Keywords apexogenesis - direct pulp capping - regenerative endodontics - scaffolds - platelet-rich plasma
Introduction
Platelet-rich fibrin (PRF) has been used in dentistry for more than a decade now. Its application in pediatric dentistry can be vital, but it has not been explored. PRF is an autologous product that contains elevated levels of nonactivated, functional intact platelets within a fibrin matrix that releases a relatively constant concentration of growth factors over a few days. Immediately after drawing blood, it is centrifuged, and PRF is produced. It is vitally used in regeneration of hard tissue such as continued root formation, healing after disimpaction, and healing after soft-tissue damage such as gingival surgeries. The production of PRF is easy but the major concern arises in drawing blood from pediatric patients. PRF's application in pediatric dentistry varies from pulp capping and pulpotomy to apexogenesis and healing of extraction socket. Review of literature on the use of PRF in pediatric dentistry is sparse. Studies using bioactive materials containing host's endogenous growth factors represent a paradigm shift from the conservative clinical approach to more predictable regenerative solutions in dentistry.
Platelet-rich Fibrin
PRF is a bioactive surgical additive material prepared from the centrifuging patient's whole blood, a second-generation platelet concentrate described by Choukroun et al.[1 ] PRF is used to accelerate tissue healing. PRF is a simple and nonexpensive chairside process that results in a resorbable fibrin matrix, supplemented with rich platelets and leukocytes. It provides a rich source of growth factors, which includes platelet-derived growth factors, transforming growth factors, vascular endothelial growth factor, and insulin-like growth factor.[2 ] The growth factors are gradually released during the time of the healing. PRF is used in dentistry due to its unique healing potential.[3 ]
[4 ]
Preparation of PRF
Preparation for PRF production follows a standard protocol, as described by Choukroun et al.[1 ] A total of 5 mL of whole venous blood is drawn with anticoagulant in 10 mL tubes and immediately centrifuged at 3000 rotations per minute (rpm) for 10 minutes. The blood is contacted with the test tube wall during the centrifuging process, leading to the activation of platelets which, in turn, in turn initiate coagulation cascade. The resultant product will consist of three layers ([Fig. 1 ]):
Fig. 1 Platelet-rich fibrin (PRF) in test tube after centrifuging showing platelet-poor plasma, PRF clot, and red blood cells (RBCs).
Platelet-poor plasma.
PRF clot.
Red blood cells (RBCs).
Fibrinogen, which is concentrated on the higher part of the tube, is converted into fibrin by the circulating thrombin, thus the platelet-trapped fibrin clot is formed in the middle, RBCs at the bottom, and acellular plasma at the top. The PRF is then removed from the test tube using surgical tweezers and separated from other layers using sterile scissors. PRF is squeezed between the sterile gauze pads ([Fig. 2 ]) to obtain a membranous film, which can be packed into the tooth for specific procedures.
Fig. 2 Platelet-rich fibrin (PRF) is squeezed between the sterile gauze pads.
Constituents of PRF
Growth factors released from PRF have been cited in [Table 1 ].
Table 1
Growth factor cells present in PRF and their function[5 ]
[6 ]
Cells
Functions
Interleukin 1
Key moderator of inflammation control and stimulates T-helper lymphocytes
Interleukin 6
Activates B lymphocytes, stimulates secretion of antibodies
Interleukin 4
Aids in multiplication and differentiation of activated B lymphocytes. Aids healing by controlling inflammation
Tumor necrosis factor-α
Activates monocytes, stimulates remodeling capacities of fibroblasts
Cytokine vascular endothelial growth factor
Promotes angiogenesis
Platelet-derived growth factors
Maintains migration, multiplication and endurance of mesenchymal cell lineages
Insulin-like growth factor
Cell proliferation arbitrator in apoptosis, employs chemotactic results against human osteoblasts
Transforming growth factor β1
Triggers multiplication of fibroblasts and periodontal ligament cells, amplifies collagen manufacture
Vascular endothelial growth factor
Supports the cohesion of the endothelial cell lining of the blood vessel and stimulates neoangiogenesis throughout the wound healing
Fibroblast growth factor
Controls ectodermal origin cells and demonstrates chemotactic and mitogenic efforts on periodontal ligament fibroblast cells
Abbreviation: PRF, platelet-rich fibrin.
Mechanism of Action
PRF aids in wound healing mainly through the action of growth factors,[5 ]
[6 ]
[7 ]
[8 ]
[9 ]
[10 ] which are present in abundance in it. A flowchart describing the series of action is given in [Fig. 3 ].
Fig. 3 Mechanism of action of platelet-rich fibrin (PRF) in wound healing.
