1. TARRSON FAMILY ENDOWED CHAIR IN PERIODONTICS

2. UCLA SCHOOL OF DENTISTRY

3. Presents
Presents
Dr. E. Barrie Kenney Professor & Chairman Section of Periodontics

4. 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

5. Platelet Rich Plasma Gel
Platelet Rich Plasma –PRP
is obtained by sequestering and concentrating platelets by gradient density centrifugation

6. 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.

7. Preparation of Platelet Rich Plasma (P.R.P.)
Harvest System
3i System
Average Platelets in 6 ml
1.5 million
1.2 million
Time for Isolation
15 minutes
20 minutes
Use of general purpose centrifuges
450 ml blood in citrate – phosphate anticoagulant placed in centrifuge at 5,600 rpm to get buffy coat of platelets plus leukocytes
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

8. 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 PDAF Stimulates new blood vessel production

9. 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.

10. Platelet enriched plasma
Autologous thrombin

11. Lekovic V, Camargo PM, Weinlaender M, Vasilic N, Kenney EB
Platelet Rich Plasma plus Bio-Oss plus Biogide versus Platelet Rich Plasma and Bio-Oss
21 Paired Defects
6 Males, 15 Females
9 smokers 12 non-smokers
Mean age 40 years
6 month clinical and re-entry data
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

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

17. Platelet Rich Plasma plus Bio-Oss plus Atrisorb versus Atrisorb alone
18 paired defects
10 males 8 females
6 smokers 12 non-smokers
Mean age 39 years
6 month clinical and re-entry data
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
Atrisorb-Polylactide in n methyl 2 pyrrolidine.

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

19. Clinical and re-entry data at 6 months
Bio-Oss plus Bio-Gide plus Platelet Rich Plasma versus Flap Debridement
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
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

20. Pocket Depth 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

26. Platelet Rich Plasma 23 patients Interproximal defects Mean age 38
9 smokers, 14 non-smokers
Re-entry 6 months
Comparison between
Bio-Oss/Bio-Gide/PRP
and
Bio-Oss/Bio-Gide
Preparing for publication

27. Pocket Depth (mm) NO STATISTICALLY SIGNIFICANT DIFFERENCE 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
NO STATISTICALLY SIGNIFICANT DIFFERENCE

28. HIGHLY PURIFIED RECOMBINANT PLATELET DERIVED GROWTH FACTOR
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

29. 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

30. 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
Vertical
probing
Horizontal
Attachment
Cases
Before
After
gain
0.5mg/ml 8 2 7 4 6 3
1.0mg/ml 5 1

31. .

32. THE END

33. THE END

34. TRI CALCIUM PHOSPHATE
PORES MICRONS
PARTICLES MM.

35. USE OF T. C. P WITH 0. 3 mg/ml P. D. G. F
USE OF T.C.P WITH 0.3 mg/ml P.D.G.F. AND TETRACYCLINE ROOT CONDITIONING.

40. 6 months
post surgery
few re-entries done

46. 1 week post surgery

47. 6 months post surgery

50. THE END

51. THE END

52. Bone Morphogenetic Proteins
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 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.

53. URIST at UCLA first identified BMP in 1965
URIST at UCLA first identified BMP in 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.

54. intramuscular injection into rodents and so initiate osteogenesis.
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.

55. Demineralized Bone Matrix Collagen Resorbable polymers
Carriers:
Demineralized Bone Matrix
Collagen
Resorbable polymers
Calcium phosphate materials
BMPs need carrier to get effective bone initiation.
Ideal carrier still not found.

56. Used human BMP (osteogenin) Collaplug and DFDBA, in humans
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 al
J Periodontol. 1991, 62:690

57. 50 Non-Submerged Defects
New Bone
New Cementum
New Attachment
Collaplug
0.08
0.11
Collaplug + BMP
0.20
0.05
DFDBA
2.48
1.73
1.72
DFDBA + BMP
2.70
2.35
2.33
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

58. --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
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

59. 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.
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

60. 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 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.

61. 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

62. 6 Month Clinical results using DFDBA plus Bovine Derived Protein
25 patients with grade II furcations in lower molars. Five with BMP
Group control DFDBA alone.
Group micrograms per mg of DFDBA
Group micrograms per mg of DFDBA
Group micrograms per mg of DFDB
Group 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
1.5
Horizontal Attachment Level Change
1.9
0.4

63. Highest concentrations of BMP gave best clinical results

69. THE END