GRAFT FROM FIBULA Proximal two third of fibula can be used for bone graft Middle third can be used as vascularized free autograft based on peroneal artery and vein Patient may complain muscle pain Campbell’s Operative Orthopedics. Vol 1. 14 th ed. 2021:18-26

21. PHEMISTER BONE GRAFT Subcortical cancellous bone grafting A bone graft of cortical bone with cancellous bone chips to enhance callus formation Requisites are Mobility at fracture site should be minimal Fracture should have acceptable alignment

22. URIST AAA BONE GRAFT Composed of bone morphogenic protein, antigen extracted and autogenic bone Adjuvent treatment of nonunions

23. ALLOGRAFT One that is obtained from an individual other then the patient Limited amount of autogenic graft calls for a need of allogenic graft Indicated in elderly, children and surgical risk patients S.N Advantages Disadvantages 1. Unlimited supply Lack of osteoinductive and osteogenic properties 2. Lack of donor site morbidity Risk of disease transmission 3. Reduced mechanical properties from processing

24. ALLOGRAFT TYPES Anatomy Cortical Cancellous Osteochondral Graft processing Fresh Frozen Freeze dried Demineralized

25. BONE BANK To provide safe and useful allograft materials efficiently Donor must be screened for bacterial, viral, fungal infections Malignancy, collagen vascular disease,metabolic bone diseaseand the presence of toxins are contraindication to donation Bone and ligament and bone and tendon are banked now Articular cartilage and menisci can be cryopreserved

26. BONE BANK Bone can be sterilize in several forms Sterilised by irradiation Strong acid Ethylene oxide Bone storage Frozen (-70˚c to -80˚c) Fresh frozen is stronger then freeze dried

27. STAGES OF GRAFT HEALING Stages Activity Inflammation Chemotaxis stimulated by necrotic debris Osteoblast differentiation From precursors Osteoinduction Osteoblast and osteoclast function Osteoconduction New bone forming over scaffold Remodeling Process continues for years Miller’s review of orthopaedics . 8 th ed. 2020: 16-18

28. BONE GRAFT SUBSTITUTES Property Description Classes osteoconductive Provides passive porous scaffold to support or direct bone formation Calcium sulfate ceramics Calcium phosphate cement Collagen Bioactive glass Synthetic polymers Osteoinductive Induces differentiation of stem cells into osteogenic cells Demineralized bone matrix Bone morphogenic proteins Growth factors Gene therapy Osteogenesis Provides stem cells with osteogenic potential, which directly lays down new bone Bone marrow aspirate Combined Provides more then one properties Composites Campbell’s Operative Orthopedics. Vol 1. 14 th ed. 2021:18-26

29. BONE GRAFT SUBSTITUTES Laurencin et al divided 5 major categories Allograft based Factor based Cell based Ceramic based Polymer based

30. ALLOGRAFT BASED BONE GRAFT Preparations: Freeze dried Irradiated D ecalcified Freeze dried and irradiated obtained from cortical bone and used for structural support

31. ALLOGRAFT BASED BONE GRAFT Demineralized bone matrix (DBM) Decalcifed form of allograft that contains osteoinductive proteins for bone formation Supplied as putty, injectable gel, paste, powder, strips and mixed Carriers are glycerol, calcium sulfate powder, sodium hyluronate and gelatin Sterilization is by gamma irradiation and ethylene oxide Contraindicated in sever vascular and neurological diseases, fever, uncontrolled diabetes

32. GROWTH FACTOR BASED Bone morphogenic proteins (BMP) In 1965 urist discovered BMP BMP activites regulated by Smads and Noggin BMPs are required for skeletal development and healing Currently BMP-2 and BMP-7 are clinically approved Transforming growth factor β (TGF β ) Structurally related to BMP and uses similar set of signal transduction molecules Stimulate proliferation of differentiated cells present in young

