This document discusses periodontal regeneration techniques. It covers topics like guided tissue regeneration (GTR), bone grafts, growth factors and their role in treating periodontal defects. GTR uses barrier membranes to prevent epithelial down growth and help regenerate periodontal tissues. Studies show that GTR is effective in treating intra-bony defects and class II mandibular furcations, but has limited effects on maxillary furcations. GTR alone or with grafts can treat gingival recession. Long-term results of GTR are stable over many years.

1. Periodontal
Regeneration
1

2. 100 marks
 Recent advances in use of bone grafts in the treatment of
periodontal defect
 Bone grafts in periodontics- to be or not to be
 Application of tissue engineering in periodontal defect
 Periodontal regeneration
 Regenerative osseous surgery
 Current status of GTR
 GTR
2

3. 20 marks
 Approaches for tissue engineering
 Biologic principles of GTR
 PRP
 New attachment procedure
 Reconstructive osseous surgery
3

4. 7 marks
 PRP
 Current concepts in root
biomodification
 Significance of root surface therapy
 Materials used in GTR
 Bioabsorbable membrane
 Autogenous bone graft
 Techniques used for harvesting
autogenous bone graft
 Classification of various bone graft
 Allografts
 Current status of alloplast
 Alloplastic bone graft substitutes
 Vascular endothelial growth factor
 Growth factors
 Status of growth factors in
periodontal regeneration
4

5.  BMP
 Autogenous bone growth
 Techniques used in harvesting
autogenous bone graft
 PRP
 Current concepts in root
biomodification
 Current status of alloplasts in
periodontal regeneration
 Classification of various bone
grafting material
 Material used in GTR
 Significance of root surface therapy
 Allografts
 EMD
 Bioabsorbable membrane
 Current concept of new attachment
5

6. Indications & Contraindications
Indications
 Intrabony defects
 Furcation involvements
 Recessions
 Ridge augmentations
 Sinus procedures
 Implant related
Contraindications
 Horizontal defects
 Medically compromised patients not
fit for the procedure.
6

7. Terminology7

8.  Regeneration refers to the reproduction or reconstitution of a lost or injured
part
 Repair, describes healing of a wound by tissue that does not fully restore
the architecture or the function of the part
 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.
8

9.  New attachment is defined as the union of connective tissue or epithelium
with a root surface that has been deprived of its original attachment
apparatus.
 The term reattachment was used to describe the regeneration of a fibrous
attachment to a root surface surgically or mechanically deprived of its
periodontal ligament tissue,
American Academy of Periodontology 2001
Wang et al. 2005
9

10. Successful periodontal regeneration relies
on
 The re-formation of an epithelial seal,
 Deposition of new acellular extrinsic fiber cementum
 Insertion of functionally oriented connective tissue fibers into the root
surface, and
 Restoration of alveolar bone height
Villar and Cochran 2010
10

11. Therapeutic End-Points of Success
 Gain of clinical attachment,
 Fill of the intra bony component of the defect,
 Fill of the Furcation defect
 Reduction of pocket depth and
 Minimal gingival recession
Cortellini and Tonetti 2000
11

12. The main methods used for evaluation
 Clinical measurements,
 Radiographic analysis,
 Direct measurement of bone or Surgical re-entry, and
 Histology
Reddy and Jeffcoat 1999
12

13. Melcher’s Hypothesis13

14.  The ultimate goal of periodontal therapy is full regeneration of the
Periodontium destroyed by Periodontitis, to their original form, function,
and consistency.
 Melcher suggests that, under physiological conditions, the type of cells
that repopulate the wound area will determine the type of attachment
Melcher AH (May 1976). "On the repair potential of periodontal tissues". J.
Periodontol. 47 (5): 256–60.
14

15. Melcher1976
1. Epithelial cells
2. Connective tissue cells
3. Bone cells
4. Periodontal ligament cells
15

16. 16
Gingival epithelium-Long JE Gingival connective tissue
Root resorption
Bone-Ankylosis
PDL cells- New
attachment

17. Different regenerative materials / methods
GTR
Bone grafts
Root conditioning
Enamel Matrix Derivatives
Platelet concentrates & Growth factors
Tissue engineering and Stem cell therapy
Gene therapy
Laser Assisted Regenerative (LAR) therapy
17

18. The hierarchy
Evidence based approach
Meta analysis and systematic
reviews
RCT’s
Cohort studies
Case control studies
Case reports
Ideas, editorial, opinion
Animal research
In vitro research
18

19. Evidence-based Regenerative strategy
 Patient factors
 Morphology of the defect
 Access Surgery (PPF, MPPF, SPPF, MIST, M-MIST)
 Appropriate choice of regenerative therapy/material,
 Suturing techniques
 The healing period
Cortellini and Tonetti 2000a, 2005
19

20. Operative Decision Trees
 Selection of the patient
 Less than 15% of sites presenting with plaque and residual infection,
 Nonsmokers with a high degree of compliance, and
 Systemically healthy individuals
 Selection of defect
 Defects presenting with a radiographic angle of 25° or less,
 An intrabony component deeper than 3 mm and
 Gingival tissues at least 1 mm thick
Tooth factors
 Deep and narrow intrabony defects at either vital or endodontically treated teeth
 Baseline mobility amounting to less than 1 mm horizontally
Cortellini and Tonetti (2000)
20

