Evaluation of Platelet Rich Fibrin Matrix as Regenerative Material in Intraosseous Defects
Condition: Regenerative Inflammation
MeSH terms: Inflammation
Study type: Interventional
Phase: Phase 3

Summary: 
      Technological advancement has led to the development of concentrated platelets, by means of
      centrifugation, popularly known as Platelet concentrates which seem to be a convenient
      approach to obtain autologous growth factors. Locally delivered platelet concentrates are
      supposed to increase the proliferation of connective tissue progenitors to stimulate
      fibroblast and osteoblast activity and enhance angiogenesis, all of which are fundamental to
      tissue healing and regeneration. Several techniques for platelet concentrates are available,
      each method leading to a different product with different biology and potential use.
      Different platelet concentrates are classified, depending on their leucocyte and fibrin
      content. Conventional platelet rich plasma (PRP), also known as first generation platelet
      concentrate is plasma with a platelet concentration above the normal physiologic levels found
      in blood.

      Platelet Rich Fibrin Matrix (PRFM) is an autologous biologic material created by two step
      centrifugation of whole blood without the use of exogenous thrombin. Platelets isolated,
      remain intact and retain their growth factor compliment. This allows a more effective,
      sustained release of growth factors to the wound site following PRFM application. PRFM
      possesses the ability to enhance tissue repair by isolation, concentration and preservation
      of autologous platelets in a dense scaffold like fibrin matrix. The viable platelets contain
      intrinsic growth factors which are probably released in a desired spatial and temporal manner
      that affect every aspect of soft tissue and osseous healing.

      Very limited studies have been conducted to assess the regenerative potential of this new
      modality i.e. PRFM. This study therefore aims at the evaluation of platelet rich fibrin
      matrix as a potential regenerative material in comparison with open flap debridement in human
      periodontal intraosseous defects.
    

Detailed description: 
      Periodontitis is a chronic inflammatory disease caused by bacterial Plaque, the onset and
      progression of which is modulated by a variety of risk factors such as systemic conditions
      and smoking. It causes pathological alterations of the periodontium, resulting in loss of
      connective tissue attachment to the tooth, apical migration of the junctional epithelium
      along the root surface and loss of supporting alveolar bone. If left untreated, cases of
      periodontal disease can lead to premature tooth loss. However, the complex structure of
      periodontium, which consist of soft connective tissue of gingiva and periodontal ligament, as
      well as the mineralized tissues, cementum and bone, makes periodontal wound healing a unique
      process.

      Although, all the tissues of the periodontium get affected, the crux of the problem of
      chronic periodontal diseases lies in the changes that occur in the bone resulting in
      intraosseous defects of various architecture, the persistence of which even after completion
      of active periodontal treatment may increase the site-specific risk of progression of
      periodontitis.

      The two primary components of periodontal therapy involves, the elimination of the
      periodontal infection by eliminating the pathogenic periodontal microflora which induces
      favourable clinical changes in the periodontium and substantial efforts should be made to
      alter the anatomic defect resulting from active periodontitis.

      The resective surgical approach and mucogingival surgeries (MGS) were the major periodontal
      therapies until the 1970s. However, problems with esthetics, root sensitivity and root caries
      resulting from resective therapy for severe periodontitis were eventually pointed out. Also
      resective procedure was admitted to be a "Repair" and not "Regeneration" which has long been
      the goal of periodontal therapy. The past two decades has seen a radical change in
      periodontal surgery with a shift from resective periodontal surgery to regenerative
      therapies. Also the concept of treatment has changed towards regeneration with a goal of
      regaining natural periodontal apparatus.

      Conventional surgical approaches (e.g., flap debridement) continue to offer time-tested and
      reliable methods to access root surfaces, reduce periodontal pockets and attain improved
      periodontal form/architecture. However, these techniques offer only limited potential to
      recover tissues, destroyed during earlier disease phases.

      Broad ranges of treatment options are available, but only some are regarded as truly
      regenerative procedures. Periodontal regeneration is a complex process which requires an
      orchestrated sequence of biologic events, such as cell migration, adherence, growth, and
      differentiation involving a large number of growth factors and cytokines for its
      regulation.To accelerate clinical translation of the same, there is an ongoing need to
      develop therapeutics based on endogenous regenerative technology (ERT), which can stimulate
      latent self-repair mechanisms in patients and harness the host's innate capacity for
      regeneration. ERT in periodontics applies the patient's own regenerative 'tools', that is,
      patient-derived growth factors (GFs) and fibrin scaffolds, to create a material niche in an
      injured site where the progenitor/stem cells from neighbouring tissues can be recruited for
      (in situ) periodontal regeneration.

