Bio-materialsBio-materials

EFFECTIVE INEFFECTIVE INPERIODONTAL SURGERY PERIODONTAL SURGERY

OR NOT ?????OR NOT ?????

By,By,Dr.P.R.Ganesh MDS (Perio)Dr.P.R.Ganesh MDS (Perio)

Asst.Prof, GDC,ChennaiAsst.Prof, GDC,Chennai

Age Of Google- Patients Age Of Google- Patients are are AS AS informed as we informed as we

are…are…

Our thinking should now be Our thinking should now be Evidence-Based….Evidence-Based….

So we will see the evidences So we will see the evidences available for various bio-available for various bio-

materials…materials…

Critical Appraisal of Publications…

Fast Introduction of Fast Introduction of Basics…Basics…

PERIODONTITIS ? ? ?PERIODONTITIS ? ? ?

Deep intra-osseous defect

PeriodontitisPeriodontitis Inflammatory disease Inflammatory disease Of the Supporting Tissues Of TeethOf the Supporting Tissues Of Teeth resulting in resulting in PROGRESSIVE PROGRESSIVE

DESTRUCTIONDESTRUCTION of the Periodontal of the Periodontal Ligament Ligament

And Alveolar Bone And Alveolar Bone with either Pocket with either Pocket

Formation/RecessionFormation/Recession or both.or both.

Pathogenesis-Pathogenesis-Multifactorial.Multifactorial.

DIAGNOSIS- PROBINGDIAGNOSIS- PROBING

TREATMENTTREATMENT

Arrest The Inflammatory Disease Arrest The Inflammatory Disease Process Process

By By Removal Of The Subgingival Removal Of The Subgingival BiofilmBiofilm

Establish A Local Environment And Establish A Local Environment And MicrofloraMicroflora

Compatible With Periodontal Health.Compatible With Periodontal Health.

Non-Surgical Therapy

Surgical Therapy

Perio Treatment

We Are Here To Discuss We Are Here To Discuss The Surgical Option For The Surgical Option For

Periodontitis TodayPeriodontitis Today

GOALS OF SURGICAL RXGOALS OF SURGICAL RX

Maintain Results

Regenerate the Lost Tissue

Remove Biofilm

Wound Healing- Wound Healing- OutcomesOutcomes

ScarringScarring Repair – long junctional epitheliumRepair – long junctional epithelium Regeneration – New PDL, Regeneration – New PDL,

Cementum, boneCementum, bone

Optimal Outcome Of Treatment- Regenerate

The Periodontium To Its Pre-disease

StateProven by Histological Evidence of

Regeneration –both architecture and function…

To be considered a regenerative

modality, a material or technique must

HISTOLOGICALLY DEMONSTRATE that bone,

cementumand a functional periodontal ligament (A New Attachment

Apparatus) can be formed on a previously diseased

root surface.

Scaling/Root Planing

Flap surgery

Bio-materials:

1. New Cementum

2. New Periodontal Ligament

3. New Bone

World Workshop in Periodontics of theAmerican Academy of Periodontology

(1996)Requirements For A Periodontal Treatment

To Be Considered A Regenerative Procedure :

1. Animal Histological Studies revealing new cementum, periodontal ligament and bone.

2. Human Clinical Trials demonstrating improved clinical probing attachment and bone levels; and

3. Human Histological Studies - demonstrating new cementum, periodontal ligament and bone coronal to the former defect base

End-point Of TreatmentEnd-point Of Treatment

The goal of clinical research is to provide UNEQUIVOCAL EVIDENCE regarding the potential tangible benefits of a treatment.

Periodontal research cannot afford to keep stopping short of this goal

Bio-Materials Vs. Perio Bio-Materials Vs. Perio RegenerationRegeneration

Periodontal Periodontal Regeneration…Regeneration…

GUIDED TISSUE REGENERATION - periodontal regeneration using barrier membranes - in order to avoid the apical migration of epithelium

INDUCED TISSUE REGENERATION - using specific substances able to induce the regenerative process - growth/differentiation factors or enamel matrix derivatives

Guided Periodontal Guided Periodontal RegenerationRegeneration

Generation 1 – GTRGeneration 1 – GTR Generation 2- Bio-materials Generation 2- Bio-materials

like EMD, BMP, PRP….like EMD, BMP, PRP…. Generation 3- Growth Factors, Generation 3- Growth Factors,

Stem Cells, Tissue Stem Cells, Tissue Engineering..Engineering..

Guided Periodontal Guided Periodontal Regeneration-Regeneration-

Many Options available…to Many Options available…to confuse us.confuse us.

