Allograft

allografts in periodontics

1. ALLOGRAFTS Presented By Dr. M. Shiva Shanker III Year Post Graduate Student , Dept of Periodontics, Mamata Dental College.

2. Contents Introduction History Terminology Classification of bone grafts Objectives of bone grafts Ideal characteristics of bone grafts Advantages and disadvantages Allogenous bone grafts Procurement Bone graft technique Combination procedures Recent advances Conclusion References

3. Introduction

4. History Hegedus in 1923 – transplanted autogenous bone from the tibia to the jaws to treat advanced pyorrhea. First recorded human autogenous bone graft in periodontics. Buebe and Silvers in 1936 – used boiled cow bone powder to successfully repair intrabony defects in humans. Forsberg in 1956 – Ospurum (used ox bone in human intrabony defects) Melcher in 1962 – anorganic bone ( bovine bone) in human periodontal defects

5. History contd … Scopp et al in 1966 – used Boplant Allogenic freeze dried bone – introduced in early 1970 Historically auto grafts were the first replacement grafts to be reported.

6. Terminology Graft : Any tissue or organ used for implantation or transplantation. Regeneration : is defined as the reproduction or reconstitution of lost or injured part so that form and function of lost structures are restored Periodontal Regeneration is defined histologically as regeneration of the tooth’s supporting tissues, including alveolar bone, periodontal ligament, and cementum over a previously diseased root surface. Periodontal Repair refers to the healing of a periodontal wound with tissue that restores continuity but does not fully restore the architecture and function of the support structures.

7. Terminology contd … New attachment refers to the reunion of connective tissue with a root surface that has been deprived of its periodontal ligament. Reattachment is the reunion of connective tissue with a root surface on which viable periodontal tissue is present. Nothing new is formed.

8. Terminology contd … Osteogenesis : Refers to the formation or development of new bone by cells contained in the graft. Osteoinduction : Is a chemical process by which molecules contained in the grafts convert the neighboring cells into osteoblasts which in turn form bone. Osteoconduction : Is a physical effect by which the matrix of the graft forms a scaffold that favors outside cells to penetrate the graft and form new bone.

9. Terminology contd … Bone fill is defined as clinical restoration of bone tissue in a previously treated periodontal defect. Auto graft : An auto graft is a tissue transferred from one position to a new position in the same individual. Allograft : An allograft is a tissue graft between individuals of the same species but with non identical genes. Allografts were formerly called homografts . Xenograft : A xenograft is a tissue graft between members of differing species. They were formerly called heterografts . Alloplast : An alloplast is an inert foreign body used for implantation into tissues.

10. Classification ( N asr et al 1999)

11. Rose classification

12. RATIONALE and CLINICAL OBJECTIVES Moderate-to-severe periodontal osseous defects are often not amenable to osseous resection without further compromising the support of the involved and adjacent teeth. The ideal bone replacement graft material should be able to trigger osteogenesis , cementogenesis , and a functionally oriented periodontal ligament at a more coronal level of attachment to the root surface.

13. Objectives of bone grafts ( Schallhorn , 1988): probing depth reduction, clinical attachment gain, bone fill of the osseous defect and regeneration of new bone, cementum and periodontal ligament

14. IDEAL CHARACTERISTICS OF A BONE GRAFT (Edwin rosenberg et al. 1998), Nontoxic Non antigenic Resistant to infection No root resorption or ankylosis . Strong and resilient. Easily adaptable. Readily and sufficiently available. Minimal surgical procedure. Stimulates new attachment

15. Advantages Of Bone Grafts Regeneration of the attachment apparatus. To reverse the disease process. Increased tooth support, improved function, and enhanced esthetics. Bone grafts have application of intra osseous defect and certain furcation defects.

16. Disadvantages of bone grafts ( Mellonig 1992) Increases treatment time. Additional postoperative care. The availability and added expenses Unpredictable and Technique sensitive. Graft resorption

17. Allografts : Allografts are grafts transferred between genetically dissimilar members of the same species . Three types of bone allografts are being used in periodontics. Demineralized freeze-dried bone Nondernineralized freeze-dried bone and Frozen iliac cancellous bone.