      Growth factors are naturally occurring proteins that function in the body to promote the
      mitogenesis (proliferation), directed migration and metabolic activity of cells. Numerous
      growth factors have been identified, the expression of which following bone and soft tissue
      injury may regulate the repair and regenerative process. Platelets apart from their role in
      haemostasis have been reported to possess regenerative potential as their alpha granules are
      rich sources of various vital growth factors. These growth factors such as platelet derived
      growth factor, transforming growth factor β1, epithelial growth factor, vascular endothelial
      growth factor, insulin like growth factor and fibroblast growth factor whether used alone or
      in combination have been extensively studied and shown to promote the regeneration of oral
      and maxillofacial bone defects. Platelet growth factors may initiate healing by attracting
      undifferentiated cells within the fibrin matrix that is formed in the very early stages of
      healing process and by triggering cell division.

      Technological advancement has led to the development of concentrated platelets, by means of
      centrifugation, popularly known as Platelet concentrates which seem to be a convenient
      approach to obtain autologous growth factors. Locally delivered platelet concentrates are
      supposed to increase the proliferation of connective tissue progenitors to stimulate
      fibroblast and osteoblast activity and enhance angiogenesis, all of which are fundamental to
      tissue healing and regeneration. Several techniques for platelet concentrates are available,
      each method leading to a different product with different biology and potential use.
      Different platelet concentrates are classified, depending on their leucocyte and fibrin
      content. Conventional platelet rich plasma (PRP), also known as first generation platelet
      concentrate is plasma with a platelet concentration above the normal physiologic levels found
      in blood.

      Currently several methods are available for PRP preparation, most producing a liquid end
      product to promote tissue repair. Due to poor mechanical properties, conventional PRP is
      often difficult to handle in clinical settings that require secure implantation in a specific
      site or where released growth factors could be washed out during an operation. The physical
      properties of PRP can be changed if plasma and platelets are stimulated by the addition of
      calcium chloride and thrombin. The exogenous activation of platelets using bovine thrombin at
      the time of PRP preparation result in an almost immediate degranulation and disintegration of
      platelet granules. Consequently, complete growth factor release will take place at the time
      of PRP preparation and placement. Since wound healing requires a sequential appearance of
      vessels and cells over time, the immediate and almost complete release of platelet granules
      may have very little beneficial effect on later stages of healing.

      In contrast, Platelet Rich Fibrin Matrix (PRFM) is an autologous biologic material created by
      two step centrifugation of whole blood without the use of exogenous thrombin. Platelets
      isolated, remain intact and retain their growth factor compliment. This allows a more
      effective, sustained release of growth factors to the wound site following PRFM application.
      PRFM possesses the ability to enhance tissue repair by isolation, concentration and
      preservation of autologous platelets in a dense scaffold like fibrin matrix. The viable
      platelets contain intrinsic growth factors which are probably released in a desired spatial
      and temporal manner that affect every aspect of soft tissue and osseous healing.

      Very limited studies have been conducted to assess the regenerative potential of this new
      modality i.e. PRFM. This study therefore aims at the evaluation of platelet rich fibrin
      matrix as a potential regenerative material in comparison with open flap debridement in human
      periodontal intraosseous defects.
    

Intervention name(s): Platelet Rich Fibrin Matrix kit; surgical open flap debridement
Intervention type(s): Biological; Procedure
Intervention description(s): Platelet Rich Fibrin Matrix kit was used to procure platelet rich fibrin matrix using centrifugation machine; only surgical open flap debridement was done without use of Platelet Rich Fibrin Matrix kit
Other intervention name(s): centrifugation machine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The patients for this study were selected from the outpatient section of the Department of Periodontics, KLE Society's institute of Dental Sciences, Bangalore, Karnataka. Fifteen patients, aged between 30-55 years (10 males and 5 females) diagnosed with chronic periodontitis, contributing to 30 sites were enrolled for the study by convenience sampling method. It was made clear to the potential subjects that participation was voluntary. Written informed consent was obtained from patients, and ethical clearance for the study was received from the Institutional Ethics Committee (IEC), KLE Society's institute of Dental Sciences, Bangalore. This Randomized controlled trial was carried out from November 2013 to October 2014.
Masking: None (Open Label)
Primary purpose: Treatment