Guided Tissue Guided Tissue RegenerationRegeneration

Generation 1Generation 1 – of periodontal – of periodontal Regeneration….Regeneration….

Nyman, Karring et al…Nyman, Karring et al…

Nyman S, Lindhe J, Karring T, Rylander H. New attachment following surgical treatment of human periodontal disease. J Clin Periodontol 1982: 9: 290–296.

GTR - RationaleGTR - Rationale

To use a physical barrier - barrier membrane

To selectively guide cell proliferation And tissue expansion Within tissue compartments

GTR –Barrier Membrane GTR –Barrier Membrane Prevents gingival epithelium and

connective tissue expansion And favors migration of Cells From

The Periodontal Ligament And alveolar bone into the

periodontal defect.

Gingival Epithelium

Connective Tissue

Alveolar Bone

Periodontal Ligament

GTR- Concepts

Melcher AH. On the repair potential of periodontal tissues. J Periodontol 1976: 47: 256–260.

Types of Membranes-Types of Membranes-

Non-Resorbable Non-Resorbable Resorbable - BiodegradableResorbable - Biodegradable

Disadvantages -Non-Disadvantages -Non-ResorbableResorbable

22ndnd Surgery Required Surgery Required Exposure to Oral environmentExposure to Oral environment Bacterial contaminationBacterial contamination Failure of collapse in non-cross-Failure of collapse in non-cross-

linkedlinked

Disadvantages -Disadvantages -ResorbableResorbable

Risk Of Exposure Collapse Into The Defect Area- Bone

Filler Is Needed Technique Is Sensitive And

Technically Demanding. Harmful Degradation Products Of

Synthetic Membranes

GTR- Tough, Technique-GTR- Tough, Technique-Sensitive Procedure…Sensitive Procedure…

GTR- DisadvantagesGTR- Disadvantages

Other postoperative complications 1. swelling,2. erythema, 3. suppuration, 4. sloughing or perforation5. of the flap, 6. membrane exfoliation 7. and postoperative pain have been reported in independent

studies

GTR -Cochrane Systematic Review -16 RCT’s

Increase in attachment gain for GTR over open flap debridement - 0.02 to 3.60 mm/mean difference 1.22 mm, 95%CI [0.8,1.64])

This value is not a valid estimate of effect because the heterogeneity is substantial and statistically significant.

A substantial variation in their results –not consistent.

IAN NEEDLEMAN, RICHARD TUCKER, Periodontology 2000, Vol. 37, 2005, 106–123

GTR -Cochrane Systematic Review -16 RCT’s- by IAN NEEDLEMAN, RICHARD TUCKER, Periodontology

2000, Vol. 37, 2005, 106–123Until CONSISTENT BENEFITS from

GTR can be shown open flap debridement should remain the

control comparison.

Or do GTR and Pray it Or do GTR and Pray it works out well…works out well…

Generation 2Generation 2

Biomaterial for - Biomaterial for - Periodontal Periodontal

Regeneration….Regeneration….

What are Bio-Materials?What are Bio-Materials?

Biologic Mediators - used for

Periodontal And Maxillofacial Regeneration

What are Bio-Materials? What are Bio-Materials?

Partially Purified Protein Mixture From Developing

Teeth.

Or – Morphogens (Growth Factors) – From

Recombinant Technology.

Biomaterials- Biomaterials- EMD/BMP/PRP/PRF…..EMD/BMP/PRP/PRF…..

Ideal Requirements of Ideal Requirements of Bio-materialsBio-materials

Biocompatability, Enhancement Of Clinical Attachment

Levels, Reduction Of Probing Depths And Hard Tissue Fill Of The

Intrabony Defects.

Bio-materials - for Bio-materials - for

PeriodontalPeriodontal RegenerationRegenerationEnamel Matrix Enamel Matrix

DerivativesDerivatives

Bone morphogenetic Bone morphogenetic ProteinsProteins

Platelet Rich Platelet Rich Plasma/Fibrin..Plasma/Fibrin..

EMD- Enamel Matrix Derivative

EMD- Enamel Matrix Derivative (Emdogain)

Themajor (>95%) component of EMD

is AMELOGENINS - Extracellular Matrix Proteins -

purified acid extract ofproteins from pig enamel matrix

Enamel Matrix Enamel Matrix Derivatives…Derivatives…

Releases Bioactive Peptides Stimulation - Local Growth

Factor Secretion And Cytokine Expression

Induces - Regenerative Process- Amelogenin Deposition Precedes Cementum Formation- Recruitment Of Cementoblasts To The Denuded Root-surfaces.