18. Advantages : Availability in adequate quantitites Predictable results Elimination of an additional donar site surgery

19. Disadvantages Host incompatiability Potentially contaminated specimens resulting in recipient site infection and potential transmission of disease from donar to recipient of the allograft

20. BONE BANKING The goals of bone banking: To preseve the integrity of the graft and the inductive protien To reduce its immunogenicity To ensure sterility

21. Pre- pocurement Notification of prospective donors death Determination of initial donor eligibility Consent Dispatch of recovery team Assignment of tracking number to prospective donor Determination of additional donor eligibility Tissue procurement

22. Procurement : Acceptance of tissue donors begins with social and medical history.

23. Exclusion of individuals (AATB, FDA) Donors from high-risk groups, as determined by medical testing and behavioral risk assessments Donors test positive for HIV antibody by ELISA Autopsy of donor reveals occult disease Donor bone tests positive for bacterial contamination Donor and bone test positive for hepatitis B surface antigen ( HBsAG ) or hepatitis C virus (HCV) Donor tests positive for syphilis.

24. Donor screening and testing Blood Serology Microbiology Autopsy Excision of Bone Allografts

25. Frozen Iliac Cancellous bone The need for extensive cross matching of donor and recipient and the possibility of disease transfer restrict the use of iliac cancellous bone. A mean coronal gain of bone amounting to 3.07mm in 26 patients at reentry has been reported. (Hiatt et al) When compared to tricalcium phosphate, frozen allogenic bone implants led to greater bone apposition and reduction in probing depth ( strub et al)

26. Leonetti et al in 2003 reported that the allogenic bone block material used for ridge augmentation and implant site was an effective alternative to harvesting and grafting autogenous bone for implant site development .

27. Freeze-Dried Bone Allograft Undemineralized FDBA was introduced to periodontal therapy in 1976 ( Mellonig et al.,1976). Freeze drying markedly reduces the antigenicity of a periodontal bone allograft (Turner and Mellonig , 1981; Quattlebaum et al, 1988).

28. Preparation of FDBA step 1. Soft tissue stripping step 2. Initial size reduction step 3. Initial cleansing and decontamination step 4. Microbiological treatment step 5. Freezing step 6. Dehydration step 7. Secondary size reduction step 8. Packaging step 9. Terminal sterilization

29. After processing Visual inspection test Residual moisture test Residual calcium test

30. Extraction socket Robert A et al in 2012 found a significantly greater new bone formation with DFDBA histologically as compared to FDBA in non-molar extraction sockets grafted for ridge preservation. Samira M. Toloue et al in 2012 reported that there was more new bone formation after 3 months in postextraction sites treated with calcium sulfate (CS) as compared to freeze-dried bone allograft (FDBA).

31. Extraction socket contd … Thomas C et al in 2015 conducted a study to examine the healing of intact extraction sockets grafted with leukocyte-platelet rich fibrin (L-PRF) as compared to freeze-dried bone allograft (FDBA) and a resorbable collagen barrier membrane (RCM ). The alveolar ridge dimension changes in intact posterior extraction sockets may be similar when either L-PRF or FDBA and RCM are utilized as socket grafting material.

32. Ortho Massoud Seifi et al in 2012 conducted a study to investigate histologic interaction following orthodontic tooth movement and concluded that FDBA and DFDBA can be used as biocompatible bone substitutes for bone defects subjected to orthodontic tooth movement.

33. Sinus lift procedure Roni kolerman et al in 2012 conducted a split mouth study to compare DBBM and FDBA in five patients undergoing bilateral maxillary sinus floor augmentation. After 9 months, core biopsy specimens were harvested. Mean newly formed bone values were 31.8% and 27.2% at FDBA and DBBM, suggesting that both materials are equally suitable for sinus augmentation.

34. Schwartz et al confirmed the hypothesis that new bone formation is dependent on the DFDBA formulation used and demonstrated that DBX, alone or in combination with other materials, can be used successfully for sinus floor elevation.

35. Andreana et al reported that calcium sulfate can be successfully used alone or in combination with DFDBA for sinus lift procedures and that possible residues of DFDBA can be found within newly generated bone.

