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MANDIBULAR RECONSTRUCTION
WITH BMP & PRP

www.indiandentalacademy.com
INDIAN DENTAL ACADEMY
Leader in continuing dental education
www.indiandentalacademy.com

www.indiandentalacademy.com
INTRODUCTION
 Mandibular defects in OMFS are common.
 Mandibular reconstruction in OMFS is a major challenge.
 Gold sta...
DEFINITION OF RECONSTRUCTION :
 Reconstruction refers to the rebuilding or the restoration
of original form and function ...
MANDIBULAR RECONSTRUCTION
a. Immediate
 Inability to detect recurrence
 Increased risk of graft rejection
b. Delayed
 L...
GOALS OF RECONSTRUCTION :

 Restore maxillofacial form
 Maintain quality of tissues
 Maintain oral competence
 Maintai...
RECONSTRUCTION TECHNIQUES :
Free bone grafts

Poor tolerance to infection

‘K’ Wires

Failure rate of 70%

Stainless steel...
Osteomyocutaneous flaps :
 Pec. major flap with 5th and 6th rib
 Trapezius flap with scapular spine
 Sternocleido masto...
LIMITATION OF CONTEMPORARY TECHNIQUES :
 Limited application
 Short supply of graft material
 Risk of disease transmiss...
TISSUE ENGINEERING
Definition :
Construction of a device in the laboratory containing
viable cells and biological mediator...
BONE MORPHOGENIC PROTEIN
History :


Neuhof in 1917 and Huggisn in 1930 demosntrate

“Heterotropic osteogenesis”.
 In 19...
PRINCIPLES OF BONE REGENERATION

 OSTEOINDUCTION
 OSTEOCONDUCTION
 OSTEOGENESIS

www.indiandentalacademy.com
SOURCE OF BMP :
CYTOKINES
PDGF ; TGFb; FGF; IGF
TGFb1 ; TGFb2
BMP
BMP 1 - 15
www.indiandentalacademy.com
BMP

- Present

in high concentration in bone matrix,

osteosarcoma tissue, dentin matrix.
TGFb – Found in high concentrat...
TYPES OF BMP
BMP1 -

Regulatory molecule; activates BMP

BMP2 -

Ectopic bone formation; OI ; present in bone
spleen, live...
STEPS IN OSTEOINDUCTION :
 Chemotaxis of osteoprogenitor cells.
 Synthesis of Type III collagen.
 Differentiation of ch...
FUNCTIONS :
Growth factors

-

Cell to cell interaction in skeletal
tissue.

BMP Type 2

-

a. Acts on immature
osteoproge...
BMP in mandibular reconstruction
 Pleiotropy
 Bone graft
- Cortical, cancellous or both
 Scaffolds ;
-They are the supp...
FORMS OF BMP :
 Bovine BMP – bBMP
 Recombinant human BMP – rhBMP
-‘K. Bessho’ advocates rhBMP due to consistency of safe...
APPLICATION OF BMP :
-

In clinical surgery BMP is applied as a paste.

-

It contains 1mg of purified BMP per cm3.

-

BM...
LIMITATION OF BMP :
- Bone inducing capacity is unpredictable
- Pathologic expression of BMP
(Yashika & Colleagues in CANC...
CLINICAL RESEARCH :
1. Reconstruction of primate mandible with rhBMP2 and
bone marrow.
(Ichiro, Izumi, Shoji)
JOMS, 2001
U...
2. Reconstruction of mandibular defects with autologous
tissue engineered bone.
(Bradford, B. Kaban, Maria)
JOMS, 2004
Uni...
3. Mandibular defects repair by TGFb and IGF1 released
from osteoconductive gel.
(Rachmiel ; Blumenfeld, Liune)
JCFS, 2005...
PLATLET RICH PLASMA
Definition :
PRP is an autologous concentration of human platlets in a
small volume of plasma.
History...
COMPONENTS OF PRP :
 IGF1
 PGDF
 TGF – b
 VEGF
 EGF
 Cell adheshion molecules

www.indiandentalacademy.com
FUNCTIONS :