21. Decision tree: non-esthetically sensitive sites21
Cortellini and Tonetti 2000

22. Decision tree: esthetically sensitive sites22
Cortellini and Tonetti 2000

23. Guided tissue regeneration
The Barrier concept
23

24. Rationale
 Barrier membranes
 Prevents epithelial down growth
 Stabilize the blood clot
 Helps repopulate the area with cells originating from intact periodontal
ligament and alveolar bone
Nyman et al. 1980, 1982
Gottlow et al. 1984, 1986
Karring et al. 1980, 1985, 1993
Cortellini and Tonetti 2000
Bosshardt and Sculean 2009
24

25. The Qualities of an “Optimal GTR Barrier”
for Periodontal Regeneration
 Safety requirements
 Biocompatible
 Reliable cervical anchorage and sealing around the tooth
 Space-making for selective tissue regeneration
 Barrier stability for clot protection
 Barrier tissue integration and prevention of barrier exposure
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26.  Adapted barrier permeability
 Sufficient function time for periodontal regeneration to occur
 Ease of clinical handling
Gottlow 1993
Hugoson et al. 1995
Hardwick et al. 1995
Hämmerle and Jung 2003
26

27. Clinical Applications
 Intrabony defects
review by Cortellini & Bowers 1995,
 Furcation involvements
review by Machtei & Schallhorn 1995; Karring & Cortellini 1999,
 Localized gingival recession defects
Pini-Prato et al. 1996
27

28. Histological Studies
 Documented proof of promoting new attachment in
 Animal studies
Aukhil et al. 1983, 1986; Caffesse et al. 1988, 1994; Caton et al. 1992; Gottlow et
al. 1984, 1994; Nyman et al. 1982a; Elharar et al. 1998; Batista et al. 1999;
Blumenthal et al. 2003
 Human biopsy material
Becker et al. 1987; Cortellini et al. 1993a, b; Gottlow et al. 1986; Nyman et al.
1982b; Stahl and Froum 1991; Stahl et al. 1990; Laurell et al. 2006
28

29. Efficacy of GTR in the Treatment
Infrabony Defects
29

30. GTR Alone Versus Control/Placebo/OFD
 Cochrane Database of Systematic Reviews 2006 by Needleman et al.
and edited and published in 2012 with no change in conclusion
 17 RCTs were included in this review,
 RCTs of at least 12 months duration comparing GTR (with or without graft
materials) with OFD
 Results
 Reduced probing pocket depth
 Gain in clinical attachment
 Less gingival recession and
 More gain in hard tissue probing at re-entry surgery
30

31. GTR Alone Versus Control/Placebo/OFD
 Several systematic reviews and meta-analyses have reported
greater benefits to GTR than OFD in the treatment of
intrabony defects
Laurell et al. 1998
Cortellini and Tonetti 2000
Needleman et al. 2001, 2005
Murphy and Gunsolley 2003
Aichelmann-Reidy and Reynolds 2008
31

32. Non-bioresorbable vs Bioresorbable Materials
 Clinical improvements associated with GTR were
independent of the type of barrier membrane used
Villar and Cochran 2010
 Meta-analysis of Murphy and Gunsolley (2003) also failed to
demonstrate a significant difference between ePTFE and the
polymeric barriers (P>0.05)
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33. GTR with/without the adjunctive use of Bone grafts
 Allogeneic and alloplastic bone substitutes have been implanted to
support guided tissue regeneration membranes and to “enhance”
periodontal regeneration
Becker and Becker 1999
 Meta-analysis of Murphy and Gunsolley (2003) did not reveal any
difference in CAL gain between test (barrier in addition to a particulate
graft material) and control (barrier alone) groups
33

34.  In animal models combined therapy (i.e., graft + GTR)
resulted in clinically and histologically superior results
Sculean et al. (2008)
 compared with the single therapies
Kim et al. 1998b
Blumenthal et al. 2003
34

35.  Incorporation of bone grafts enhances clinical attachment and
vertical bone gain in one-wall intrabony defects treated with
barrier membranes,
 while regeneration outcomes obtained from GTR treatment of
two-walled and combined one-, two-, and three-walled
intrabony defects are not enhanced by the addition of grafting
materials
Villar and Cochran (2010)
35

36. Root-Conditioning Agents in Conjunction with
GTR
 There is no evidence that root biomodification enhances
periodontal regeneration in humans
Mariotti 2003
Handelsman et al. 1991
Kersten et al. 1992
36

37. Long-Term Evaluation
 Results of GTR are stable over long periods of time
Nickles et al. 2009
Pretzl et al. 2008
Eickholz et al. 2007, 2004b
Kim et al. 2002
Stavropoulos and Karring 2004
37

38. Wang et al. (2005)
 Barrier-independent
Poor plaque control or premature plaque colonization
Smoking,
Occlusal trauma,
Suboptimal tissue health,
Mechanical habits that interfere with healing,
Inadequate keratinized gingiva,
Improper surgical technique,
Early mechanical insult, and
Loss of wound stability
38

39.  Barrier-dependent
Inadequate root−barrier seal,
nonsterile technique,
instability of the membrane, and premature membrane
exposure/ loss
39

