|Year : 2015 | Volume
| Issue : 2 | Page : 86-90
Platelet concentrates: Bioengineering dentistry's regenerative dreams
Sushma Naag1, Abhishek Savirmath2, Butchi Babu Kalakonda3, Uday Kiran Uppada4, Shekar Kamisetty5, Esther Priyadarshini1
1 Department of Oral and Maxillofacial Pathology, Meghana Institute of Dental Sciences, Nizamabad, Andhra Pradesh, India
2 Department of Prosthodontics, Sri Sai College of Dental Surgery, Vikarabad, Andhra Pradesh, India
3 Department of Periodontics, Sri Sai College of Dental Surgery, Vikarabad, Andhra Pradesh, India
4 Department of Oral and Maxillofacial Surgery, Sri Sai College of Dental Surgery, Vikarabad, Andhra Pradesh, India
5 Department of Endodontics, Sri Sai College of Dental Surgery, Vikarabad, Andhra Pradesh, India
|Date of Web Publication||20-Jul-2015|
Butchi Babu Kalakonda
Department of Periodontics, Sri Sai College of Dental Surgery, Vikarabad, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Technological advances in the fields of medicine and allied sciences had given much needed momentum into the field of molecular biology and regenerative medicine. They indeed provided a boost to innovate new yields for both hard tissue and soft tissue regeneration in dentistry. One among them is the use of platelet concentrates (platelet rich plasma [PRP], platelet rich fibrin [PRF]). Autologous concentrate of blood platelets with a suspension of growth factors offers an enhanced healing of hard and soft tissues. It is an auxiliary benefit for an operator to be aware of platelet concentrates and its healing properties for delivering unsurpassed oral health care to patients. The current article outlines the principles, objectives and clinical insight to the regenerative potential of platelet concentrates in various fields of dentistry. The search words of the PubMed data base were PRF and other permutations of keywords such as "PRP dentistry", PRF dentistry, PRF regenerative dentistry.
Keywords: Platelet rich fibrin, platelet rich plasma, tissue regeneration
|How to cite this article:|
Naag S, Savirmath A, Kalakonda BB, Uppada UK, Kamisetty S, Priyadarshini E. Platelet concentrates: Bioengineering dentistry's regenerative dreams. J Dent Res Rev 2015;2:86-90
|How to cite this URL:|
Naag S, Savirmath A, Kalakonda BB, Uppada UK, Kamisetty S, Priyadarshini E. Platelet concentrates: Bioengineering dentistry's regenerative dreams. J Dent Res Rev [serial online] 2015 [cited 2019 Nov 21];2:86-90. Available from: http://www.jdrr.org/text.asp?2015/2/2/86/161211
| Introduction|| |
Tissue regeneration is a thought provoking area in the field of dentistry. Several materials have been used in the past with varied success. Incorporation of biologically active molecules particularly growth factors have yielded promising results amongst which platelets had been proven to be a good source of these factors.
In addition to its role in regular hemostasis platelets have a wide array of applications which had evinced clinical interest of late in platelet derived products and lead to the evolution of platelet concentrates categorized as first generation platelet concentrates such as platelet rich plasma (PRP) and second generation such as platelet rich fibrin (PRF).
Regenerative potential of platelets was introduced in 1970's and its clinical applications began in the field of medicine in 1980's. From then it took a decade to witness the true potential of platelet derive products in dentistry leading to the evolution of PRP. ,
Platelet rich plasma is essentially an autologous collection of platelets suspended in a small amount of plasma obtained by centrifugation. "PRP" in short, is also synonymous with other terminologies such as autologous platelet gel, plasma rich in growth factors, as well as platelet concentrate. 
Biological rationale for the use of platelet rich plasma
Platelet rich plasma mimics the terminal stage of coagulation cascade, that is, the formation of fibrin clot. The beneficial effects of PRP are through release of certain growth factors released through α granules [Table 1]. 
It promotes collagen synthesis and angiogenesis leading to increased early wound strength.  The growth factors are glycoproteins secreted in response to trauma. These peptides act both locally and systemically in a self regulatory feedback system.  It is proven that PRP "jump starts" the regenerative cascade after trauma leading to quality tissue healing and patient care.  The antimicrobial effect is attributed to high leukocyte concentrate. The risk of disease transmission is almost nullified as the PRP is an autologous blood product. This augments PRP's spectrum of clinical application in head and neck surgery, otolaryngology, burns, cosmetic surgery and dentistry [Figure 1]. 
|Figure 1: Clinical applications of platelet rich plasma in medicine and dentistry|
Click here to view
Platelet rich plasma is distinct from fibrin glue. The glue or sealants are used as surgical adjuncts in promotion of hemostasis at surgical incision sites. The glues can be created from platelet poor plasma (PPP) which primarily comprises of fibrinogen. In contrast PRP has high concentration of platelets along with growth factors which enhances regenerative capacity.  The concentration of these factors tapers by 7 days. The rate of healing is proportional to the number of platelets in the clot within graft/wound and PRP increases that initial platelet number.