Uses of PRF in Pediatric Dentistry
Uses of PRF in Pediatric Dentistry
As Medicament in Pulpotomy
Patidar et al[11 ] conducted a clinical study evaluating PRF and mineral trioxide aggregate (MTA) as a pulpotomy medicament in primary molars. Clinical evaluation was done at 1-, 3- and 6-monthsintervals to check symptoms of pain, tenderness to percussion, soft-tissue swelling, pathologic mobility, and sinus formation. Radiological evaluation was performed at an interval of 6 months and considered successful if there was no furcal or periapical radiolucency, no canal calcification, and no internal and external resorption. The findings from this study revealed that PRF can be used successfully as an appropriate alternative material in pulpotomy of primary teeth. Manhas et al[12 ] in a clinical study evaluated and compared PRF as pulp dressing material in primary molar pulpotomy. The current study evaluates MTA, PRF + MTA, and PRF + Ca (OH)2 as a pulpotomy medicament in primary molars at 1-, 3-, and 6-months followed by clinical and radiographic assessment. It was concluded that there is a favorable future for PRF in the specialty of deciduous tooth vital pulp therapy.
In Apexogenesis of Young Permanent Teeth
Mittal et al[13 ] evaluated the regenerative ability of PRF and artificial scaffolds in dying incomplete root development of permanent teeth, and observed that PRF and collagen are superior scaffolds to chitosan and placentrex for apexogenesis. Hongbing et al[14 ] conducted a retrospective controlled study and concluded that using PRF as scaffold for revascularization achieved similar results compared with the technique of inducing periapical bleeding with regard to the healing of the periapical lesion, continued root formation and resolution of clinical signs and symptoms.[15 ]
[16 ] A systematic review conducted by Miron et al[17 ] evaluated 7 in vitro, 11 in vivo, and 31 clinical studies. As much as 100% of the in vivo studies and 85.7% of the in vitro studies affirmed a statistically significant superiority for combining PRF with regenerative treatments. As much as 87% clinical studies suggested the use of PRF for the regeneration of tissues and wound healing for various treatment procedures in dentistry.[18 ]
[19 ]
As a Pulp Capping Material
According to Bakshi et al,[20 ] PRF showed promising results when used as a direct pulp capping medicament, compared with MTA. Dou et al[21 ] conducted a study to investigate the effect of Ca(OH)2 , MTA, iRoot BP, PRF and concentrated growth factors (CGF) on the proliferation, viability, apoptosis, and mineralization of human dental pulp cells and concluded that PRF and CGF are potential pulp-capping materials for vital pulp therapy. However, further studies on the potency of PRF and CGF as vital pulp-capping material and in vivo studies are necessary.[22 ]
[23 ]
[24 ]
[25 ]
For Surgical or Extraction Wound Closure
PRF is a well-known to have wound healing and regenerative properties, which can used to enhance the healing of surgical wound after cyst or any other defect that causes a large amount of bone loss. In such cases, PRF can be mixed with bone graft and can be packed to the surgical site, in order to enhance healing in children ([Fig. 4 ]).[26 ]
[27 ]
[28 ]
[29 ]
Fig. 4 Platelet-rich fibrin mixed with bone graft ready for loading in surgical site.
Limitation of PRF in Pediatric Dentistry
Limitation of PRF in Pediatric Dentistry
PRF cannot be used to fill large defects in case of cysts. Since autologous blood sample is used to obtain PRF, the quantities produced are low.[30 ]
[31 ]
Allogenic graft tissue is impractical, since PRF membranes are highly specific to the donor.[32 ]
[33 ]
Preserving PRF is not feasible, as it will result in shrinkage due to dehydration and modification of the structural integrity as well as reduced growth factor content in PRF.[34 ]
Advantages of PRF
No biological handling of blood.
Simplified and cost-effective process.
Anticoagulants not required.
Favorable healing due to slow polymerization.
More efficient cell migration and proliferation.
PRF has supportive effect on immune system.
Disadvantages of PRF
Amount available is low, because of autologous blood.
Quick handling of blood is needed, immediately after collection.
Drawing blood from pediatric patients is the major difficulty encountered in this procedure, since children are generally apprehensive to needles.
Conclusion
This article edifies the application of PRF in pediatric dentistry. PRF has been in use for over a decade in regenerative endodontics with an abundance of literature explaining its effectiveness; however, very less or few studies have been conducted on its use in primary dentition and young permanent teeth. Although PRF is found to be a promising material, there is vital need for clinical studies on the primary dentition to support its use, clinical efficacy, and long-term stability in pediatric patients.