EMD-EMDOGAIN GEL (Straumann)

Enamel Matrix DerivativesEnamel Matrix Derivatives……Systematic Review, 2002- 2002-

Trombelli et al.Trombelli et al. Meta Analysis of Meta Analysis of Froum et al. 2001,

Okuda et al 2000, Pontoriero et al. 1999, Silvestri et al. 2000, Tonetti et al. 2002

Results showed no evidence of an effect of the predictor on difference in CAL gain between EMD/OFD (P 0.81).

Change in PPD- 1.60mm (95% CI: 0.59–2.62)

Trombelli L, Heitz-Mayfield L, Needleman I, Moles D, Scabbia A: A systematic review of graft materials and biological agents for periodontal intraosseous defects. J Clin Periodontol 2002;

EMD-Cochrane Database of Systematic Reviews, 2009-

Esposito M et al. et al. Thirteen trials  - EMD significantly Thirteen trials  - EMD significantly

improved PAL levels (1.1 mm) and improved PAL levels (1.1 mm) and PPD reduction (0.9 mm) PPD reduction (0.9 mm)

High degree of heterogeneity ( ???)High degree of heterogeneity ( ???) Sensitivity analysis indicated that the Sensitivity analysis indicated that the

overall treatment effect might be overall treatment effect might be overestimated overestimated

The actual clinical advantages of The actual clinical advantages of using EMD are unknown. using EMD are unknown.

Evidence-Based Evidence-Based DentistryDentistry (2003)  (2003) 4,4,  Vibeke Baelum and

Rodrigo Lopez EMD is able to significantly improve EMD is able to significantly improve

PAL levels (1.3 mm) and PPD reduction PAL levels (1.3 mm) and PPD reduction (1 mm) compared with flap surgery .(1 mm) compared with flap surgery .

The authors use The authors use absence of statistical absence of statistical significancesignificance to conclude that they were to conclude that they were unable to explain the heterogeneity unable to explain the heterogeneity found between the studies. found between the studies.

The CAL improvements attributable to The CAL improvements attributable to EMD therapy may EMD therapy may not have a great not have a great clinical impactclinical impact.  . 

Clinical Consideration’sClinical Consideration’s

Short - Half-life /Biological degradation of material is a

concern - ???Whether commercial batches of enamel matrix derivative will be

consistent and provide comparable clinical results in all

cases???

EMD- Only Cellular EMD- Only Cellular CementumCementum

Instead of the development of AEFC, a partially mineralized connective

tissue formed that contained many embedded cells, but no extrinsic fibres. This tissue may thus be classified as bone-like or as a

cementum-like tissue-But not Acellular Extrinsic Fiber

cementum

Effects of enamel matrix proteins on tissue formation along the roots of human teeth Dieter D. Bosshardt, Anton Sculean, Niklaus P. Lang J Periodont Res 2005; 40; 158–167. Blackwell Munksgaard 2005

Evidence-Based Evidence-Based DentistryDentistry (2003)  (2003) 4,4,  Vibeke Ba

elum and Rodrigo Lopez

Where patients have Where patients have intrabony defects, is surgery intrabony defects, is surgery

with enamel matrix with enamel matrix derivative more effective derivative more effective than other treatments? than other treatments?

Evidence-Based Evidence-Based DentistryDentistry (2003)  (2003) 4,4,  Vibeke Ba

elum and Rodrigo Lopez

Currently, the evidence Currently, the evidence for a possible benefit of for a possible benefit of EMD in the treatment of EMD in the treatment of

intrabony defects intrabony defects IS IS RATHER WEAK. RATHER WEAK.

No.2 Biomaterial- BMPNo.2 Biomaterial- BMP

Bone morphogenetic

proteinsrecombinant

human BMP-2 (rhBMP-2)-introduced by Sigurdsson

etal in 1997

BONE MORPHOGENETIC PROTEIN TYPE I COLLAGEN

SPONGE(INFUSE; Medtronic Sonfamore Danek,

Memphis,TN, USA)

Commercial Name….

BONE MORPHOGENETIC PROTEINS

A Group Of Regulatory Glycoproteins -That Are

Members Of The Transforming Growth

Factor-beta Superfamily

In periodontal regeneration

Bone Morphogenetic Protein-2 (OP-2)

Bone Morphogenetic Protein-3 (Osteogenin)

And Bone Morphogenetic Protein-7 (OP-1)

BONE MORPHOGENETIC PROTEINS

Recombinant human bone morphogenetic proteins -used for correcting intrabony, supra-alveolar, furcation and fenestration defects.

