April 2000

        Clinical Applications
  Advantages
  Adverse Effects & Limitations
  Difference Between Platelet Gel & Fibrin Glue
  Positive Effects of Platelet Gel
  Cellular Activity
  Bone Resorption
  Bone Formation

Molecular Process 
  "Jump-Start" of Osteogenesis
  Early Consolidation of the Graft
  Speeds Up Mineralization
  Improves Trabecular Bone Density
  Enhances Osteoconduction
  Provides Earlier Availability of Growth Factors and BMP
  What Is Platelet Derived Growth Factor? (PDGF)
  Technique Procurement
  Technique Application
  Cell Separators

AUTOLOGOUS BLOOD/ PLATELET GEL

Platelet gel: An autologous alternative to fibrin glue with applications in oral and maxillofacial surgery.

*Acknowledgement:  The many potential uses for fibrin glue in the field of oral and maxillofacial surgery were first set forth in the English-speaking literature by Matras in 1982.

Platelet gel is prepared by blood collection in the immediate pre-operative period and is processed in the operating suite using a variable-speed autotransfusion/ cell salvage system.

CLINICAL APPLICATIONS

·         Bone grafting for dental implants

·         Sinus lift procedures

·         Sealing perforations of the Schneiderian Membrane

·         Alveolar nerve lateralization procedures

·         Onlay grafts

·         Particulate grafts

·         Alveolar cleft palate repair

·         Oral/nasal fistula repair

·         Oral/antral fistula repair

·         Post-operative hemostasis ileum of bone graft donor sites

·         Continuity defects of the mandible

·         Hemophiliacs which undergo surgery

 

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ADVANTAGES

·         Safety- eliminates risks of clerical errors (no risk of using another patient's blood by mistake)

·         Safety- uses autologous source rather than homologous

·         Convenience for patient- no visit to blood bank necessary

·         Improved support for tissue healing

·         More rapid mineralization of collagen in bone repair and graft sites

·         Earlier stability of grafts

·         More patients are eligible for the procedures because the criteria for blood bank donations does not have to be met

·         Cytokines and growth factors are brought to the site in a manner that would not occur with fibrin glue

·         Formation of a firm nonfriable clot

·         Thrombin causes clevatage of fibrinopeptides A and B from the fibrinogen molecule, which results in the formation of fibrin monomers

·         Thrombin also activates factor XIII that in turn allow for a stable fibrin cross-linkage in the presence of ionized calcium

·         No potential for disease transmission when using autologous blood

·         Less thrombogenic than untreated graft material or grafts pretreated with blood

·         Minimal adhesion formation-resolves in 4-6 months

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ADVERSE EFFECTS & LIMITATIONS

·         Interposition of fibrin glue between opposed nerve bundles has been observed to impede nerve regeneration

·         Does not impede rapid arterial or venous hemorrhage

·         Does not replace good surgical techniques

 

DIFFERENCE BETWEEN PLATELET GEL & FIBRIN GLUE

·         The critical difference is the presence in platelet gel of a high concentration of platelets and a native concentration of fibrinogen

 

POSITIVE EFFECTS OF PLATELET GEL

·         "Jump-starts" the cascade of osteogenesis in a bone graft

·         Promotes early consolidation of the graft

·         Speeds up mineralization of the graft

·         Improves trabecular bone density

·         Allows placement of implants into the graft at an earlier time

·         Provides earlier availability of growth factors and BMP

·         Enhances osteoconduction

 

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CELLULAR ACTIVITY

·         BMP (Bone Morphogenetic Protein) acts as a "switch" that couples bone resorption and bone formation and acts as a modulator of bone activity

 

BONE RESORPTION

·         Bone resorption is initiated by osteoclasts (fused mononuclear cells) that come from the primary vasculature in the fibrin clot of the graft

BONE FORMATION

·         Stem cells in the graft from the original transplantation and stem cells from local tissues and blood vessels respond to growth factors by differentiation into osteoblasts, which starts the cascade of osteogenesis

 

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MOLECULAR PROCESS

"JUMP-START" OF OSTEOGENESIS

·         Because of growth factors are added to the graft at the time of graft replacement (in the platelet gel) instead of being released by the coupled process of resorption and the obligatory replacement, there is an approximate two-month acceleration in the maturation of the bone graft.

 

EARLY CONSOLIDATION OF THE GRAFT

·         The increased amount of Platelet Derived Growth Factor (PDGF) in the graft initiates osteocompetant cell activity at an enhanced molecular rate.

 

SPEEDS UP MINERALIZATION

·         Because mineralization on a graft site is a coupled phenomenon, osteogenesis must proceed according to an A > R > Q > F cycle; where A= Activation; R= Resorption; Q= Quiescence; and F= Formation. Mineralization of the collagen matrix is speeded up due to PDGF being added right from the start in the mineralized bone segment of the graft, instead of being released from collagen as the R phase of the

A > R > Q > F cycle occurs.

 

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IMPROVES TRABECULAR BONE DENSITY

·         There has been reported in the literature a 15% to 30% improvement in trabecular bone density when platelet rich plasma factor is added to the graft.