40. Efficacy of GTR in the Treatment
Furcation defects
40

41.  Regeneration of furcation defects has been reported following
a variety of surgical approaches involving
Root surface conditioning, often combined with Coronally
Advanced Flap procedures,
The placement of bone grafts or bone substitute implants or
The use of barrier membranes
Karring and Cortellini 1999
41

42. Therapeutic End Points of Success
 Primary objective - complete elimination of the interradicular defect
 Secondary objective - would be the conversion of a deep furcation
lesion into a shallower one
 Surrogate endpoints will be
 Gains in clinical attachment
 Reduced bleeding on probing,
 Reduced periodontal probing for the evaluation of soft tissue changes
and
 Re-entry bone fill or radiographic bone changes for hard tissue
evaluation
Sanz and Giovanolli 2000
42

43. Class II mandibular furcation
 The results of the meta-analysis performed by Jepsen et al. (2002) of four included
studies (Lekovic et al. 1989, 1991; Wang et al. 1994; Mellonig et al. 1994) that had
addressed the change in horizontal furcation depth outcome showed a statistically
significantly greater reduction in horizontal furcation depth for test groups
compared with open flap debridement
 I and II mandibular molars and buccal and lingual furcations respond equally well
to GTR treatment
 Pontoriero et al. 1988; Machtei et al. 1994
43

44. Class II maxillary furcation
 Sanz and Giovannoli (2000) concluded that the placement of a barrier
membrane does not add any benefit when compared with the OFD
 In contrast, the meta-analysis performed by Jepsen et al. (2002) presented
data that revealed a limited but statistically significant greater reduction in
horizontal furcation depth for test groups compared with open flap
debridement.
44

45.  Evidence indicates that GTR can be successfully used only in the treatment of
class II mandibular furcations and has a limited clinical effect on class II maxillary
furcations
Villar and Cochran 2010
 Significant evidence has demonstrated that treatment of maxillary degree II
furcations and maxillary and mandibular degree III furcation involvements with
GTR is unpredictable
 Guided tissue regeneration procedures in the treatment of furcation defects
demonstrate similar outcomes when different membrane barrier materials were
compared
Sanz and Giovannoli (2000)
(Black et al. 1994; Blumenthal 1993; Bouchard et al.1993, 1997; Caffesse et al. 1997;
Christgau et al. 1995; Garrett et al. 1997; Hugoson et al. 1995; Yukna 1992
45

46.  The use of replacement grafts to improve the results of guided tissue
regenerative therapy is not clearly justified
Sanz and Giovannoli (2000)
Sculean et al. (2008)
 In contrast the results Karring and Cortellini (1999) indicate that an added
benefit may be obtained by the use of grafting materials in combination
with barrier membranes for the treatment of mandibular degree II
furcations.
46

47. Efficacy of GTR in the Treatment
Gingival Recession
47

48. Histological Evidence
 Dogs
Casati et al. 2000; Cortellini et al. 1991; Casati et al. 2000; Lee et al. 2002;
Sallum et al. 2004; Papageorgiou et al. 2009
 Non human primates
Gottlow et al. 1990; Graziani et al. 2005
 human biopsies
Trombelli 1999; Cortellini et al
48

49. space-making solutions
 combination with nonresorbable membranes
 (e.g., titanium-reinforced, gold bar–reinforced, and gold frame–
reinforced membranes)
Kassab et al. 2010
49

50. GTR Versus Mucogingival Surgery
 Subepithelial connective tissue graft protocol provides
improved root coverage and increased keratinized gingiva
over that observed following GTR.
Danesh-Meyer and Wikesjö (2001)
50

51. Percentages of cases with complete root
coverage
 GTR with non-resorbable membranes 46.7% sites
Jepsen et al. 1998
 GTR with resorbable membranes 41.6% sites
Roccuzzo et al. 1996
 Connective tissue graft 83.3% sites
Tatakis and Trombelli 2000
 Free gingival graft 44.4% sites
Borghetti and Gardella 1990
 Coronally advanced flap (with enamel matrix derivative) 64% sites
Modica et al. 2000
51

52. Non-absorbable Versus
Absorbable Membranes
 Absorbable membranes had a higher percentage of complete root coverage
compared to non absorbable membranes.
 The second surgical procedure may disrupt any regenerated tissues
Al-Hamdan et al. (2003); Chambrone et al. (2010)
 The percentage of complete root coverage varied from 33.3% (Dodge et al. 2000)
to 53.3% (Paolantonio et al. 2002) for GTR bioabsorbable membranes, and
 28.0% (Zucchelli et al. 1998) to 41.6% (Roccuzzo et al. 1996) for GTR non-
resorbable membranes.
Chambrone et al. (2010)
52

53. Effect of Root Conditioning on GTR Root
Coverage
 The root surface conditioned group had a higher percentage
of complete root coverage than sites treated without root
conditioning agents
Al-Hamdan et al. 2003
53

54. Effect of Bone Replacement Graft on
GTR Root Coverage
 The addition of bone replacement graft did not improve the
percentage of root coverage
Al-Hamdan et al. 2003; Chambrone et al. 2010
54

