TARRSON FAMILY ENDOWED CHAIR IN PERIODONTICS

UCLA SCHOOL OF DENTISTRY

PresentsPresentsDr. E. Barrie KenneyProfessor & ChairmanSection of Periodontics

E. Barrie Kenney B.D.Sc., D.D.S., M.S., F.R.A.C.D.S.

Tarrson Family Endowed Chair in Periodontics.

Professor and Chairman Division of Associated Clinical Specialties UCLA School of Dentistry

Platelet Rich Plasma –PRP

• is obtained by sequestering and concentrating platelets by gradient density centrifugation

Platelet Rich Plasma Gel

Platelet rich plasma gel is an autologous modification of fibrin

glue made by mixing platelets and fibrinogen centrifuged from whole blood with thrombin and calcium

chloride. Increase platelet concentration in wound by more

than 300 percent.

The PRP is then mixed with calcium chloride and bovine thrombin to form clot that binds bone graft material. Bovine thrombin has been used in cardiovascular surgery and there are 32 reported cases of bleeding

disorders due to cross reactivity of bovine factor V causing antibodies to human factor

V. No cases seen in bone grafting use of PRP. Can substitute human recombinant thrombin or patient’s own thrombin separated out in a

separate protocol or extra purified bovine thrombin.

Harvest System 3i System

Average Platelets in 6 ml

1.5 million 1.2 million

Time for Isolation 15 minutes 20 minutes

Preparation of Platelet Rich Plasma (P.R.P.)

Use of general purpose centrifuges

1. 450 ml blood in citrate – phosphate anticoagulant placed in centrifuge at 5,600 rpm to get buffy coat of platelets plus leukocytes

2. Slow centrifugation of buffy coat at 2,400 rpm to obtain 30 ml of platelet rich plasma.

Takes 30 minutes and should be used within 6 hours

PDGF – Group of polypeptides that stimulate protein synthesis in bone and also stimulate bone resorption, stimulates collagen and matrix production and angiogenesis.

TGF betaβ GROUP of at least 3 polypeptides. Stimulates angiogenesis and production of collagen, ground substance, fibronectin. Inhibits osteoclasts and stimulates osteoblasts to divide.

PDEGF Stimulates proliferation of keratinocytes and fibroblasts

PDAFStimulates new blood vessel production

IGF-1Stimulates cartilage growth, bone matrix production and replication of osteogenic stem cells

PF-4Chemoattractant for fibroblasts and PMNS

PRP mainly used in sinus lifts with autogenous bone, DFDBA or bovine

bone. Case reports suggest increased rate of bone formation.

However, in studies by FROUM et al using PRP – Bio-Oss no difference

seen in bone in sinus lifts.

• Platelet enriched plasma• Autologous thrombin

Platelet Rich Plasma plus Bio-Oss plus Biogide versus Platelet Rich Plasma and Bio-Oss

Comparison of Platelet Rich Plasma, Bovine Porous Bone Mineral and Guided Tissue Regeneration versus Platelet Rich Plasma and Bovine Porous Bone Mineral in the treatment of Intrabony defects:

a Re-entry Study

Lekovic V, Camargo PM, Weinlaender M, Vasilic N, Kenney EB

J. Periodontol 2002, 73:198

• 21 Paired Defects• 6 Males, 15 Females• 9 smokers 12 non-smokers• Mean age 40 years• 6 month clinical and re-entry data

Initial 6 Months

PRP+BioOss+ Biogide

7.81 3.62

PRP+BioOss 7.96 3.98

PRP+BioOss+ Biogide

PRP+BioOss

Attachment Gain (mm)

4.12 3.78

Bone Fill (mm)

4.96 4.82

Pocket Depth (in mm)

Platelet Rich Plasma plus Bio-Oss plus Atrisorb versus Atrisorb alone

Platelet Rich Plasma and Bovine Porous Mineral combined with guided tissue regeneration in the treatment of intrabony defects in humans.

Camargo PM, Lekovic V, Weinlaender M, Vasilic N, Madzarevic M, Kenney EB

J Periodont. Res 2002, 37:300

• 18 paired defects• 10 males 8 females• 6 smokers 12 non-smokers• Mean age 39 years• 6 month clinical and re-entry

dataAtrisorb-Polylactide in n methyl 2 pyrrolidine.

Initial 6 Months

PRP+BioOss+ Atrisorb

7.87 2.89

Atrisorb 7.78 4.16

PRP+BioOss+ Atrisorb

Artisorb

Attachment Gain (mm)

4.37 2.62

Bone Fill (mm)

4.78 2.31

Pocket Depth (mm)

Bio-Oss plus Bio-Gide plus Platelet Rich Plasma versus Flap Debridement

A Re-entry study on use of Bovine Porous bone mineral guided tissue regeneration and Platelet Rich Plasma in the treatment of intrabony defects in humans.