ALLOWS PLACEMENT OF IMPLANTS INTO THE GRAFTED SITE AT AN EARLIER TIME

ENHANCES OSTEOCONDUCTION

·         Osteoblasts are normally non-motile cells in that they will not normally move across a distance greater than 0.4mm (400 microns).

·         Osteoblasts can be enticed to move across a greater distance by creating a scaffold system (Fibrin) that will assist their movement.

·         As osteoblasts participate in "endocytosis" there is a slow movement of the cell through the fibrin network and osteoid is secreted along its journey.

·         Because PRPF enhances the fibrin network, the movement of osteoblasts along the fibrin network (osteoconduction) is enhanced resulting in the formation of woven bone much earlier than normal.

·         After the osteoblasts make contact with the surface of the implant, they spread out along the surface and begin laying down osteoid. This phase is called osteoconduction. The initial layer is very thin (1-2 microns) and is called a "foot plate". This phase will last three months and at this point the maximum surface area of the implant is covered by bone and no further increase in bone/implant surface area is observed.

·         In a grafted site the percentage of bone/implant contact will be greater than that found in a similar non-grafted site, especially in the maxilla. This enhanced bone/implant contact is assisted by PRPF which enhances the osteoconduction of the graft by releasing PDGF.

·         Platelet Derived Growth Factor (PDGF):

o        PDGF is chemotactic for monocytes and macrophages

o        PDGF is an activator of collagenase in the later stages of wound healing

o        Collagenase allows remodeling of collagen to promote wound strength

o        Tissue Growth Factor Beta 1 (TGFB1) activates fibroblasts to form pro-collagen this results in collagen deposition within the wound

·         Local release of Trombin, Tromboxane A2 and Aenocine Diphosphate

o        Causes intense vasocontriction

o        Enhances hemostatic response

o        Attracts additional platelets to the developing clot.

 

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PROVIDES EARLIER AVAILABILITY OF GROWTH FACTORS AND BMP

When an implant with a roughened surface is inserted into human bone, the initial response is a migration of osteoblasts toward the roughened surface. Electron microscopy has revealed that the interdigitating canaliculi of the osteoblasts actually move along the surface of the implant until they find an acceptable place to rest. These osteoblasts come from the outer surfaces of the trabecular bone and the inner surfaces of the buccal and lingual cortex. The primary response of these osteoblasts is most likely activated by BMP. The additional BMP provided by PRPF in addition to that provided by the initial resorption of bone occurring during the osteophyllic phase (lasts approximately one month) results in earlier maturation of the grafted bone.

 

WHAT IS PLATELET DERIVED GROWTH FACTOR? (PDGF)

·         It is a glycoprotein

·         Molecular weight = 30 Kd

·         Occurs in:

o        Alpha granules of platelets

o        Macrophages

o        Endothelium

·         Appears to be the first growth factor in a wound

·         Initiates connective tissue healing in bone regeneration and bone repair

·         Specific activities:

o        Mitogenesis (increase in cell population of healing cells)

o        Angiogenesis (endothelial mitosis with functional capillaries)

o        Macrophage activation

·         Approximately 0.66ng of PDGF per one million platelets

o        There is 6 X 10-17 grams of PDGF in each platelet

o        There are 1200 molecules of PDGF in each platelet

 

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TECHNIQUE PROCUREMENT

·         When ready for use, the two fluids are rapidly mixed and applied to the wound site, where they form a gel in seconds.

·         Best results occur if the wound is daubed with an absorbent sponge just prior to application.

·         A mixing ratio of seven parts concentrated platelets to one part calcified thrombin (7:1) will provide maximal strength and optimum setting time.

·         The gel thus constituted has the sufficient strength to hold tissue together, but does allow separation and repositioning if required.

·         Any catheter 14 gauge or larger is satisfactory.

·         Sidearm or insertion sheaths can be used.

·         A variety of machines are available that will concentrate the platelet rich plasma.

·         A Site-coupler and syringe can be used to aspirate 10 to 20 ml of PRP from the collection bag and pass the concentrate up to the sterile field.

·         A separate syringe is used to prepare calcified thrombin by dissolving 5000 unite USP bovine thrombin in 5 ml of 10% calcium chloride.

·         The calcified thrombin is passed into the sterile field, taking care that it does not contact the PRP.

 

TECHNIQUE APPLICATION

·         Two syringe technique:

o        Can result in a soft gelatinous mass rather than firm encapsulation. This could be due to incomplete mixing of the components.

o        Blending components in a medicine cup and pouring the syrup-like mixture.

o        Use a 10cc syringe with 7cc of PRP and aspirate 1 ml of calcified thrombin. Quickly tilt the syringe 3-4 times to effect mixing and the gel is rapidly applied to the site.

o        Commercial applicators

o        Double gloving: Rub the gel over the wound to spread evenly, gel will stick to gloves, so double gloving is used.

 

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To research two of the currently used Cell Separators, you may contact:

 

Salvin Dental

Clinaseal Laboratory

CLINASEAL

(800) 535-6566

www.salvin.com

 

Gambro^® BCT^™ ( formerly COBE Cardiovascular (Division of Sorin Biomedica))

14401 W. 65th Way

Arvada, Colorado 80004-3599

(303) 425-5508

(800) 221-7943

www.gambrobct.com

 

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