36. Landi et al reported the combination of Osteograf /N and DFDBA appears to be osteoconductive and may be considered a valid alternative to autogenous bone grafts in sinus lift procedures .

37. Implants Joseph Nissan et al in 2009 evaluated the outcome of ridge augmentation with cancellous freeze-dried block bone allografts in the posterior atrophic mandible followed by placement of dental implants . Implant placement in the posterior atrophic mandible following augmentation with cancellous freeze-dried bone block allografts may be regarded as a viable treatment alternative

38. Fagan et al used freeze-dried mineralized bone allograft (FDBA), recombinant human platelet-derived growth factor mixture with a titanium-reinforced membrane, and a pediculated connective tissue graft (PCTG) to simultaneously augment the hard and soft tissue for delayed and immediate implant placement cases. Concluded that technique can be used effectively to simultaneously augment hard and soft tissue.

39. Intra bony defects Shigeki Ogihara et al in 2014 studied the relative efficacy of EMD/FDBA versus EMD/DFDBA when managing intrabony defects and found that both combinations resulted in greater soft tissue improvement at 1 and 3 years of follow-up compared to EMD alone.

40. Combination Tyler D. Borg et al in 2015 reported the first histologic evidence showing greater new bone formation with a combination mineralized/demineralized allograft compared to 100% mineralized FDBA in AR preservation in humans. Combination allograft results in increased vital bone formation while providing similar dimensional stability of the AR compared to FDBA alone in AR preservation.

41. Commercially available FDBA

42. Decalcified Freeze-Dried Bone Allograft Urist and co-workers showed through numerous animal experiments that demineralization of a cortical bone graft induces new bone formation and greatly enhances its osteogenic potential.

43. Preparation of DFDBA step 1. Soft tissue stripping step 2. Initial size reduction step 3. Initial cleansing and decontamination step 4. Microbiological treatment step 5. Freezing step 6. Dehydration step 7. Secondary size reduction step 8. Demineralization step 9. Buffering step 10. Final rinse step 11. Packaging step 12. Terminal sterilization

44. The sequence of bone induction with a demineralized bone graft is believed to follow a bone induction cascade ( Reddi et al, 1987; Bowers and Reddi , 1991). At day 1, there is chemotaxis of fibroblasts and cell attachment to the implanted demineralized bone matrix. At day 5, there is continued cell proliferation and differentiation of chrondroblasts . At day 7, chrondrocytes synthesize and secrete matrix. From days 10 to 12, there is vascular invasion, differentiation of osteoblasts and bone formation, and mineralization By day 21, there is bone marrow differentiation .

45. GTR Andleregg et al compared 15 pairs of periodontal osseous defects treated by GTR with DFDBA or GTR alone and found bone fill to be significantly more favorable with the use of the bone graft and the barrier. Vishal Kiran Kher et al in 2013 reported that the use of a GTR membrane with bone graft has significantly improved PPD, CAL and defect depth tested as compared with the use of bioresorbable membrane alone in the treatment of infrabony defects characterized by unfavorable architecture.

46. GTR contd … Deept Jain et al compared the efficacy of freeze-dried bone allograft (FDBA) with and without bioabsorbable guided tissue regeneration (GTR) membrane Healiguide ® in the treatment of Grade II furcation defects. There was no significant improvement in the probing depth, horizontal furcation depth, and RAL at 6 months postsurgery in the treatment of Grade II furcation defects

47. GTR contd … Zenobio et al reported that combination of GTR and DFDBA for treatment of root perforations along with periodontal surgery resulted in minimal probing depths , minimal attachment loss, and radiographic evidence of bone gain after follow-up evaluations that ranged from 2 to 4 years

48. GBR Kohal et al compared different graft materials along with GBR to evaluate the quality of implant osseointegration . I t can be concluded that the type of grafting material will not influence torque removal values, but that early membrane exposure and removal will negatively influence the torque measurements

49. Intrabony defects Simone D et al in 2011 compared the use of enamel matrix derivative (EMD) and demineralised freeze-dried bone allografts (DFDBA) with DFDBA alone for the treatment of human periodontal intrabony defects at 12 months post-surgery, At 12 months post-surgery, the combined use of DFDBA and EMD seemed to produce a statistically significant improvement of PD reduction, CAL gain,

50. Intrabony defects contd … Chhaya bansal et al in 2013 studied the efficacy of autologous PRF + demineralized freeze-dried bone allograft (DFDBA) to DFDBA alone in the treatment of periodontal intrabony defects in 10 patients. It was found that combination treatment demonstrated better results in probing pocket depth reduction and clinical attachment level gain as compared to DFDBA alone.