Preparation of platelet rich plasma
Many techniques have been advocated for the preoperative preparation of the autologous PRP. However most of them are modifications of the conventional method. The manual protocol popularly known as the Curasan method is the most commonly employed method. 
Blood from a suitable patient is drawn and centrifuged in two spins. The first spin runs for 10 min at 2400 rpm. This separates the red blood cells from plasma. PPP and the PRP with its "buffy coat" is then transferred into a separate tube and then centrifugated for 15 min at 3600 rpm. This gives pure PRP. The resultant product consists of 3 layers: A top layer of PPP; a middle layer, also called "buffy coat" of white blood cells and platelets; and a bottom layer of red blood cells. PRP is the middle layer [Figure 2]. The resultant PRP is mixed with a sterile solution containing 10% calcium chloride and 100U/mL of bovine thrombin and a resultant gel is formed. 
Technological advances in the form of Smart Prep (Harvest Technologies, USA) and the Platelet Concentrate Collection System (3i Implant Innovations, USA) permit preparation of PRP in a clinical set up with ease.
There is a rising debate that PRP causes coagulopathies due to addition of bovine thrombin and adverse reactions such as systemic lupus erythematosus like syndrome and the usage of PRP was considerably reduced.  This has led to evolution of "second generation PRP" coined as PRF which is purely an autologous human thrombin. 
| Platelet Rich Fibrin|| |
Platelet rich fibrin has a unique property of sustained release of important growth factors like platelet derived growth factor (PDGF) and transforming growth factor β (TGF β) along with cytokines for a long period of over 28 days. This ensures a very strong and discrete reparative, regenerative and augmentative process sets in a refined qualitative manner.  The PRF also forms a trimolecular fibrin meshwork which makes it flexible to support cytokine function and cellular migration. ,
Platelet rich fibrin also contains a wide array of growth factors like PDGF, TGF β1, insulin like growth factor, etc., showcasing essential activities such as cell migration, cell attachment, cell proliferation and cell differentiation which play a pivotal role in soft and hard tissue regeneration. 
Why platelet rich fibrin stands out over platelet rich plasma
Platelet rich fibrin offers a better hemostasis and enhances a favorable healing. Minimal risks are involved since there is neither biochemical handling of blood nor the use of any anticoagulants. It offers cell proliferation enhancing regeneration and finally it's a simplified and cost effective process. 
Preparation of platelet rich fibrin
Platelet rich fibrin was first developed in France by Choukroun et al.  Risks associated with the use of bovine thrombin were eliminated with this second generation platelet concentrate.
Platelet rich fibrin preparation is easy and mimics that of PRP. The protocol involves collection of 5-ml of venous blood in two separate 6-ml sterile vacutainer tubes which are not coated with an anticoagulant and centrifuged at 3000 rpm at 400 g for a period of 12 min. 
The resultant product consists of 3 layers: A topmost layer consisting of a cellular PPP, PRF clot in the middle and red blood cells at the bottom. 
The main drawbacks of PRF protocol involve the rapid coagulation of blood initiated on contact with the wall of the test tube due to the absence of an anticoagulant which makes it mandatory to speed up the centrifugation process practically giving less working time for the clinician. Though PRF is used as a gel for regenerative purposes, it can be molded as a membrane by squeezing out the fluids present in the matrix. ,
A recent classification has evolved with emphasis on the platelet concentrates being categorically outlined based on leucocytes and fibrin content [Figure 3]. 
| Clinical Applications of Platelet Rich Fibrin|| |
The various clinical applications of PRF [Table 2] are elaborated below.
Role in periodontal regeneration
To enhance hard and soft tissue healing, PRF was used as a healing biomaterial in implant and periodontal surgical procedures.  PRF also releases TGF and PDGF which promote periodontal regeneration. The fibrin matrix of PRF stimulates neo angiogenesis. PRF also has osteoconductive and osteo inductive properties needed for bone regeneration.  Anilkumar et al. has reported the use of PRF for a novel root coverage procedure for the treatment of gingival recession in the mandibular anterior teeth along with laterally positioned flap technique.  Pradeep et al. conducted a randomized study in three treatment groups comprising of open flap debridement, hydroxyapatite graft and PRF. The study showed a significant bone fill in the PRF group than the control group. Good bone fill along with gain in clinical attachment was seen when PRF was used in addition tohydroxyapatite. 