Camargo PM, Lekovic V, Weinlaender M, Vasilic N, Madzarevic M, Kenney EB

Int. J. Periodont. Rest. Dent. 2005, 25:49

• 28 Paired Defects

• 12 Females 16 Males

• Mean age 41.0 years

• 12 Smokers 16 Non-smokers

• Clinical and re-entry data at 6 months

Initial 6 Months

Bio-Oss+Bio-Gide+PRP

7.87 2.89

Flap Curettage 7.78 4.16

Bio-Oss+Bio-Gide+PRP

Flap Curettage

Attachment Gain (mm)

4.37 2.62

Bone Fill (mm)

4.78 2.31

Pocket Depth

Platelet Rich Plasma

Comparison between Bio-Oss/Bio-Gide/PRP

andBio-Oss/Bio-Gide

Preparing for publication

• 23 patients• Interproximal defects• Mean age 38• 9 smokers, 14 non-smokers• Re-entry 6 months

Initial 6 Months

Bio-Oss+Bio-Gide+PRP

8.19 3.31

Bio-Oss + Bio-Gide

8.11 3.95

BioOss+Biogide+PRP

BioOss + Biogide

Attachment Gain (mm) 4.38 3.56

Bone Fill (mm)

4.81 3.96

Pocket Depth (mm)

NO STATISTICALLY SIGNIFICANT DIFFERENCE

Control PDGF

Fibroblasts 9.3 ± 2.0 70.8 ± 14.6*Cementoblasts 0.4 ± 0.2 2.5 ± 0.5*

Osteoblasts 0.5 ± 0.2 3.6 ± 0.7*

Perivascular Cells 2.7 ± 0.6 7.2 ± 1.3

Endothelial Cells 0.7 ± 0.2 3.7 ± 1.0

HIGHLY PURIFIED RECOMBINANT PLATELET DERIVED GROWTH FACTOR

Recombinant Human Platelet Derived Graft Factor with DFDBA

Periodontal Regeneration in Human Class II Furcations using Purified

Recombinant Human Platelet Derived Growth Factor – BB (rhPDGF-BB) with

Bone Allograft

Camelo M et alInt J Periodont Rest Dent 2003, 23:213

• 3 mandibular molars, 1 maxillary

• 2 got 0.5mg/ml PDGF+DFDBA

• 2 got 1.0mg/ml PDGF+DFDBA

• 9-month results

• Block sections

Vertical probing Horizontal probing Attachment

Cases Before After Before After gain

0.5mg/ml 8 2 7 4 6

0.5mg/ml 8 3 7 3 4

1.0mg/ml 6 2 5 3 4

1.0mg/ml 5 3 6 4 1

Results at 9 months (in mm)

• Histology shows regeneration coronal to notch• Bone and cementum fill furcas• One case had cementum formed over enamel projection

.

THE END

Bio-Active Molecules

Platelet-Derived Growth Factor (PDGF)

GEM21 SPDGF + Beta Tricalcium Phosphate (ß T.C.P.)

THE END

Platelet-Derived Growth Factorstimulates bone fill and rate

of attachment level gain: results of a large multicenter

randomized clinical trial.

Nevins M, Han TJ et al.J Perio 2005; 76:2205

Eleven centers with 180 subjects

3 groups: (1) ß T.C.P. + 0.3 mg/ml PDGF(2) ß T.C.P. + 1.0 mg/ml PDGF(3) ß T.C.P. + buffer

Included smokers up to 1 pack per day; all got tetracycline root treatment at surgery, a few got re-entry. No pocket data available.

TRI CALCIUM PHOSPHATE

PORES 1-500 MICRONS

PARTICLES 0.25 -1.00 MM.

USE OF T.C.P WITH 0.3 mg/ml P.D.G.F. AND TETRACYCLINE ROOT CONDITIONING.

6 months post surgeryfew re-entries done

1 week post surgery

6 months post surgery

THE END

Clinical Attachment Level Gains Bone Fill at 6 Months (from Radiographs)

3.53.3TCP alone

3.63.5TCP + 1.0 mg/ml PDGF

3.83.8TCP + 0.3 mg/ml PDGF

6

months

3

months

18%TCP alone

34%TCP + 1.0 mg/ml PDGF

57%TCP + 0.3 mg/ml PDGF

THE END

6-Month Pocket Depth Changes (from package insert)

4.2 mm TCP alone

4.3 mm TCP + 1.0 mg/ml PDGF

4.4 mm TCP + 0.3 mg/ml PDGF

Genetically engineered human Bone Morphogenetic Proteins increase the

amount and purity . Osteogenin is another name for B.M. P. Most

osteogenins are bound to a carrier of bovine type I collagen sponge or

other carrier.