55. Non Resorbable Barriers
 Millipore filter
 Rubber dam
Cortellini and Prato 1994; Salama 1994; Paolantonio et al. 1998; Apinhasmit et al.
2002
 Resin−ionomer barrier
Abitbol et al. 1995, 1996; Santi et al. 1997; Tatakis et al. 1999
 Composite nonabsorbable devices (Biobrane)
Aukhil et al. 1986
 Expanded polytetrafluoroethylene (e-PTFE)
Caffesee et al. 1997; Cortellini et al. 1995a; Kilic et al. 1997; Kim et al. 2002;
Paolantonio et al. 1998; Silvestri et al. 2000, 2003; Tonetti et al. 1996, Yoshinari et al.
2001; Zucchelli et al. 1999, 2002; Klein et al. 2001
55

56. Resorbable Barriers
 Colética (Colética, Lyon, France)
 Bio-Gide (Geistlich Biomaterials, Wolhusen,
Switzerland)
 Bio-mend (cross-linked bovine type I
collagen)
 Polyglactin 910 knitted mesh such as Vicryl
(Ethicon, Norderstedt, Germany)
 Polylactic acid such as Atrisorb (dl-lactide
polymer, Atrix Laboratories Inc., Fort Collins,
CO); 37% polylactic acid, 63% pyrrolidine
 Polyglycolic acid
 Copolymer of polylactic and polyglycolic acid
such as Resolut XT (Gore and associates
Inc., Flagstaff, AZ)
 Freeze-dried fascia lata
 Laminar bone barrier (Lambone, Pacific
Coast Tissue Bank, Los Angeles, CA) made
from 100- to 300-m thick sheets of
demineralized, freezeddried ethylene oxide
sterilized cortical bone
 Polyhydroxybutyrate (PHB)
 PHB copolymerized with hydroxyvalerate
 PHB copolymerized with hydroxyvalerate
and polyglactin 910
56

57. New Trends in Barrier Development
 Application of specific adhesion molecules and growth factors
 Addition of specific antimicrobial substances (Atrisorb® D FreeFlow ™)
Aurer and Jorgic-Srdjak 2005
57

58. Bone graft and bone graft
substitutes58

59. Autogenous
 Allograft
 Xenograft
 Alloplast
59

60. Ideal characteristics of a bone graft
 Nontoxic, non-antigenic, resistant to infection,
 No root resorption or ankylosis,
 Strong and resilient,
 Easily adaptable, ready and sufficiently available,
 Minimal surgical procedure,
 Stimulate new attachment
Rosenberg and Rose 1998; Nasr et al. 1999
60

61.  Osteoproliferative (osteogenetic), which means that new bone is formed by
bone-forming cells contained in the grafted material.
 Osteoinduction is a process or a set of processes that stimulate the
phenotypic conversion of progenitor cells within the healing wound to those
that can form osseous tissue
 Osteoconduction defines the process that permits osteogenesis when cells
already committed to bone formation are present in a closed environment
Ellegaard et al. (1973, 1974, 1975, 1976),
Nielsen et al. (1980)
Nasr et al. 1999
61

62. Autogenous grafts
Gold standard by which other grafting materials are compared
Rosenberg and Rose 1998
62

63. Why a Gold standard?
1. Includes cells that participate in osteogenesis
2. A tissue reaction is induced without inducing immunological reactions
3. There is a minimal inflammatory reaction
4. There is rapid revascularization around the graft particles and
5. A potential release of growth and differentiation factors within the grafts
Marx 1994; Kim et al. 2005
63

64. Intraoral grafts
 Harvested from
 the maxillary tuberosity,
 edentulous alveolar areas,
 healing bony wound,
 extraction sites and
 mental and retromolar areas
Nasr et al. 1999, Rosenberg and Rose 1998
64

65. Types of Autogenous bone grafts
 Cortical bone chips
Zaner and Yukna 1984
 Osseous coagulum
Robinson 1969; Jacobs and Rosenberg 1984
 Blend of cortical and cancellous intraoral bone
Zaner and Yukna 1984
65

66. Intraoral Autografts
 Use of bone collectors and bone filters sufficient for only small
regenerative procedures
Blay et al. 2003
 Presence of bacterial pathogens
Graziani et al. 2007
66

67. Extraoral Autografts
 Iliac cancellous bone and marrow provide a great osteogenic potential,
being able to induce cementogenesis, bone regeneration and Sharpey’s
fibers reattachment
Rosen et al. 2000
 Osteogeneic effect was suggested that this was responsible for the
induction of root resorption
Ellegaard et al. 1973, 1974
67

68.  In the systematic review by Reynolds et al. (2003), two studies were
included: Froum et al. (1976) and Renvert et al. (1985b).
 Autogenous bone treatment resulted in significantly greater clinical
attachment level gain and bone fill compared to OFD
 Meta-analysis indicate that the treatment may result in periodontal
regeneration, but not predictably.
Trombelli 2005
68

69.  Autogenous graft alone
Dragoo and Sullivan 1973a; Froum et al. 1975a, 1975b, 1976; Hiatt and Schallhorn
1973; Ogawa et al. 1985; Renvert et al. 1985a; Kim et al. 2005
 Combination with GTR
Orsini et al. 2001, 2008; Camelo et al. 2001; Nygaard-Østby et al. 2008, 2010;
Lindfors et al. 2010
 Emdogain
Leung and Jin 2003; Trombelli et al. 2006; Guida et al. 2007; Yilmaz et al. 2010
 Platelet-Rich Plasma
Czuryszkiewicz-Cyrana and Banach 2006
69