In supra-alveolar periodontal defects, the gains in bone and cementum were 3.5 mm and 1.6 mm, respectively

Sigurdsson TJ, Wozney JM, Wikesjo UM. Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration. J Periodontol 1995: 66: 131–138.

Disadvantages of BMPDisadvantages of BMP

Histologic analysis revealed periodontal regeneration with areas of ANKYLOSIS – so now restricted to use

around Implants onlyCochran DL, Jones AA, Lilly LC, Lilly LC, Fiorellini JP, Howell H. Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants: 3-year results of study in humans. J Periodontol 2000: 71: 1241–1257

I ask for Regeneration I ask for Regeneration and I get and I get

ANKYLOSIS????ANKYLOSIS????

PLATELET-RICH PLASMA

Source Of GrowthFactors

PRP …..PRP …..

Autologous blood is drawn and separated into three fractions:

1. platelet-poor plasma (fibrin glue or adhesive);

2. platelet- rich plasma; 3. and red blood cells.

It Contains…..It Contains….. Platelets are enriched by 338% in the

platelet-rich plasma preparation. the concentrations of Platelet-derived

Growth Factor -41.1 ng/ml Transforming Growth Factor-beta1 -

45.9 ng ⁄ ml, Insulin-like Growth Factor (traces) Basic Fibroblast Growth Factor-2

(traces)El-Sharkawy H, Kantarci A -Platelet-rich plasma J Periodontol 2007: 78: 661–669

Platelet-rich plasma

Used To Stabilize Graft Materials And Appears To Enhance Early Soft-tissue Healing

Ineffective For Periodontal Regeneration

Dori F, Gera I, Sculean A. Effect of platelet-rich plasma on the healing of intrabony defects treated with an anorganic bovine bone mineral and expanded polytetrafluoroethylene membranes. J Periodontol 2007: 78: 983–990.

Not every Patient is ready Not every Patient is ready for Harvesting their Own for Harvesting their Own

Blood…Blood…

DiscussionDiscussion

Of Of Periodontal Periodontal

RegenerationRegeneration....

Discussion..Discussion..

Proof of principle - many histological studies, mainly performed in animals have provided evidence that various treatment modalities have regenerative potential.

However, human studies comparing regenerative procedures with the standard of care alone as a control are lacking

Vast difference between Vast difference between animal and Human studiesanimal and Human studies

Surgical variables Surgical variables affecting treatment affecting treatment

outcomesoutcomes Selection Of A Specific Flap Design, Location/Morphology Of Bony

Lesion, And Proper Suturing Technique

Periodontal Reconstructive Surgery For Intraosseous Defects Is A Technique Sensitive Procedure

Non-surgical VariablesNon-surgical Variables

Proper MaintenanceProper Maintenance SmokingSmoking

Other Factors to be Other Factors to be considered….considered….

The Complexity Of The Periodontium, -Which Consists Of Four Different Tissues

The Use Of Very High Doses The Ideal Carrier Enormous Costs - In Relation To

Relatively Small And Non-life-threatening Periodontal Disease

Time –out for a review….Time –out for a review….

Points to Ponder…Points to Ponder… Although BMP/EMD -contribute to

regeneration of the fibrous attachment, their use does not guarantee good results.

The newly formed cementum that they produce is almost always cellular

Acellular cementum forms a much stronger bond to dentin than does the cellular type

Formation Of New Acellular Cementum Formation Of New Acellular Cementum Is A Key Process In The Regeneration Of Is A Key Process In The Regeneration Of Lost PeriodontiumLost Periodontium

Are the regenerated

tissues sustainable?For

Regenerated Periodontium, The Confirmatory

Evidence Would Be Long-term Studies Of The

Treated Defects.

Otherwise we would be left Otherwise we would be left with mixed results..with mixed results..

EVIDENCE…….IN/OUT?EVIDENCE…….IN/OUT?

Enamel Matrix Derivatives

Bone Morphogenetic Proteins

Platelet Rich Plasma

Do they result in Regeneration?

Or not?

Is grafting biomaterials Is grafting biomaterials or biological agents or biological agents more effective than more effective than

open-flap debridement open-flap debridement in treating deep in treating deep

intraosseous defects?intraosseous defects?Trombelli L, Heitz-Mayfield L, Trombelli L, Heitz-Mayfield L,

Needleman I, Moles D, Scabbia A.Needleman I, Moles D, Scabbia A.  A A systematic review of graft materials and systematic review of graft materials and

biological agents for periodontal biological agents for periodontal intraosseous defects. J Clin Periodontol intraosseous defects. J Clin Periodontol

2002; 29(Suppl. 3):S117–S1352002; 29(Suppl. 3):S117–S135

26 RCT26 RCT

Most of the included studies Most of the included studies have been of a rather short duration; have been of a rather short duration; have comprised rather few patients; have comprised rather few patients; considerable heterogeneity with considerable heterogeneity with

respect to their design, methods, respect to their design, methods, organisation, outcomes and organisation, outcomes and maintenance-treatment schemes. maintenance-treatment schemes.