Role in oral surgery
The effect of PRP on the healing of extraction sockets was evaluated in a study by Alissa et al., the findings of which suggested that the postoperative pain was significantly less with a clinically appreciable soft tissue healing in patients treated with PRP when compared with the control group. There was a statistical significance for sockets only with dense homogenous trabecular pattern as evident by the radiological findings. 
Platelet rich plasma is supposed to increase proliferation of undifferentiated mesenchymal cells and enhance angiogenesis. This forms the biological basis for the clinical benefit of PRP in skeletal reconstructive and preprosthetic surgery. 
It is used as a natural fibrin based biomaterial, favorable to the development of microvascularization and also a guide to epithelial cell migration. This material protects open wounds and enhances healing. PRF contains leucocytes which makes it viable in highly infected wounds. Fibrin also supports immunity by release of CD11/CD18 receptors. The matrix is best used in impacted molar sites, periapical surgeries and preprosthetic surgeries. 
Role in implants
The successful osseointegration of an implant depends on the initial cascade of events and PRP is crucial in enhancing this outcome as PRP when coated on the surface of an implant releases an array of growth factors which enhance the early wound healing providing an initial stabilization for the implant. 
Literature is replete with studies suggesting that implants coated with PRP before placement in to the alveolus had a better osseointegration capability. ,
Studies were conducted on dogs using PRF as sinus augmentation adjunct and suggested simultaneous sinus lift implantation using PRF as a role grafting material was done on animals. 
Role in endodontics
Regenerative endodontics is a versatile field of regenerative medicine. It is a branch that deals with the regeneration of the pulp tissue, damaged root, cervical or apical dentin. The mechanics of revitalization endodontics lies in the ability of the pulp tissue to survive under favorable conditions, to proliferate and aid in regeneration, in spite of tooth being necrotic. The process of revitalization is induced by gentle probing of the pulp canal beyond the periapex tissues.  Necrotic teeth apices have some hertwig's epithelial root sheath which can get proliferated once there is proper asepsis of the canal. , This novel blood clot acts as a template permitting the growth of new tissue into the pulp canal. The above principle was successfully implemented on a 9-year-old boy with an Ellis class IV fracture presenting with an open apex. The role of PRF proved pivotal in the formation of thickened dentinal walls, regression of periapex pathology and apical closure after a 1-year follow-up. 
The use of triple antibiotic paste for canal disinfection along with PRF strengthens the effectiveness of sterilization in carious teeth, infected dentin, periapical lesions and necrotic pulp.  The potential behind success of PRF as a super drug in regenerative endodontics was stressed by Huang et al. who concluded that PRF causes proliferation of human pulp cells and also increases the expression of osteoprotegerin and Alkaline phosphatase activity. 
Jayalaxmietal used PRF with tricalcium phosphate (TCP) bone graft for treating a periapical cyst and concluded that the combined usage of PRF and TCP for bone regeneration has better yielding results than usage of biomaterials alone.  Study done by Keswanietal on the revascularization of immature pulp apices concluded that PRF acts as a biological connector for neoangiogenesis and vascularization. 
Role in pediatric dentistry
Platelet concentrates have made their mark felt in pediatric dentistry also. PRP was found to be much superior to routinely used calcium hydroxide in pulp capping procedure based on the tissue reaction between these materials. Though formocresol had been the cornerstone for pedodontists for a pulpotomy procedure, it has been criticized for its tissue irritating, cytotoxic and mutagenic effects. PRP was found to be an ideal material with low toxic effect and increased tissue regenerating properties showing enhanced clinical results. 
| Conclusion|| |
Platelet concentrates are a novel ingress of tissue engineering to clinicians andresearchers in the field of dentistry. Its inherent ability to harbor growth factors facilitatesstimulation and acceleration of both soft and hard tissue regeneration. Being a completely natural, physiologic, and economical source of autologous product, it possesses beneficial effects of eliminating concerns about immunogenicreactions and disease transmission. However, since knowledge on this topic is still in its preliminary stage, the effectiveness of these platelet concentrates in regenerative procedures should be evaluated in studies comprising of large samples and their clinical applications in randomized control trials has to be encouraged.
| References|| |
Whitman DH, Berry RL, Green DM. Platelet gel: An autologous alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg 1997;55:1294-9.
Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:638-46.
Wang HL, Avila G. Platelet rich plasma: Myth or reality? Eur J Dent 2007;1:192-4.
Smith RG, Gassmann CJ, Campbell MS. Platelet-rich plasma: Properties and clinical applications. J Lanc Gen Hosp 2007;2:73-7.
Tischler M. Platelet rich plasma. The use of autologous growth factors to enhance bone and soft tissue grafts. N Y State Dent J 2002;68:22-4.