70. Allografts
Frozen Iliac Cancellous bone and marrow
Freeze-Dried Bone Allografts (FDBA)
Demineralized Freeze-Dried Bone Allograft (DFDBA).
70

71.  FDBA provides an osteoconductive scaffold
 DFDBA also provides an osteoconductive scaffold.
 In addition, it provides a source of osteoinductive factors.
Therefore, it elicits
 Mesenchymal cell migration, attachment and osteogenesis when
implanted in well-vascularized bone, and
 It induces endochondral bone formation when implanted in tissues that
would otherwise not form bone
Committee on Research, Science and Therapy of the American Academy
of Periodontology 2001
71

72. Processing of FDBA and DFDBA
Soft tissue Stripping
Initial size reduction
Initial cleaning and decontamination
Microbiological treatment
Freezing
Dehydration
Secondary size reduction
72

73. FDBA
Packaging
Terminal Sterilization
DFDBA
De-mineralization
Buffering
Final Rinse
Packaging
Terminal sterilization
73
Holtzclaw et al. 2008

74. FDBA
 Not demineralized,
 Primarily osteoconductive
 Over time, the graft is resorbed and replaced by new bone.
Rosenberg and Rose 1998; Nasr et al. 1999
74

75. DFDBA
 Demineralization exposes bone morphogenetic proteins
within the bone matrix.
 BMP induce cellular differentiation and the formation of bone
through osteoinduction by inducing pleuripotential stem cells
to differentiate into osteoblasts
Mellonig et al. 1992; Nasr et al. 1999
75

76.  Donor variability
 DFDBA from older donors being less likely to have strong bone-
inducing activity
Schwartz et al. 1998a
 The degree of DFDBA demineralization
 Varies between tissue banks and may also affect clinical regeneration.
Herold et al. 2002
76

77. DFDBA and GTR
 Enhances the effect of GTR procedures
Hanes 2007
Chen et al. 1995; Trejo et al. 2000; Lamb et al. 2001; Duval et al. 2000; Wang
et al. 2002; Couri et al. 2002; Bowers et al. 2003; Kimble et al. 2004;
Aichelmann-Reidy et al. 2004; Kothiwale et al. 2009
77

78. DFDBA and EMD
 Addition of enamel matrix derivative (EMD) to may enhance
osteoinduction
Boyan et al. 2000, 2006; Rosen and Reynolds 2002; Gurinsky et al. 2004;
Harris et al. 2007; Hoidal et al. 2008; Aspriello et al. 2010
 EMD provides a bioactive matrix and also delays the rate of resorption of
DFDBA
78

79. DFDBA and Growth factors
 DFDBA particles must be resorbed for the BMP contained within the matrix
to be released. Thus, making it a time release carrier.
Bowers et al. 1991; Danesh- Meyer et al. 2001; Mott et al. 2002;
Markopoulouet al. 2003; Camelo et al. 2003; Papadopoulos et al. 2003;
Nevins et al. 2003a, 2007; Dereka et al. 2006, 2009; ; Markou et al. 2009,
2010.
 The combined use of rhPDGF-BB and P-15 with a graft biomaterial has
shown beneficial effects in intraosseous defects
 Trombelli L et al. 2008
79

80.  Grafton® DBM (Osteotech, Inc. American Association of Tissue Banks),
 Grafton Plus® DBM Paste (Osteotech, Inc. American Association of TissueBanks),
 Osseograft (Advanced Biotech Products (P) Ltd. India),
 Accell ConnexusTM (Accell® technology+DBM particles+reverse phase medium for
optimal handling) (IsoTis Orthobiologics/GenSci Regeneration Technologies),
 Accell® DBM100® (Accell® technology+DBM particles in putty) (IsoTis Orthobiologics/
GenSci Regeneration Technologies),
 DBX® Demineralized Bone Matrix (Musculoskeletal Transplant Foundation, USA),
 Dynagraft putty (Gen-Sci, Regeneration Laboratories, CA) and
 Osteofil allograft bone paste (Regeneration Technologies, FL)
 Regenafil®, Altiva DBM Paste, BioSetTM, RTI Allograft Paste and Osteofil®
80

81.  No significant differences have been found clinically between FDBA and
DFDBA in primarily intraosseous defects
Piattelli et al. 1996a; Rummelhart et al. 1989; Francis et al. 1995
 In sites where regeneration may be more problematic, DFDBA may be a
more appropriate choice
Committee on Research, Science and Therapy of the American Academy of
Periodontology 2001
 Although minute the risk for disease transmission have raised concerns
with DFDBA.
 In EU countries the commercially available DFDBA is not granted a CE
mark permitting the distribution of the material within the community
81

82. Xenograft
Bovine / Porcine bone and
Natural coral
82

83.  Osteoconductive,
 Readily available and
 Risk free of disease transmission.
 Discovery of bovine spongiform encephalopathy, particularly
in Great Britain
 Religious sentiments in certain countries have limited their
use
Nasr et al. 1999
83