First isolated in acid extracts of human bone by URIST in 1965. Are part of

superfamily of 43 transforming growth factor beta group. At least 16 different

proteins isolated. BMP1 not part of superfamily is a procollagen protease. BMPs secreted by osteoblasts induce

formation of osteoprogenitor cells and stimulate new bone formation.

Bone Morphogenetic Proteins

BMPs 2, 4, 5, 6, 7 needed forregulation of osseous tissue and

for repair. Some are more osteoconductive, e.g., BMP2 and

BMP7 more active than BMP5.

URIST at UCLA first identified BMP in 1965.

This native BMP is present in minuteamounts (1mg per kg of bone), so

need large amounts of bone to produce. Therefore, recombinant

BMPs have been developed.

Recombinant BMPs require up to 10 times

more than native BMPs to give the same

osteogenic activity.

BMPs are assayed byintramuscular injection

into rodents and soinitiate osteogenesis.

BMPs need carrier to get effective bone initiation.

Ideal carrier still not found.

Carriers:

• Demineralized Bone Matrix• Collagen• Resorbable polymers• Calcium phosphate materials

Used human BMP (osteogenin) Collaplug and DFDBA, in humans.

Took 36 block sections from 8 subjects with submerged roots and

50 non-submerged defects in 6 patients. Used calculus as a baseline

measurement of regeneration.

Histologic comparison of Regeneration in Human Intrabony defects when Osteogenin is combined with Demineralized Freeze-Dried Bone Allograft with purified bovine collagen.

Bowers G. et alJ Periodontol. 1991, 62:690

36 Submerged DefectsNew Bone

New Cementum

New Attachment

Collaplug 0.08 0.11 0.08

Collaplug + BMP

0.20 0.08 0.05

DFDBA 2.48 1.73 1.72

DFDBA + BMP 2.70 2.35 2.33

50 Non-Submerged Defects

New Bone

New Cementum

New Attachment

Collaplug 0.78 1.26 0.74

Collaplug + BMP

0.70 1.20 0.67

DFDBA 1.32 1.75 1.31

DFDBA + BMP 1.98 2.31 1.92

No significant difference between DFDBA and DFDBA+BMP

*DFDBA+BMP significantly better than all other groups Bowers

Recombined human Bone Morphogenetic Protein-7 in maxillary sinus floor elevation surgery in 3 patients compared to autogenous bone grafts.

Van den Bergh JPA. et alJ. Clinical Periodontol. 2000, 27:627

--1 sinus with BMP-7 had good bone

--1 sinus no bone but cyst like mass

--2 sinuses had small amount of bone insufficient for implants

--All 5 autogenous sinus grafts had good bone

A feasibility study evaluating rhBMP-2 absorbable collagen sponge for maxillary sinus floor augmentation.

Boyne P. et alInt. J. Perio. Res. Dent. 1997, 17:11

•6 patients3 got BMP-7 in collagen in 4 sinus lifts3 got autogenous iliac bone in 5 sinus lifts

At 6 months took out bone cores.

• Got good bone in cores• One patient had mucus retention cyst

on CT at 16 weeks• Got mean bone height increase of 8.51

mm to 15.73 mm– 8 to 11 patients had sufficient bone for

implant placement.– 2 biopsies at 19 weeks had moderate

amount of bone– 10 biopsies at 24 to 27 weeks had

moderate to large amounts of bone.

Collagen sponge bovine type 1 collagen 12 patients with sinus lifts

evaluated with CT scans at 16 weeks and bone biopsies (7 cases) at 14

weeks to 27 weeks.

This Bovine protein extract (Neo osteo,

Sulzer) contained Bone Morphogenetic Proteins 2,

3, 4, 6, 7, 12, 13.

Bovine derived bone protein extract in the treatment of mandibular class II furcations.

Camargo PM, Wolinsky LE, Burgess AJ, Wagner WR, Paluk SF, Kenney EB.Compend. Cont. Edu. Dent. 2002, 23:1023

25 patients with grade II furcations in lower molars. Five with BMP

Group 1 0.00 control DFDBA alone.Group 2 3.13 micrograms per mg of

DFDBAGroup 3 6.25 micrograms per mg of

DFDBAGroup 4 12.50 micrograms per mg of

DFDBGroup 5 25.0 micrograms per mg of

DFDBA

Evaluated at 6 months no re-entry

Control Group 1

Group 2

Group 3

Group 4

Group 5

Pocket Depth Change

1.3 1.0 1.1 1.8 1.7

Vertical Attachment Level Change

0.5 0.8 0.5 1.5 1.5

Horizontal Attachment Level Change

1.9 0.5 0.4 1.1 1.8

6 Month Clinical results using DFDBA plus Bovine Derived Protein

Highest concentrations of BMP

gave best clinical results

THE END