Weibrich G, Kleis WK, Hafner G, Hitzler WE, Wagner W. Comparison of platelet, leukocyte, and growth factor levels in point-of-care platelet-enriched plasma, prepared using a modified Curasan kit, with preparations received from a local blood bank. Clin Oral Implants Res 2003;14:357-62.
Shivashankar VY, Johns DA, Vidyanath S, Kumar MR. Platelet rich fibrin in the revitalization of tooth with necrotic pulp and open apex. J Conserv Dent 2012;15:395-8.
Naik B, Karunakar P, Jayadev M, Marshal VR. Role of Platelet rich fibrin in wound healing: A critical review. J Conserv Dent 2013;16:284-93.
Hotwani K, Sharma K. Platelet rich fibrin-A novel acumen into regenerative endodontic therapy. Restor Dent Endod 2014;39:1-6.
Saluja H, Dehane V, Mahindra U. Platelet rich fibrin: A second generation platelet concentrate and a new friend of oral and maxillofacial surgeons. Ann Maxillofac Surg 2011;1:53-7.
Choukroun J, Adda F, Schoeffler C, Vervelle A. Une opportunité en paro-implantologie: Le PRF. Implantodontie 2001;42:55-62.
Vivek G, Vivek KB, Singh GP, Ashish M, Rhythm B. Regenerative potential of platelet rich fibrin in dentistry: Literature review. Asian J Oral Health Allied Sci 2011;1:22-8.
Sunitha Raja V, Munirathnam Naidu E. Platelet-rich fibrin: Evolution of a second-generation platelet concentrate. Indian J Dent Res 2008;19:42-6.
Lauritano D, Avantaggiato A, Candotto V, Zollino I, Carinci F. Is platelet rich fibrin really useful in oral and maxillofacial surgery? Lights and shadows of this new technique. Ann Oral Maxillofac Surg 2013;1:25-9.
Preeja C, Arun S. Platelet rich fibrin: Its role in periodontal regeneration. Saudi J Dent Res 2014;5:117-22.
Anilkumar K, Geetha A, Uma S, Ramakrishnan T, Vijayalakshmi R, Pameela E. Platelet-rich-fibrin: A novel root coverage approach. J Indian Soc Periodontol 2009;13:50-4.
Pradeep AR, Bajaj P, Rao NS, Agarwal E, Naik SB. Platelet rich fibrin combined with porous hydroxyapatite graft for the treatment of three-wall intra bony defects is chronic periodontitis: A randomized controlled clinical trial. J Periodontol 2012;83:1499-507.
Alissa R, Esposito M, Horner K, Oliver R. The influence of platelet-rich plasma on the healing of extraction sockets: An explorative randomised clinical trial. Eur J Oral Implantol 2010;3:121-34.
Schilephake H. Bone growth factors in maxillofacial skeletal reconstruction. Int J Oral Maxillofac Surg 2002;31:469-84.
Albanese A, Licata ME, Polizzi B, Campisi G. Platelet-rich plasma (PRP) in dental and oral surgery: From the wound healing to bone regeneration. Immun Ageing 2013;10:23.
Cabbar F, Güler N, Kürkcü M, Iseri U, Sençift K. The effect of bovine bone graft with or without platelet-rich plasma on maxillary sinus floor augmentation. J Oral Maxillofac Surg 2011;69:2537-47.
Jeong SM, Lee CU, Son JS, Oh JH, Fang Y, Choi BH. Simultaneous sinus lift and implantation using platelet-rich fibrin as sole grafting material. J Craniomaxillofac Surg 2014;42:990-4.
Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: New treatment protocol? J Endod 2004;30:196-200.
Windley W 3 rd
, Teixeira F, Levin L, Sigurdsson A, Trope M. Disinfection of immature teeth with a triple antibiotic paste. J Endod 2005;31:439-43.
Huang FM, Yang SF, Zhao JH, Chang YC. Platelet-rich fibrin increases proliferation and differentiation of human dental pulp cells. J Endod 2010;36:1628-32.
Jayalakshmi KB, Agarwal S, Singh MP, Vishwanath BT, Krishna A, Agrawal R. Platelet-rich fibrin with ß-tricalcium phosphate-A noval approach for bone augmentation in chronic periapical lesion: A case report. Case Rep Dent 2012;2012:902858.
Keswani D, Pandey RK. Revascularization of an immature tooth with a necrotic pulp using platelet-rich fibrin: A case report. Int Endod J 2013;46:1096-104.
Rani S, Iram Z, Shipra J. Platelet rich plasma-A healing aid and perfect enhancement factor: Review and case report. Int J Clin Pediatr Dent 2011;4:69-75.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]