84. Anorganic Bovine-Derived Bone Xenograft
(BDX)
 Deproteinized,
 Sterilized bovine bone with 75–80% porosity and
 Crystal size of approximately 10 µm in the form of cortical
granules
Hürzeler et al. 1997; Piattelli et al. 1999
 Chemical and physical features of BDX is considered identical
to human bone
Berglundh and Lindhe 1997; Piattelli et al. 1999
84

85. BDX vs Autogenous bone
 No donor site is required from the patients;
 Unlimited supply of material;
 The material is easily handled
 The results are predictable
Callan et al. 1993
85

86.  Ridge Augmentation
Callan and Rohrer 1993; Artzi and Nemcovsky 1998; Zitzmann et al. 2001; Kotschy
and Laky 2006; Esposito et al. 2006; Cardaropoli et al. 2005; Lang et al. 2007
 Around endosseous implants
Berglundh and Lindhe 1997; Skoglund et al. 1997; Zitzmann et al. 1997; Hämmerle et
al. 1998; Schlegel and Donath 1998; Juodzbalys and Wang 2007
 Sinus floor elevation procedures
Valentini et al. 1998, 2000; Valentini and Abensur 2003; Piattelli et al. 1999; Hallman
et al. 2001; Wallace and Froum 2003; Orsini et al. 2005; Handschel et al. 2009;
Bornstein et al. 2008; Beloti et al. 2008
 Healing of intrabony peri-implantitis defects
Schou et al. 2003; Schwarz et al. 2006a, 2008, 2009;
Esposito et al. 2008
86

87. 87
 Periradicular surgery in large periapical lesions
Dietrich et al. 2003; Taschieri et al. 2007
 Periodontal bone defects
 Hutchens 1999; Richardson et al. 1999; Scheyer et al. 2002; Scabbia
and Trombelli 2004; Gupta et al. 2007
 in association with membranes
Hutchens 1999; Camelo et al.
1998, 2001; Camargo et al. 2000; Simonpietri-C et al. 2000; Paolantonio et al. 2001;
Pietruska 2001; Paolantonio 2002; Sculean et al. 2003, 2004a, 2005a, 2007b;
Stavropoulos and Karring 2005; Stavropoulos et al. 2003; Stavropoulos et al. 2004;
Vouros et al. 2004; Tonetti et al. 2004; Reddy et al. 2006; Sakata et al. 2006; Liñares et
al. 2006
 In combination with enamel matrix protein derivative
Lekovic et al. 2000; Lekovic et al. 2001; Scheyer et al. 2002; Velasquez-Plata et al.
2002; Zucchelli t al. 2003; Sculean et al. 2002b, 2004b

88.  Bio-Oss® (Osteohealth Co., Shirley, NY),
 Bio-Oss Collagen® (Osteohealth Co., Shirley, NY),
 OsteoGraf/N® (CeraMed Dental, LLC, Lakewood, CO) and
 PepGen P-15® (Dentsply Friadent, Mannheim, Germany)
Sukumar and Drízhal 2008
88

89. Anorganic Porcine-Derived Bone
Xenograft
 OsteoBiol® Gen-Os (Tecnoss Dental, Turin, Italy)
 Augmentation of the alveolar crest and maxillary sinus
Pagliani et al. 2010; Barone et al. 2010
 As a filler in post extraction sockets
Arcuri et al. 2005
 implant treatment
Fernández et al., 2011; Calvo Guirado et al., 2011
89

90. Coralline Calcium Carbonate
 Derived from the exoskeleton of marine madreporic corals
 Structure of the commonly used coral, Porites, is similar to
that of cancellous bone
 Constituents
 Argonite crystals of Calcium carbonate – 97-99%
 Oligoelements – Mg, Na, K, Sr, F, PO4, Amino acids
90

91.  Sr – mineralization and protects calcification
 F – increases osteoblast proliferation
91
Biocoral
Resorbable
Porous
hydroxyapatite
Non-
resorbable

92.  Meta-analysis performed by Trombelli et al. (2002) on four selected
studies (Kim et al. 1996; Mora and Ouhayoun 1995; Schulz et al. 2000;
Yukna 1994a) resulted in a statistically significant difference in CAL gain
between coralline calcium carbonate and OFD
 Bioresorbable calcium carbonate coral implant significantly enhanced
space provision for GTR, while alveolar bone formation appeared to be
enhanced by its use
Wikesjö et al. 2003; Koo et al. 2005; Polimeni et al. 2004
92

93. Alloplasts (Alloplastic Synthetic
Grafts)
Ceramics
Polymers
93

94.  Polymethylmethacrylate and Polyhydroxylethylmethacrylate
(PMMA-PHEMA) Polymers
 Demineralized Dentin Matrix (DDM)
 Hydroxylapatite (HA)
 Calcium Phosphate Cement (CPC)
 β-Tricalcium Phosphate (TCP)
 Calcium Sulfate
 Bioactive Glasses (BG)
 Oily CaOH2 Suspension
 Porous Titanium Granules
94

95.  Microporous and provide added strength to the regenerating
host bone matrix, and permit biological fixation
 Readily available
 Nonallergenic
 Adapt to be effective in a broad range of medical situations
(e.g., cancer, trauma and infective bone destroying diseases)
 Ashman (1992)
95