51. Vikas Jindal et al in 2013 compared efficacy of intra-oral autogenous graft and decalcified allogenic bone matrix (DABM) in the treatment of periodontal intrabony defects . it establishes the superiority of the intra-oral free osseous autograft over that of DABM graft in correcting the intrabony defects.

52. Intrabony defects contd … Mohana krishna et al in 2015 presented a clinical and radiographic case series on three wall intrabony periodontal defects treated with PRP and demineralized freeze dried bone allograft (DFDBA). On surgical treatment with PRP and DFDBA, six months follow up revealed a significant progress in reduction of PPD and RAL gain. Therefore, they concluded that PRP is clinically and radiographically effective in the treatment of intrabony defects.

53. Ridge augmentation Krishnajaneya reddy et al in 2015 published case reports using a novel technique of a long palatal connective tissue rolled pedicle graft with demineralized freeze-dried bone allografts (DFDBAs) plus Platelet-rich fibrin (PRF) in Class III localized anterior maxillary anterior alveolar ridge defect. They found a predictable ridge augmentation, which could be attributed to the soft and hard tissue augmentation.

54. Tetracycline Masters et al reported that there is no significant benefit from reconstituting the allograft with 50 mg/ml of tetracycline hydrochloride . Ashish et al in 2013 reported that no added benefits of local doxycycline, as compared with bone graft alone, for regeneration of non-contained human periodontal infrabony defects.

55. Mabry et al reported that the combination of local and systemic tetracycline coupled with freeze-dried bone allografts was the treatment of choice for defects associated with juvenile periodontitis.

56. combination Richard J. Miron et al in 2013 tested the ability of EMD to adsorb to the surface of DFDBA particles and determine the effect of EMD coating on downstream cellular pathways such as adhesion, proliferation, and differentiation of primary human osteoblasts and periodontal ligament cells and found that it may influence periodontal regeneration by stimulating PDL cell and osteoblast proliferation and differentiation.

57. Combination contd … Ahmad et al in 2014 histologically and histomorphometrically evaluated whether bone formation would increase by the combined use of PRGF and demineralized freeze-dried bone allograft (DFDBA ). The present study showed better socket preservation subsequent to the application of DFDBA and PRGF combination in comparison with the two other groups.

58. Combination contd … Agarwal A et al in 2015 compared PRP combined with a demineralized freeze-dried bone allograft to DFDBA with a saline solution in 48 noncontained human periodontal intrabony defects. Their findings indicate that a combination of PRP and DFDBA is more effective in such cases.

59. Comparison of FDBA and DFDBA Not demineralized better space maintenance Slower resorbtion rate compared with DFDBA Osteocondutive More radiopaque Breakdown by way of foreign body reaction Primary indication: bone augmentation associated with implant treatment . Demineralized More bone morphogenic proteins expression potential Rapid resorption Possible osteoinduction Osteoconductive More radiolucent

60. Human mineralized bone Puros (Zimmer Dental, Carlsbad, California)

61. It is human bone that undergoes a process involving delipidization with acetone and ultrasound, osmotic treatment, oxidation with hydrogen peroxide to destroy unwanted proteins, solvent dehydration with acetone to preserve the collagenous fiber structure, and low-dose gamma irradiation.

62. Christian Martin Schmitt et al in 2013 compared clinical and histological characteristics after sinus floor augmentation with biphasic calcium phosphate, anorganic bovine bone ( ABB), mineralized cancellous bone allograft ( MCBA ), or autologous bone (AB ). After augmentation of the maxillary sinus with ABB, BCP, MCBA, or AB followed by a healing period of 5 months, biopsies were taken with simultaneous implant placement. AB can be considered to remain the gold standard in sinus floor augmentation.