PGDF

–

Mitosis

of

healing

cells,

angiogenesis,

macrophage activation.
 IGF – Secreted by osteoblast...
PROCUREMENT OF PRP :
 Withdraws 400 – 450ml of whole blood, 50ml per minute
with a speed of 5000 rpm.
 Citrate phosphate...
APPLICATION OF PRP :
 Initiation of clotting process
 PRP is mixed with PCBM
 10 ml of CaCl2 and 10,000 units of topica...
ROLE OF GROWTH FACTRORS IN PRP :
 Stimulation of cellular activity
 Release of PGDF, TGFb and IGF from platlets in the g...
 Life span of platlets in a site is 5 days.
 Aftermath, bone regeneration is by macrophages.
 Phase I Bone :
a. Formed ...
USES OF PRP :
 Accelerated rate of bone formation was demonstrated on
plain radiograph using PRP.
 Rate of bone generati...
CLINICAL RESEARCH :
1. PRP : Evidence to support its use
(Richard E. Marx)
JOMS, 2004
University of Miami
Clinical Contrav...
2. Differential growth factor retention by platlet rich
plasma.
(Rick ; Jenifer, Sidney)
JOMS, 2005
- To evaluate an optim...
3. Effect of PRP with autogeneous bone graft for maxillary
sinus augmentation in a rabbit model
(Kevin ; Jeffry ; Gloria)
...
SUMMARY :
 Tissue engineering methods in bone regeneration is
promising based on the scientific studies carried out in
an...
REFERENCE :
 Tissue engineering – Richard E Marx ; Lynch
 Bone morphogenic protein – Lindholm
 JOMS ; 2001, 2004, 2005
...
Thank you
www.indiandentalacademy.com
Leader in continuing dental education

www.indiandentalacademy.com
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Mandibular reconstruction / oral surgery courses

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The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.


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Transcript of "Mandibular reconstruction / oral surgery courses "