96. Polymethylmethacrylate and
Polyhydroxylethylmethacrylate
(PMMA-PHEMA) Polymers
Nandi et al (2010)
96
polymers
Natural
Degradable
Non
degradable
Synthetic
Degradable
Non
degradable

97. The properties of PMMA-PHEMA
 Marked hydrophobicity that facilitates hemostasis,
 Extensive microporosity (150–350 µm inter pore size, which results in a
20–30% material porosity),
 Biocompatibility,
 An important compressive strength (50,000–60,000 psi) and
 A negative surface charge (−8 to −10 mV), which is believed to impede
development of infection
Ashman 1988
97

98.  Clinical studies have provided evidence for the effectiveness of this
polymeric grafting material
Shahmiri et al. 1992; Yukna 1990, 1994b; Yukna 1994b; Yukna and Yukna
1997; Yukna and Greer 1992; Calongne et al. 2001; Prakash et al. 2010
 Systematic review
Trombelli et al. 2002
98

99. Demineralized Dentin Matrix (DDM)
 Dentin contains bone morphogenetic proteins (BMPs), which promote the
differentiation of mesenchymal stem cells into chondrocytes, and thus
enhance bone formation.
Reddi and Huggins 1973; Inoue et al. 1986a, 1986b; Ihoki 1991; Muramatsu
et al. 1993; Beertsen et al. 1993; Ymane et al. 1998; Gomes et al. 2001;
Carvalho et al. 2004; Machado et al. 2006; Yagihashi et al. 2009
99

100. Hydroxylapatite (HA)
 Synthetic hydroxyapatite Ca10(PO4)6(OH)2 can be found as porous or
nonporous and in ceramic or nonceramic forms
Kuo et al. 2007
 Healing was characterized primarily by formation of a long junctional
epithelium.
Froum et al. 1982; Beckham et al. 1971; Jarcho et al. 1977; de Putter et al.
1983; Sapkos 1986; Stahl and Froum 1987
100

101.  Meta-analysis of controlled clinical studies
(Galgut et al. 1992; Kenney et al. 1985; Mora and Ouhayoun 1995, Yukna et
al. 1998)
Reported by Trombelli et al. (2002)
 Various forms of HA (porous/nonporous) resulted in significantly greater
attachment gain with respect to conventional OFD.
101

102. Calcium Phosphate Cement (CPC)
 Calcium phosphate cements are gaining special interest due to their
biomimetic nature and potential use as controlled release systems.
 The material did not evoke any inflammatory response, but favored new
bone formation comparable with autologous bone grafting
 Aral et al. 2008; Yuan et al. 2000
 This material had been used as a bioabsorbable barrier for guided tissue
regeneration in periodontal defects
 AlGhamdi et al. 2010b
102

103. β-Tricalcium Phosphate (TCP)
 Tricalcium phosphate is a porous calcium phosphate compound
Yamada et al. 2010
 Alpha form is less stable than beta and forms the stiffer material calcium-
deficient hydroxyapatite when mixed with water
Sukumar and Drízhal 2008; TenHuisen and Brown 1998
 TCP support the attachment, proliferation and differentiation of osteoblasts
and mesenchymal cells as well as bone growth
Von Arx et al. 2001; Aybar et al. 2004; Haimi et al. 2009; Jang et al. 2008;
Kamitakahara et al. 2008
103

104. Calcium Sulphate
 Plaster of Paris or Gypsum
 Calcium sulphate resorbs quickly, over a period of 12 weeks, by a process
of dissolution and is substituted by new bone
Bell 1964
 Inexpensive, readily available, easy to sterilize, safe and simple to use,
eliciting little or no macrophagic reaction, does not adversely impact the
cell proliferation kinetics
Winn and Hollinger 2000; Hogset and Bredberg 1986
104

105. Bioactive Glasses (BG)
 Histologically no signs of periodontal regeneration on a previously
diseased root surface were observed
Nevins et al. 2000; Sculean et al. 2005c
 Treatment of intraosseous defects by means of bioactive glass resulted in
an improvement of the bony lesion when compared to the OFD procedure.
Trombelli et al. (2002); Reynolds et al. (2003
105

106. Oily CaOH2 Suspension Osteoinductal®
 Product of lime slaking from quicklime (CaO)
 Results from pilot studies in experimental animals suggest
that it may accelerate bone healing and promote periodontal
regeneration
Ito et al. 2002; Schwarz et al. 2006b
106

107. Porous Titanium Granules
Tigran™ PTG
 microstructural properties, cell viability and proliferation rate compared to
both Straumann Bone Ceramic and Geistlich Bio-Oss
Sabetrasekh et al. 2010
Wohlfahrt et al. 2010b
107

108. At the 1996 American Academy of Periodontology World Workshop, it was
concluded that synthetic graft materials function primarily as defect fillers.
108

109. Composite graft
 Contains osteogenic cells and osteoinductive growth factors along with a
synthetic osteoconductive matrix.
 A competitive alternative to autograft
Giannoudis et al. 2005; De Long et al. 2007
 Autogenous bone and bone substitute recommended a proportion of 1:2
Merkx et al. 2003; Pripatnanont et al. 2009
109