33. The synergistic e ffect of a utograft and BMP-7 in the treatment of atrophic n onunions Giannoudis PV, Kanakaris NK, Dimitriou R, Gill I, Kolimarala V, Montgomery RJ. The synergistic effect of autograft and BMP-7 in the treatment of atrophic nonunions . Clinical Orthopaedics and Related Research®. 2009 Dec;467:3239-48 . Conclusion: Synergism exist between rnBMP and autologous bone graft Economic benefit No complication of BMP occurred during study

34. GROWTH FACTOR BASED Wnt Level of Wnt signaling regulate bone mass in the skeleton and bone healing Fibroblast growth factor (FGF) FGF contribute fracture healing by affecting angiogenesis and proliferation of MSCs Clinically rhFGF-2 applied radiological union was better Vascular endothelial growth factor (VEGF) Platelet derived growth factor (PDGF) Arachidonic acid metabolites

35. CELL BASED Mesenchymal stem cells Multipotent adult progenitor cells that give rise to bone, cartilage, muscle and other mesenchymal tissues Distributed throughout body 872 clinical trial are being performed with MSCs out of which only 17 studies testing efficacy related fracture healing Continued research is needed to realize full potential in fracture healing

36. CELL BASED Platelet concentrates Autologous blood preparations containing supra physiological concentration of activated platelets Effective platelet concentrate for bone regeneration is 2 – 6 fold increase (ideally 5 lower have no effect and higher concentrate negatively impact bone healing) Bone marrow aspirates

37. CERAMIC BASED Calcium phosphate ceramic Three general forms: Hydroxyapatite, tricalcium phosphate, calcium phosphate Differ in there rate of reabsorption and mechanical strength Hydroxyapatite reabsorbed slowest, calcium phosphate takes between 6 months to 10 years and tricalcium phosphate over 6 to 18 months Calcium phosphate cement have highest strength Advantage Disadvantage Indication Structural strength Slow / incomplete remodeling Augmentation of acute fracture fixation

38. Calcium phosphate cements Used as bone – void fillers in treatment of bony defects associated with acute fractures Inorganic calcium and phosphate combined to form paste and delivered to fracture site CPC hardens within minutes , achieving maximum compressive strength after approximately 4 hrs Strength comparable to intact cancellous bone Strength significantly diminished in torsion or shear so should be used as an adjunct rather than primary method of fixation

39. CERAMIC BASED Calcium sulfate ceramic Calcium sulfate is resorbed much more rapidly then calcium phosphate ceramic Much less biomechanical stability Advantage Disadvantage Indication Structural strength Rapid remodeling and loss of biomechanical strength Augmentation of acute fracture fixation and antibiotic delivery device

40. Affecting factors

41. POLYMER BASED Natural and synthetic Biodegradable and non biodegradable Resorption of these products limits there use in load bearing

42. Plate fixation of ununited humeral shaft fractures : Effect of type of bone graft on Healing Hierholzer C, Sama D, Toro JB, Peterson M, Helfet DL. Plate fixation of ununited humeral shaft fractures: effect of type of bone graft on healing. JBJS. 2006 Jul 1;88(7):1442-7 . Conclusion: 100% union in autogenous bone graft use and 97% union in demineralize bone graft use No significant difference in outcome of two groups Doner site related morbidity present in autologous bone graft group

43. RECENT ADVANCES 3D printing Custom made implants unique to patient bone defect Implant can be printed layer by layer using modified hydroxyapatite powder as feed material together with a polymer based binder Product is dried, cleaned at 1250˚C for two hours Clinically available in next 10 to 20 years Archunan MW, Petronis S. Bone Grafts in Trauma and Orthopaedics . Cureus . 2021 Sep 4;13(9).

44. RECENT ADVANCES Gene therapy Promising method to promote new bone growth Transfer of genetic encoding information to the target site and induce bone healing by production of specific protein Use of virus vector for the expression of BMP has been successfully demonstrated in animal models There are limitations like infection, tumor development Archunan MW, Petronis S. Bone Grafts in Trauma and Orthopaedics . Cureus . 2021 Sep 4;13(9).

45. References Campbell Operative Orthopaedics , 14 th edition Rockwodd and Green’s Fractures in Adult , 8 th edition