  1. 1. MANDIBULAR RECONSTRUCTION WITH BMP & PRP www.indiandentalacademy.com
  2. 2. INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com www.indiandentalacademy.com
  3. 3. INTRODUCTION  Mandibular defects in OMFS are common.  Mandibular reconstruction in OMFS is a major challenge.  Gold standard for reconstruction  Newer techniques. www.indiandentalacademy.com
  4. 4. DEFINITION OF RECONSTRUCTION :  Reconstruction refers to the rebuilding or the restoration of original form and function that have been lost owing to disease or treatment of disease. CLASSIFICATION OF BONY DEFECTS  Cantor and curtis  HCL classification www.indiandentalacademy.com
  5. 5. MANDIBULAR RECONSTRUCTION a. Immediate  Inability to detect recurrence  Increased risk of graft rejection b. Delayed  Late covering of primary site  Increase in complication  Increased hospital stay  Cost www.indiandentalacademy.com
  6. 6. GOALS OF RECONSTRUCTION :  Restore maxillofacial form  Maintain quality of tissues  Maintain oral competence  Maintain oral cavity function  Achieve coverage of soft tissue defect www.indiandentalacademy.com
  7. 7. RECONSTRUCTION TECHNIQUES : Free bone grafts Poor tolerance to infection ‘K’ Wires Failure rate of 70% Stainless steel intra meduallary pins Scarring & Contracture AO plates Excellent cosmetic result Titanium, Vitallium Good outcome Stainless steel wire mesh Good outcome Allo plast + Free bone grafts Greater potential neovascularization www.indiandentalacademy.com for
  8. 8. Osteomyocutaneous flaps :  Pec. major flap with 5th and 6th rib  Trapezius flap with scapular spine  Sternocleido mastoid flap with clavicle  Latissmus dorsi flap with iliac crest Distraction osteogenesis www.indiandentalacademy.com
  9. 9. LIMITATION OF CONTEMPORARY TECHNIQUES :  Limited application  Short supply of graft material  Risk of disease transmission  Potential morbidity at donor site www.indiandentalacademy.com
  10. 10. TISSUE ENGINEERING Definition : Construction of a device in the laboratory containing viable cells and biological mediators in a synthetic or biologic matrix that could be implanted in patients to facilitate regeneration of particular tissues.  Bone morphogenic protein - BMP  Platlet rich plasma – PRP www.indiandentalacademy.com
  11. 11. BONE MORPHOGENIC PROTEIN History :  Neuhof in 1917 and Huggisn in 1930 demosntrate “Heterotropic osteogenesis”.  In 1965 Urist unveils the concept of auto induction – Ectopic bone formation.  In 1971 the term osteoinduction was coined.  In 1988 Wozney and Colleagues clones morphogeneic protein using recombinant technology. www.indiandentalacademy.com bone
  12. 12. PRINCIPLES OF BONE REGENERATION  OSTEOINDUCTION  OSTEOCONDUCTION  OSTEOGENESIS www.indiandentalacademy.com
  13. 13. SOURCE OF BMP : CYTOKINES PDGF ; TGFb; FGF; IGF TGFb1 ; TGFb2 BMP BMP 1 - 15 www.indiandentalacademy.com
  14. 14. BMP - Present in high concentration in bone matrix, osteosarcoma tissue, dentin matrix. TGFb – Found in high concentration in platlets about 50ng / ml of whole blood, sequestred within platlets. PERIOSTEUM – Source of Osteoprogenitor cells in bone www.indiandentalacademy.com
  15. 15. TYPES OF BMP BMP1 - Regulatory molecule; activates BMP BMP2 - Ectopic bone formation; OI ; present in bone spleen, liver, brain, kidney, heart, placenta. BMP3 - OI ; Present in lung, kidney, brain, interstine. BMP4&5 - OI ; Embryogenesis BMP6 - Not Osteoinductive BMP7 - OI ; Bone differentiation BMP8&9 - OI ; Bone formation BMP 12&13- Inhibition of terminal differentiation of myoblast. www.indiandentalacademy.com
  16. 16. STEPS IN OSTEOINDUCTION :  Chemotaxis of osteoprogenitor cells.  Synthesis of Type III collagen.  Differentiation of chondroblasts.  Conversion of connective tissue into cartilage.  Invasion by capillaries.  Calcification  Synthesis of Type IV collagen  Synthesis of Type I collagen  Ossification www.indiandentalacademy.com
  17. 17. FUNCTIONS : Growth factors - Cell to cell interaction in skeletal tissue. BMP Type 2 - a. Acts on immature osteoprogenitor cells. b. Differentiate them into osteoblasts and chondroblasts for bone formation. TGFb2 - Stimulates proliferation of osteoprogenitor cells and also chemotactically attracts osteoprogenitor cells to sites of bony defects. www.indiandentalacademy.com
  18. 18. BMP in mandibular reconstruction  Pleiotropy  Bone graft - Cortical, cancellous or both  Scaffolds ; -They are the supporting or carrier materials. -They are rigid, solid, gel, paste or injectible fluid. -They can be absorbable, resorbable, osteoconductive or osteoinductive.  Matrix metallo proteinases - Biodegrades matrices and hydrogels. www.indiandentalacademy.com biodegradable,
  19. 19. FORMS OF BMP :  Bovine BMP – bBMP  Recombinant human BMP – rhBMP -‘K. Bessho’ advocates rhBMP due to consistency of safety and quality for clinical application. -rhBMP is not fully characterized -Activity of rhBMP is 1/10th of bBMP. -Synthesis of bBMP is very minimal 10 – 20mg / kg dry bone www.indiandentalacademy.com
  20. 20. APPLICATION OF BMP : - In clinical surgery BMP is applied as a paste. - It contains 1mg of purified BMP per cm3. - BMP action is decreased on sterilization by irradation - BMP is sterilized by defatting via chloroform / ehtanoland freezing to -70º. www.indiandentalacademy.com
  21. 21. LIMITATION OF BMP : - Bone inducing capacity is unpredictable - Pathologic expression of BMP (Yashika & Colleagues in CANCER in 1994) revealed 40% of osteosarcoma or osteoinductive - Osteoblast and fibrohistio cytic types account for highest level of BMP - No evidence to support BMP causes oncogenesis. - Researchers in 10 years of animal studies in rhBMP has reported no evidence of oncogenesis. - In 2004, FDA cancels sanction for use of rhBMP for clinical use in OMFS www.indiandentalacademy.com