63. Extraction sockets Musante et al in 2013 investigated the efficacy of porous cancellous particulate allograft bone in the regeneration of post extractive sites. The radiographic and histological analyses demonstrate an optimal bone regeneration, both in terms of quality and quantity using puros .

64. James Rudolph et al in 2014 evaluated the healing of extraction sockets after implantation of a biphasic calcium sulfate (CS ) alone or in combination with a gamma-radiated human mineralized allograft. biphasic calcium sulfate combination with an allograft resulted in the greater amount of new bone formation in alveolar ridge preservation procedures.

65. Grafton DBM ( BioHorizons , Birmingham, Alabama) is processed from cadaver long bones by aseptically processing the bone to remove lipid, blood, and cellular components before it is frozen. Cortical bone is milled into elongated fibers of 0.5 mm in diameter or pulverized into particles of 100 to 500 mm. It is combined with a glycerol carrier to stabilize the proteins and improve the graft handling. It can be used in the as putty, or as matrix plugs

66. Intrabony defects Mahantesha et al in 2013 evaluated the efficacy of demineralized bone matrix (DBM) as a bone graft material in the treatment of human intrabony periodontal defects as compared with control defects treated by open flap debridement (OFD) alone. T he use of DBM was more effective than OFD in improving clinical parameters and radiographic bone fill as shown in the present study

67. Bleached Bone number of commercial bone allograft distributors promote allografts on the basis of their whiteness. Chalk white bone is bleached. Bleaching is usually achieved by bathing allografts in a solution of hydrogen peroxide [H202]. Exposure to H202 diminishes or abolishes osteoinductivity , but the effect is time-dependent. This is balanced against disinfecting activity of the compound. Holzclaw et al ., one hour exposure to H202 does not have a profound effect on osteoinduction by bone allografts

68. Safety of bone allografts There are two major concerns regarding the use of bone allografts, antigenicity and the risk of disease transmission. Antigenicity Antigenicity of the donor material arises with any dental/medical procedure using tissues derived from human donors. In humans, chromosome 6 contains the MHC, which codes for the human lymphocyte antigens. These antigens are expressed on the cell surface of nearly every nucleated cell in the body and represent the primary stimulus for transplant rejection when HLA mismatches occur between donor and recipient. Detection of donor specific anti HLA antibody formation in a patient receiving allografts is an important measure of the clinical immunogenicity of the respective graft material.

69. Risk of disease transmission The potential for disease transfer particularly viral transmission and even more particularly HIV is a crucial factor associated with use of bone allografts. First case of HIV transmission through allogenic bone was reported in 1988. Most frequently used methods of assuring graft sterility is irradiation. Smith et al reported that, even at doses at which tissue quality begins to be compromised, irradiation failed to be virucidal for HIV type 1.

70. Human Bone Allograft Tracking FDA regulations require human bone allografts must be tracked so that tissue banks and clinicians can notify recipients in the event of a product recall. HCT/P processing facilities must label each manufactured HCT/P with a unique alphanumeric identification code that does not contain the donor's name or Social Security number.

71. Bone graft technique Patient selection: Defect selection Remove all etiologic factors Flap design with a plan for closure Degranulation of defect and flap Root preparation. Encourage a bleeding bony surface Condense graft materials well Good tissue coverage Periodontal dressing Antibiotic coverage Post surgical care

72. Various forms Injectable and moldable form: alpha graft duos, AlphaGRAFT DuoFuse bone graft substitute combines the osteoinductivity of demineralized bone matrix with the osteoconductivity , moldability , structure and hard-setting characteristics of a proprietary nanocrystalline calcium phosphate technology.

