The Effect of Platelet-Rich Fibrin on Bone Defects Repair in Experimental Animals: A Mini-Review

Raafat NS¹* and Abdelkader IB²

¹Department of Pharmacology and Toxicology, The British University in Egypt (BUE), Egypt

²Department of Medical Sciences, The British University in Egypt (BUE), Egypt

*Corresponding author: Shereen Nader Raafat, Department of Pharmacology and Toxicology, Faculty of Dentistry, The British University in Egypt (BUE), Egypt

Received: February 20, 2019; Accepted: March 23, 2019; Published: March 30, 2019

Abstract

Bone is a unique hard form of connective tissue as a result of its heavily calcified extra cellular components. Platelet-Rich Fibrin (PRF), a second generation platelet concentrate, becomes a powerful bioscaffold with an integrated reservoir of growth factors for tissue regeneration. Several studies showed that PRF has positive effect on soft and hard tissue regeneration. Here we present recent literature exploring the osteogenic effects of PRF alone or combined with other materials on bone defects healing in various animal models.

Introduction

Fibrin glue was the first blood-related product used in the surgical field, in the 1980s, and are commonly applied till now topically as hemostatic agent, and to improve wound healing and post-operative motion [1]. In the following years, Transforming Growth Factor β (TGF-β) in the platelets was discovered, and many studies were performed to study its effect on hard and soft tissue healing. In the 1990s, Platelet-Rich Plasma (PRP) began to be used in place of recombinant growth factors, as it is more cost effective than recombinant growth factors and contains higher concentration of platelets than fibrin glue, which resulted in higher benefits [2].

Platelet Rich Fibrin (PRF) was first described by Choukroun et al. (2001), and has been Known as a second generation platelet concentrate. PRF consists of fibrin mesh-work entrapping huge number of platelets, growth factors, and stem cells which acts as a biodegradable scaffold that enhances the development of microvascularization [3] and enables epithelial cell migration towards its surface [4].

The fibrin matrix of PRF is obtained as a result of slow polymerization. This matrix can hold many growth factors such as Platelet-Derived Growth Factors-AB (PDGF-AB), Transforming Growth Factor-β1 (TGF-β1), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), and Insulin-Like Growth Factor-1 (IGF-1), and release them in the wound site gradually throughout prolonged period [5]. The growth factors present in PRF have been shown to promote fibroblast proliferation and accelerate bone repair. In addition, these factors increase tissue vascularity, the rate of collagen formation, and proliferation of mesenchymal stem cells, endothelial cells and osteoblasts. Several authors have also demonstrated that a fibrin matrix provides an optimal support for mesenchymal stem cells, which contribute to bone defects regeneration and of many other tissues [6].

Advantages of Platelet Rich Fibrin (PRF)

Platelet Rich Fibrin (PRF) preparation is easy and reliable, involving simple centrifugation [7]. It is obtained by autologous blood sample [8], unlike fibrin glue, it does not require the addition of external thrombin, and does not cause any immunological reaction [9]. It consists of natural fibrin framework with growth factors within that may keep their activity for a relatively longer period and stimulate tissue regeneration effectively [10]. It can be used as a sole filling materials in bone defects or in combination with bone grafts, depending on the purpose8. It is an economical and quick option compared with recombinant growth factors when used in conjunction with bone grafts [11]. PRF can be used in different forms as gel or as membrane [12]. Finally, studies used PRF reported it to be more efficient and with less controversies on the final clinical results when compared to PRP [7].

This review focused on the most recent researches that investigated the effect of PRF on bone regeneration on experimental animals, either used alone or in combination with other materials. Table 1 summarizes the recent researches involved PRF application including bone defects size and type of animal models, end point of the study, type of examination and the conclusions of the studies.

Table 1: Summary of the most recent researches involved PRF application in bone defects on experimental animals.




  
     
    Animals type and number
    Bone defect place and size
    Materials
    End point
    Examination method
    Study results/conclusion
  
  
    Zhou et al., 2019 [13]
    36 rabbits
    Mandibular defects

      each defect 1.0 x1.0 cm 
     PRF, autologous micro-morselized bone    (autologous), PRF + autologous bone (combined) 
    2, 8, and 12 weeks
     X-ray, electron microscopy, histologic,    Cone-beam computed tomography, dual-energy x-ray absorptiometry.
    In the PRF and autologous bone the    defect area was smaller and filled with osteoporotic trabecular bone. The    bone defect in the combined group showed better repair, increased bone    mineral content, and denser callus than the other groups. PRF enhanced the    effect of the autologous bone.
  