Trombelli L, Heitz-Mayfield L, Needleman I, Moles D, Scabbia Trombelli L, Heitz-Mayfield L, Needleman I, Moles D, Scabbia A.A.  A systematic review of graft materials and biological agents for A systematic review of graft materials and biological agents for periodontal intraosseous defects. J Clin Periodontol 2002; 29(Suppl. periodontal intraosseous defects. J Clin Periodontol 2002; 29(Suppl. 3):S117–S1353):S117–S135

Bio-materials/OFDBio-materials/OFDBecause of the significant Because of the significant

heterogeneity in results between heterogeneity in results between studies in most treatment studies in most treatment

groups, general conclusions groups, general conclusions about the clinical benefit of graft about the clinical benefit of graft biomaterials/biologicals - biomaterials/biologicals - Need Need

To Be Interpreted With Caution.To Be Interpreted With Caution. Trombelli L, Heitz-Mayfield L, Needleman I, Trombelli L, Heitz-Mayfield L, Needleman I, Moles D, Scabbia A.Moles D, Scabbia A.  A systematic review of graft A systematic review of graft materials and biological agents for periodontal materials and biological agents for periodontal intraosseous defects. J Clin Periodontol 2002; intraosseous defects. J Clin Periodontol 2002; 29(Suppl. 3):S117–S13529(Suppl. 3):S117–S135

That evidence seems to That evidence seems to be a bit of no-brainer, be a bit of no-brainer,

right?right?

Currently there is Currently there is NO NO EVIDENCEEVIDENCE to support to support the use of these graft the use of these graft

materials and biological materials and biological agents for periodontal agents for periodontal intra-osseous defectsintra-osseous defects. .

Trombelli L, Heitz-Mayfield L, Trombelli L, Heitz-Mayfield L, Needleman I, Moles D, Scabbia A.Needleman I, Moles D, Scabbia A.  A A systematic review of graft materials and systematic review of graft materials and

biological agents for periodontal biological agents for periodontal intraosseous defects. J Clin Periodontol intraosseous defects. J Clin Periodontol

2002; 29(Suppl. 3):S117–S1352002; 29(Suppl. 3):S117–S135

Does StatisticalSignificance Equate To

Clinical Significance ???

We very much rely on statistical

significance rather than clinical significance.

Expert Advice is In-Expert Advice is In-Valuable….Valuable….

Conclusions…Conclusions…

Treatment IsTreatment IsSuccessful……Successful……

Reduction Of Reduction Of Probing Pocket Probing Pocket Depths, Depths,

Maintenance Or Maintenance Or Improvement Of Improvement Of Clinical Attachment Clinical Attachment Levels, Levels,

And Reduction In And Reduction In Bleeding On Bleeding On Probing Probing

Periodontal Regeneration-

ARE WE THERE YET?

Clinicians increasingly

demandpredictable and faster treatment modalities

Results should Results should focus onfocus on

Patient-centred outcomes

and evaluationof cost/benefit

ratio.

Conclusions…Conclusions…

Differences In CAL Gain And PPD Reduction Vary Greatly With

RespectTo Different

Biomaterial/BiologicalAgents.

Residual defects still remain.

ResultsResults

These findings question the

evidence for a CONSISTENT AND

CLINICALLYWORTHWHILE

BENEFIT.

ConclusionConclusion

Regenerative Periodontal Therapies To Date Can Only Restore A Fraction Of The Original Tissue Volume In Extent.

Complete Periodontal Restoration May Still Be Regarded As An Illusion

Decision Making..Decision Making..

BENEFITS

OUTCOMES

Vs.

No evidence for use of No evidence for use of Biomaterials…Though I am Biomaterials…Though I am

not Einstein…not Einstein…

Future Directions…Future Directions…

Future research should focus on

developing a clearer understanding

of the variability of clinical outcomes

We are on the way to We are on the way to Periodontal Regeneration..Periodontal Regeneration..

Though there are many Though there are many difficulties ahead…difficulties ahead…

Coming in the Future…Wait for it

Thank you….Thank you….

By,

Dr.P.R.Ganesh