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Dr. E. Barrie Kenney

Professor & Chairman Section 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

Platelet Rich Plasma Gel

is obtained by sequestering and concentrating platelets by gradient density centrifugation

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 patients own thrombin separated out in a separate protocol or extra purified bovine thrombin.

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

Harvest System Average Platelets in 6 ml Time for Isolation

1.5 million

3i System

1.2 million

15 minutes

20 minutes

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

PDAF Stimulates new blood vessel production

IGF-1 Stimulates cartilage growth, bone matrix production and replication of osteogenic stem cells PF-4 Chemoattractant 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

Pocket Depth (in mm)

Initial PRP+BioOss + Biogide PRP+BioOss 7.81 7.96 6 Months 3.62 3.98 Attachment Gain (mm) Bone Fill (mm) PRP+BioOss + Biogide 4.12 4.96 PRP+BioOss 3.78 4.82

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 data
Atrisorb-Polylactide in n methyl 2 pyrrolidine.

Pocket Depth (mm)

Initial PRP+BioOss + Atrisorb Atrisorb 7.87 7.78 6 Months 2.89 4.16 Attachment Gain (mm) Bone Fill (mm) PRP+BioOss + Atrisorb 4.37 4.78 Artisorb 2.62 2.31

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

Pocket Depth
Initial Bio-Oss+ Bio-Gide+PRP Flap Curettage 7.87 7.78 6 Months 2.89 4.16 Attachment Gain (mm) Bone Fill (mm) Bio-Oss+ Bio-Gide+PRP 4.37 4.78 Flap Curettage 2.62 2.31

Platelet Rich Plasma

Comparison between Bio-Oss/Bio-Gide/PRP and Bio-Oss/Bio-Gide Preparing for publication

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

Pocket Depth (mm)

Initial Bio-Oss+ Bio-Gide+PRP Bio-Oss + Bio-Gide 6 Months BioOss+ Biogide+PRP Attachment Gain (mm) Bone Fill (mm) 4.38 4.81 BioOss + Biogide 3.56 3.96





Control Fibroblasts Cementoblasts Osteoblasts Perivascular Cells Endothelial Cells 9.3 2.0 0.4 0.2 0.5 0.2 2.7 0.6 0.7 0.2

PDGF 70.8 14.6* 2.5 0.5* 3.6 0.7* 7.2 1.3 3.7 1.0

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 al Int 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

Results at 9 months (in mm)

Cases 0.5mg/ml
0.5mg/ml Vertical probing Horizontal probing Attachment Before After Before After gain 8 2 7 4 6 8 3 7 3 4







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

Bio-Active Molecules Platelet-Derived Growth Factor (PDGF)


GEM21 S PDGF + Beta Tricalcium Phosphate ( T.C.P.)

Platelet-Derived Growth Factor stimulates bone fill and rate of attachment level gain: THE END 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) T.C.P. + 0.3 mg/ml PDGF (2) T.C.P. + 1.0 mg/ml PDGF (3) 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.



6 months post surgery few re-entries done

1 week post surgery

6 months post surgery

Clinical Attachment Level Gains

3 6 THE ENDmonths months TCP + 0.3 mg/ml PDGF TCP + 1.0 mg/ml PDGF TCP alone 3.8 3.5 3.3 3.8 3.6 3.5

Bone Fill at 6 Months (from Radiographs)

TCP + 0.3 mg/ml PDGF TCP + 1.0 mg/ml PDGF TCP alone 57% 34% 18%

6-Month Pocket Depth Changes (from package insert) TCP + 0.3 mg/ml PDGF THE END TCP + 1.0 mg/ml PDGF TCP alone 4.4 mm 4.3 mm 4.2 mm

Bone Morphogenetic Proteins

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. 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.

URIST at UCLA first identified BMP in 1965. This native BMP is present in minute amounts (1mg per kg of bone), so need large amounts of bone to produce. Therefore, recombinant BMPs have been developed.

BMPs 2, 4, 5, 6, 7 needed for regulation of osseous tissue and for repair. Some are more osteoconductive, e.g., BMP2 and BMP7 more active than BMP5.

Recombinant BMPs require up to 10 times more than native BMPs to give the same osteogenic activity.

BMPs are assayed by intramuscular injection into rodents and so initiate osteogenesis.

BMPs need carrier to get effective bone initiation. Ideal carrier still not found.

Carriers: Demineralized Bone Matrix Collagen Resorbable polymers Calcium phosphate materials

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 al J Periodontol. 1991, 62:690

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.

50 Non-Submerged Defects
New Bone Collaplug Collaplug + BMP DFDBA DFDBA + BMP 0.08 0.20 2.48 2.70 New Cementum 0.11 0.08 1.73 2.35 New Attachment 0.08 0.05 1.72 2.33

36 Submerged Defects
New Bone New Cementum New Attachment

Collaplug + BMP

0.70 1.32 1.98

1.20 1.75 2.31

0.67 1.31 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 al J. 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 al Int. J. Perio. Res. Dent. 1997, 17:11

6 patients 3 got BMP-7 in collagen in 4 sinus lifts 3 got autogenous iliac bone in 5 sinus lifts At 6 months took out bone cores.

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.

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.

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

This Bovine protein extract (Neo osteo, Sulzer) contained Bone Morphogenetic Proteins 2, 3, 4, 6, 7, 12, 13.

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

Group 1 Group 2 Group 3 Group 4 Group 5 0.00 control DFDBA alone. 3.13 micrograms per mg of DFDBA 6.25 micrograms per mg of DFDBA 12.50 micrograms per mg of DFDB 25.0 micrograms per mg of DFDBA

6 Month Clinical results using DFDBA plus Bovine Derived Protein

Control Group Group Group Group Group 1 2 3 4 5 Pocket Depth Change Vertical Attachment Level Change Horizontal Attachment Level Change 1.3 1.0 1.1 1.8 1.7






Evaluated at 6 months no re-entry






Highest concentrations of BMP gave best clinical results