73. Strip form: steri graft, Ilium Bicortical Strip, 40 mm L = 38 - 42 mm W = 19 - 25 mm T1 > 9 mm, T2 > 5 mm Ilium Bicortical Strip, 45 mm L = 43 - 47 mm W = 19 - 25 mm T1 > 9 mm, T2 > 5 mm Ilium Bicortical Strip, 50 mm L = 48 - 52 mm W = 19 - 25 mm T1 > 9 mm, T2 > 5 mm Ilium Bicortical Strip, 55 mm L = 53 - 57 mm W = 19 - 25 mm T1 > 9 mm, T2 > 5 mm Ilium Bicortical Strip, 60 mm L = 58 - 62 mm W = 19 - 25 mm T1 > 9 mm, T2 > 5 mm

74. Particulate form: 125 to 1000 μm possess a higher osteogenic potential. Optimal particle size appears to be between 100 to 300 μm . 250 to 750 μm is the most frequently available.

75. Sponge Strips (OSSIF) Sizes: 10 x 7 x 6 mm, 20 x 7x 6 mm

76. Encore The first particulate dental bone grafting product combining mineralized and demineralized bone in a single vial

77. Periomix Demineralized Bone Matrix with cancellous chips < 0.7 mm.

78. Combination procedures 89 clinicians implanted a total of 997 sites with FDBA alone and 524 sites with FDBA plus autogenous bone. Complete or >50% bone fill was obtained in 220 (67%) sites treated with FDBA and 137 (78%) of the sites treated with FDBA + A. It can be concluded that FDBA in combination with autogenous bone is more efficacious than FDBA alone, especially in furcation invasion defects.

79. A composite graft of FDBA and tetracycline in a 4:1 volume ratio has shown promise in the treatment of the osseous defects associated with localized juvenile periodontitis ( Yukna and Sepe , 1981; Evans et al, 1989). A study that compared FDBA with and without tetracycline to a nongraft procedure in 12 juvenile periodontitis patients demonstrated significantly greater bone fill and resolution of osseous defects in grafted as opposed to control sites (Mabry et al, 1985 ).

80. CONCLUSION Although bone grafts have shown to be efficacious for the treatment of periodontal osseous lesions. The reconstruction appears to be limited to a mean bone fill of approximately 3mm irrespective of the bone graft material used. Because , the ultimate goal of periodontal therapy is to reverse the disease process & completely regenerate the periodontium , additional stimuli to enhance the regenerative process is clearly needed . As there is a continuing search for new materials & new approaches for bone repair, the future of bone graft will always be expanding topic……..

81. References Clinical Periodontology, Carranza , 11 th edition. Periodontal therapy, Nabers , Stalker. Periodontics , 5 th edition, B.M.Eley , J D Manson Advances in Periodontics, Wilson, Kornman , Newman Periodontics – Daniel A. Grant Periodontics , Medicine, Surgery& Implants. Louis F. Rose, Brian C. Mealey Fundamentals of Periodontics, 2 nd edition.Thomas G. Wilson, Kenneth S. Kornmam . Evaluation of intrabony defects treated with platelet rich fibrin (or) autogenous bone graft: A comparative analysis; European Journal of Dentistry, 2015. Biomaterials for promoting periodontal regeneration in human intrabony defects; a systematic review, Periodontology 2000, 2015. Mandibular tori as bone grafts: an alternative treatment for periodontal osseous defect- clinical , radiographic and histologic morphology evaluation, JCDP-2015

82. Sinus floor augmentation with autogenous bone ( vs ) a bovine derived xenograft - a 5 year retrospective study, clinical oral implant research,2015 Vertical bone augmentation with an autogenous bone (or) particles in combination with guided bone regeneration ; a clinical and histological study, 2015. Periodontal regeneration – intrabony defects: a systematic review from the AAP regeneration workshop, 2015. Enamel matrix derivative in combination with bonegrafts : a review of literature, Quintessence international , 2014 Reconstructive surgery with chin block graft and esthetic rehabilitation of missing anterior tooth, JISP 2014. Which biomaterials may promote periodontal regeneration in intrabony periodontal defects. A systematic review, Quintessence International , 2014. Comparison of beta tricalcium phosphate and autogenous bone graft with bioabsorbable membrane and autogenous bone graft in the treatment of intrabony periodontal defects; a clinic radiographic study , Journal of Dr. NTR University of health sciences , 2014 .