110.  Limited clinical data exist on the use of composite grafts in the treatment of
periodontal defects
Sanders et al. 1983; Sottosanti 1993; Sottosanti 1995; Anson1996; Anson 1998;
Harris 2004; Harris 1998; Orsini et al. 2001; Maragos et al. 2002; Okuda et al.
2005;Orsini et al. 2008
110

111. Graft material
 A range of 125–1,000 µm is acceptable with 250–750 µm most commonly
available for particle size of grafts used in periodontal treatment.
 A minimal pore size of 100 µm is needed between particles to allow
vascularization and bone formation.
Zaner and Yukna 1984; AlGhamdi et al. 2010a
111

112. Criteria for Evaluation of Graft Success for
Periodontal Regeneration
 Biologic acceptability: the graft should not have any side effects or cause
any unwanted tissue reaction.
 Resorbability: the graft should resorb slowly and be replaced by the
patient’s own bone.
 Regeneration: the graft should have evidence of regenerative ability with
formation of new bone, cementum and periodontal ligament fibers.
 Defect fill: the graft should have evidence of bone fill.
 Stability: the outcome of the treatment should be stable at re-evaluation
visits.
AlGhamdi et al. 2010a
112

113. Chemical Root Surface Modifiers113

114. Rationale
 Periodontitis affected root surfaces are known to be hypermineralized and
may be contaminated with periodontal pathogens and endotoxins
Aleo et al. 1974; Adriaens et al. 1988; Mayfield et al. 1998
 Bacterial toxins are not completely eliminated from the root surface
Kepic et al. 1990
 A smear layer is left by mechanical instrumentation, which act as a
physical barrier, inhibiting cell re-attachment and serving as a reservoir for
bacterial growth
Polson et al. 1984; Blomlöf and Lindskog 1995
114

115.  Root surface conditioning
 provides a biocompatible surface for cell attachment,
 cell spreading and matrix deposition,
 improves mechanical interfacial bonding,
Bosshardt and Sculean 2009
115

116.  Various acids have been used
 Citric and Phosphoric acids,
 Ethylenediaminetetraacetic acid (EDTA) and
 Tetracycline hydrochloride
reviewed by Lowenguth and Blieden 1993;
Mariotti 2003; Wang et al. 2005
116

117. Citric Acid
 Experimental studies in dogs showed new connective tissue attachment
Crigger et al. 1978; Nilvéus et al. 1980; Nilvéus and Egelberg 1980; Klinge et
al. 1981
 Human RCTs did not show any statistically significant clinical results
Stahl et al. 1983; Renvert et al. 1985; Moore et al. 1987; Handelsman et al.
1991; Kersten et al. 1992; Fuentes et al. 1993; Lowenguth and Blieden 1993;
Klinge 1996
117

118.  Histologic evaluation in humans
 Evidence of functionally oriented fibrous attachment following citric acid
demineralization.
Albair et al. 1982
 The meta analysis of seven studies
Blomlöf et al. 2000b; Caffesse et al. 1987; Handelsman et al. 1991;
Kersten et al. 1992; Moore et al. 1987; Parodi and Esper 1984; Smith
et al. 1986
 revealed that the application of citric acid to single or multi rooted
teeth with soft or hard tissue grafts, flaps or membranes was found
as effective in improving attachment levels as non acid-treated
controls
Mariotti 2003
118

119. Tetracycline HCl
 Showed higher ability to affect both dentin smear layer removal and tubule
exposure compared to minocycline and doxycycline
Madison and Hokett 1997; Shetty et al. 2008
 Dentin surfaces treated with TTC-HCl may bind fibronectin more easily
than those treated with citric acid
Terranova et al. 1986
 and promotes fibroblast adhesion and growth
Rompen et al. 1999
119

120.  Nine different TTC-HCl concentrations were applied at doses of 10, 25, 50,
75, 100, 125, 150, 200 and 250 mg/mL.
 The concentrations of 50 and 75 mg/ml applied by burnishing were the
most effective
Ishi et al. 2008; Isik et al. 2000
 Minimal differences exist between citric acid and TTC-HCl treatments
Sammons et al. 1994; Dyer et al. 1993; Wang et al. 1993a, b; Claffey et al.
1987
120

121. EDTA
 Low pH conditioners seemed to erode the surfaces to varying degrees
Blomlöf 1996
 Neutral pH calcium chelator - has a higher capacity to selectively expose
collagen fibers in both healthy cementum surfaces and periodontitis-
affected dentin surfaces
 Preserves the vitality of tissues with direct contact, and
 removes hydroxyapatite from the collagenous dentin matrix more
selectively than low pH etching agents
Klinge 1996; Babay 2000
121

122.  Cheng et al. (2007), in a recent systematic review, also confirmed that
clinical outcomes for root coverage do not depend on the use of root
conditioning.
 In summary,
 Human trials with root surface demineralization have yet to show significant
clinical improvement when compared to non-demineralized controls.
 Histologic evidence seems to suggest that new connective tissue attachment
and limited regeneration. However, this histologic healing pattern does not
result in significant improvement in clinical conditions beyond non-
demineralized control sites.
Wang et al. 2005
122

123. Thank you
and
Best of luck
123