  22. 22. CLINICAL RESEARCH : 1. Reconstruction of primate mandible with rhBMP2 and bone marrow. (Ichiro, Izumi, Shoji) JOMS, 2001 University of Japan. - Implantation of bone marrow alone, rhBMP + bone marrow and rhBMP alone in mandible of Japanese Monkey after creating segmental mandibular defects. Carrier – PGLA. - Results : rhBMP + BM > BM > rhBMP. www.indiandentalacademy.com
  23. 23. 2. Reconstruction of mandibular defects with autologous tissue engineered bone. (Bradford, B. Kaban, Maria) JOMS, 2004 University of Boston. - MSC isolated from ilium of porcine were expanded in culture and seaded to PGLA & Scaffolds. Four defects of 2x 2 cm was created and filled with autogeneous graft, only scaffold, empty as control. - Results : Mandibular defects can be successfully regenerated by MSC on polymer scaffold with penetration of bone and vessels. www.indiandentalacademy.com
  24. 24. 3. Mandibular defects repair by TGFb and IGF1 released from osteoconductive gel. (Rachmiel ; Blumenfeld, Liune) JCFS, 2005 University of Japan. - Mandibular defects in rat mandible was filled with TGFb, IGF1, both hydrogel and control and tested after 3rd and 6th weeks - Results : Defects filled with TGFb and TGFb + IGF1 showed greater bone formation with hydrogel scaffold. www.indiandentalacademy.com
  25. 25. PLATLET RICH PLASMA Definition : PRP is an autologous concentration of human platlets in a small volume of plasma. History : 1997– PRP was first introduced in OMFS by Whitman. 1998 – PRP’s role in bone formation with autogeneous bone by Marx et al. www.indiandentalacademy.com
  26. 26. COMPONENTS OF PRP :  IGF1  PGDF  TGF – b  VEGF  EGF  Cell adheshion molecules www.indiandentalacademy.com
  27. 27. FUNCTIONS :  PGDF – Mitosis of healing cells, angiogenesis, macrophage activation.  IGF – Secreted by osteoblast, mytogenic to osteoblast line of cells.  PRP – Increases the number of growth factors in the graft www.indiandentalacademy.com
  28. 28. PROCUREMENT OF PRP :  Withdraws 400 – 450ml of whole blood, 50ml per minute with a speed of 5000 rpm.  Citrate phosphate dextrose 1 : 5 for anticoagulation Layers of PRP  PPP – 200 ml  PRP – 70 ml  RBC – 180 ml  1 to 3 ml of RBC layer is also added to PRP. www.indiandentalacademy.com
  29. 29. APPLICATION OF PRP :  Initiation of clotting process  PRP is mixed with PCBM  10 ml of CaCl2 and 10,000 units of topical bovine thrombin  In 10 ml syringe 6ml of PRP + 1ml of CaCl2 + 1ml of air is added to form a gelatin mass.  A PRP count of 1 million per micro litre is the benchmark for “therapeutic dose of PRP”. www.indiandentalacademy.com
  30. 30. ROLE OF GROWTH FACTRORS IN PRP :  Stimulation of cellular activity  Release of PGDF, TGFb and IGF from platlets in the graft  PDGF stimulates mitogenesis of marrow stem cells.  Angiogenesis of capillary endothelial mitosis. budding by inducing  TGFb activates fibroblast and preosteoblast to initiate mitosis and lay down bone matrix and collagen matrix to support capillary in growth.  By day 3, capilliaries penetrate the graft  By day 14, complete permeation of capillaries takes place www.indiandentalacademy.com
  31. 31.  Life span of platlets in a site is 5 days.  Aftermath, bone regeneration is by macrophages.  Phase I Bone : a. Formed in the first four weeks b. Bone formed is disorganized woven bone c. Little structural integrity present.  Phase II Bone : a. Mature lamellar bone b. Presence of Haversion system c. Presence of structural integrity d. Formation of periosteum and endosteum www.indiandentalacademy.com
  32. 32. USES OF PRP :  Accelerated rate of bone formation was demonstrated on plain radiograph using PRP.  Rate of bone generation is not only faster but also greater, verified by histiodensitometric study. www.indiandentalacademy.com
  33. 33. CLINICAL RESEARCH : 1. PRP : Evidence to support its use (Richard E. Marx) JOMS, 2004 University of Miami Clinical Contraversy - Failures are due to inappropriate sequestration of platlets, less therapeutic platelet level, inappropriate preparation of PRP. - Benefits are continuity defects, sinus lift augmentation grafting, ridge preservation grafting, periodontal / perioimplant defects - Autologous PRP is the safest www.indiandentalacademy.com - PRP does not promote infection, pH is 6.5
  34. 34. 2. Differential growth factor retention by platlet rich plasma. (Rick ; Jenifer, Sidney) JOMS, 2005 - To evaluate an optimal substrate for extended growth factor retention. - PRP + TRAP ; PRP + Bovine thrombin ; PRP + bone substitues. - PRP + bovine thrombin results in large immediate release of growth factors which is lost via interstitium. - PRP + TRAP – release of growth factor at a slow and sustained rate for longer period www.indiandentalacademy.com
  35. 35. 3. Effect of PRP with autogeneous bone graft for maxillary sinus augmentation in a rabbit model (Kevin ; Jeffry ; Gloria) JOMS, 2005 - This study fails to find a direct stimulatory effect of PRP on healing of autogeneous bone graft using static and dynamic histomorphometric analysis. www.indiandentalacademy.com
  36. 36. SUMMARY :  Tissue engineering methods in bone regeneration is promising based on the scientific studies carried out in animals.  The hurdles of large bone reconstruction by tissue engineering has yet to be explored especially in in humans.  With strides of advancement in technology and global research there is little down that reconstruction of bony defect will be a reality. www.indiandentalacademy.com
  37. 37. REFERENCE :  Tissue engineering – Richard E Marx ; Lynch  Bone morphogenic protein – Lindholm  JOMS ; 2001, 2004, 2005  JCFS ; 2005  IJOMS ; 2004 www.indiandentalacademy.com
  38. 38. Thank you www.indiandentalacademy.com Leader in continuing dental education www.indiandentalacademy.com

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