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Journal of Oral Science & Rehabilitation No. 2, 2016

Journal of Oral Science & Rehabilitation 46 Volume 2 | Issue 2/2016 growthfactorsknowntobepresentintheƴ-gra- nules of the platelets in PRP gel samples.26 Results obtained from the present study indi- cate that PRP gel contains the six tested growth factors:VEGF,PDGF,TGF-Ƶ1,FGF,IGF-1andEGF. These growth factors have been known for their influence at different stages of the healing pro- cesses.8, 19 Basically, growth factors are low- weighted molecules produced and released by many different cell types under variable stimuli and play a determinant role in the development and maturation of different tissues in mammals. For instance, VEGF is an important regulator of angiogenic processes, increasing vessel perme- ability and contributing essentially to neoangio- genesis. Its presence in the clot of PRP can par- tially justify the positive outcomes obtained in some studies regarding the beneficial effect of PRP on capillary growth in soft-tissue wound healing.27 Severalinvitroandanimalstudieshave illustrated the modulating effect that growth factors exert on different cell types. PDGF is pri- marilyresponsiblefortissuehealingandhasbeen shown to induce proliferation of gingival fibrob- lasts and osteoblasts28 and adherence of perio- dontal ligament cells to root surfaces.29 TGF-Ƶ1 is essential for normal tissue remodeling and wound healing; it is chemotactic for human fi- broblasts,30 enhances the proliferation and dif- ferentiation ofosteoblasts,31–33 and intervenes in angiogenesis and immunomodulation.34 BFGF induces stimulation of periodontal ligament cell proliferation, osteoblastic cell proliferation and growth andfibroblasts, and plays a role in angio- genesis.35–37 IGF-1, also known as somatomedin, is a mediatorinthe activityofgrowth hormone38 and a positive regulator of cell proliferation and differentiation for most cell types.39 EGF en- hancesthe proliferation ofkeratinocytes40 and is implicated in epithelialization, wound contrac- tion and remodeling.41 Thus far, the majority of studies reporting detection of one or some of the previously men- tioned growthfactors in PRPsamples have been conducted on nonclotted samples, without any platelet activator added.3, 42–45 In our opinion, direct analysis ofthe presence of growth factors in PRP gel would provide a more accurate idea regarding which are the bioactive constituents of PRP gel. El-Sharkawy et al. performed a similar study based on a different technique, enzyme-linked immunosorbent assay (ELISA), and the same growth factor content of PRP was found.9 They quantified platelet and growth factor levels. PDGF, TGF-ʹ1, IGF-1, EGF, VEGF and bFGF were also identified in their PRP samples. They attri- buted the biological properties of these growth factors, such as proliferation of fibroblasts and periodontal ligament cells and extracellular ma- trixformation,toPRP.Luetal.alsousedthesame technique, ELISA, and they identified and quan- tifiedPRPgrowthfactorsreleased(PDGF,TGF-ʹ1 and IGF-1), obtaining similarresults, although no search for EGF, VEGF or bFGF was conducted.2 Despitethecontributionofourfindingstothe understanding of PRP biology, they also raise more questions that need to be addressed. The identification of these growth factors in PRP gel only suggests their presence in the clot, without providing evidence supporting its biologicalben- efit after its clinical usage, especiallyfor regene- rative approaches. Growth factors are proteins that, once released from the producer cell, exert a very localized action at specific ratios,46 owing to their short life span. They are labile molecules highly susceptible to denaturalization mediated by proteases present in the wound site and to phagocytosisandmightevenbecomesolubilized in the carrier.47 These undesirable events usually lead to the inactivation or annulment of the bio- logical properties of these mediators. For instance, PDGFcannot be detected in circulating blood in normal conditions, and when it is intra- venously injected, its life span is around 2min.48 This lack of long-term activity associated with the short half-life of this platelet growth factor may require repeated applications over time to maintain their therapeutic effect. Both the vehicle and concentration (dose) of biological mediators, such as platelet growth factors, may be critical factors to consider when seeking to achieve controlled modulation of cel- lular events in the desired time interval.49 How- ever, it has to be taken into consideration that there is no currently available information about the optimal dosages of PRP needed to achieve the highest effectiveness.1 It is also importantto notethatthetechnique used in this study for the detection of growth factors,Westernblotting,allowsdetectionofthe presence of a determined protein in a sample by highly specific binding of antibodies to epitopes of that polypeptide. However, it is not possible to ultimately determine whether the target pro- tein is biologically active and therefore able to exert its effect when applied to a wound. This fact, alongwiththe arguments discussed before, C o m p o s i t i o n o f P R P

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