  
    Cihan Dülgeroglu et al., 2019 [14]
    16 Rats
    Femoral fracture

      NA
    platelet-rich fibrin
    4 weeks
    Radiographic and histological    scores
    The results indicated that    platelet rich fibrin is an efficient biomaterial in fracture healing
  
  
    Jeon et al., 2018 [15] 
    24 rabbits
    Cranium

      each defect 15×15mm 
    Gelfoam, Gelfoam + nPRP, and PRF    membrane 
    16 weeks 
    Computed tomography- autopsy,    histological analysis.
    Bone regeneration in the    experimental groups was significantly greater than that in the control group    (Gelfoam), suggesting that PRF might be a therapeutic alternative for bone    grafts.
  
  
    Salih et al., 2018 [16]
    20 rabbits
    Tibia 

      each defect

      1 cm
    PRFM (membrane)
      PRFM + AgNPs (silver    nanoparticles).
    2, 4, 6, and 8 weeks
    Radiographic, histopathological    examination 
    PRF reduced healing time and    brought a faster bone regeneration. Using a combination of PRFM and silver    nanoparticles together gave better acceleration in the bone healing process    than using each one of them separately.
  
  
    Du et al., 2018 [17]
    15 rats 
    Mandible

      each defect

      2 mm x 2 mm
    PRF, PRF+aspirin complex
    12 weeks
    2D/3D μCT, histomorpho-metry.
    Both the PRF and PRF/aspirin    complex enhanced periodontal bone formation. Aspirin could be    sustained-released from PRF/aspirin complex, which caused significand    decrease of inflammation and improve of mesenchymal cells function.
  
  
    Raafat et al., 2018 [18]
    48 rats 
    Tibiae

      each defect

      3mm x 2 mm
    PRF, SIM, and SIM+PRF combined
    4 and 8 weeks
    Histological, immunohisto-chemical,    ELISA, digital X-ray
    PRF enhanced the effect of SIM on    bone regeneration, increased bone metabolic markers expression and enhanced    bone mineral density when used in combination.
  
  
    Horimizu et al., 2017

      [19]
    20 nude mice
    Calvaria

      4 mm in diameter 
    human-cultured alveolar bone-derived    periosteal (hCP)+ (PRF)
    4 weeks 
    μCT, histochemical and    immunohistological 
    Platelet-rich fibrin enhanced new bone formation and local    angiogenesis in the implantation site when combined with hCP.
  
  
    Wang et al., 2017

      [20]
    15 rabbits
    Cranium

      15 mm in diameter
    Mesenchymal Stem Cell (MSC) sheets    with 100 mg nano-hydroxyapatite (nano HA) alone or combined with PRF.
    8 weeks 
     Iconography, histological and    histomorpho-metric 
    Combined application of a MSC    sheet with nano-HA and granular PRF enhanced bone regeneration and could    provide a novel approach for bone tissue regeneration in large bone defects. 
  
  
    Titirinli et al., 2017

      [21]
    10 rabbits
    Mandible 

      diameter of 4.5 mm and depth of 2 mm 
    PRF, APRF (altered PRF)
    8 weeks
    Histological
    PRF and its variations have    positive effects on the new bone tissue and cell number.
  
  
    Popsuishapka et al., 2017 [22]
    18 rabbits
    Vertebra (L3, L4)

      diameter and depth of 3 mm
    Platelet-rich fibrin
    14 days, 1 and 3 months 
    Histological study 
    The introduction of platelet rich    fibrin into the perforated defect of the vertebral body of the rabbits    promoted bone formation 14 days and 1 month after injury.
  
  
    Durmuslar et al., 2016 [23]
    40 diabetic rabbits.
    Calvaria

      Bicortical defect, each 15 mm Calvaria

      Bicortical defect, each 15 mm in diameter 
    Autogenous bone, PRF, autogenous    Autogenous bone, PRF, autogenous bone + PRF combined
    4 weeks and 8 weeks
    μCT, scanning, histological and    histomorpho-metric analysis.
    The amount of bone was highest in    the combination group. PRF can be used safely and caused enhanced bone    healing in diabetic rabbits.
  
  
    Abdullah., 2016 [24]
    45 rats
    Calvaria 

      diameter of 3 mm 
    PRF , PRF+β-TCP combined
    1, 2, 3, 4, and 6 post-operative    weeks
    μCT
    The combination significantly    improved bone regeneration in the first 2 weeks after surgery. No significant    effect was observed after 3, 4, 6 weeks



Table 1: Summary of the most recent researches involved PRF application in bone defects on experimental animals.

Conclusion

Although the limitation of Platelet rich fibrin that it should be used immediately after preparation to prevent contamination, PRF showed promising effect on bone regeneration either alone or combined with other osteogenic materials. Recent studies reported that PRF showed safe and promising results, without contradictory findings, and showed several advantages and possible indications for PRF to be used in the orthopedic field.

Recommendations

Further studies should be conducted to investigate the possibility of formulating PRF, so that it could be preserved for longer period of time before performing operations.

References

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Citation: Raafat NS and Abdelkader IB. The Effect of Platelet-Rich Fibrin on Bone Defects Repair in Experimental Animals: A Mini-Review. Thromb Haemost Res. 2019; 3(1): 1022.

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