Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution.

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates geared to simplified preparation without biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibrin adhesives, concentrated platelet-rich plasma (cPRP) and PRF. Indeed, the 3-dimensional fibrin architecture is deeply dependent on artificial clinical polymerization processes, such as massive bovine thrombin addition. Currently, the slow polymerization during PRF preparation seems to generate a fibrin network very similar to the natural one. Such a network leads to a more efficient cell migration and proliferation and thus cicatrization.     

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part IV: clinical effects on tissue healing.

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this fourth article, investigation is made into the previously evaluated biology of PRF with the first established clinical results, to determine the potential fields of application for this biomaterial. The reasoning is structured around 4 fundamental events of cicatrization, namely, angiogenesis, immune control, circulating stem cells trapping, and wound-covering epithelialization. All of the known clinical applications of PRF highlight an accelerated tissue cicatrization due to the development of effective neovascularization, accelerated wound closing with fast cicatricial tissue remodelling, and nearly total absence of infectious events. This initial research therefore makes it possible to plan several future PRF applications, including plastic and bone surgery, provided that the real effects are evaluated both impartially and rigorously.     

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates?

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this third article, we investigate the immune features of this biomaterial. During PRF processing, leucocytes could also secrete cytokines in reaction to the hemostatic and inflammatory phenomena artificially induced in the centrifuged tube. We therefore undertook to quantify 5 significant cell mediators within platelet poor plasma supernatant and PRF clot exudate serum: 3 proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), an antiinflammatory cytokine (IL-4), and a key growth promoter of angiogenesis (VEGF). Our data are correlated with that obtained in plasma (nonactivated blood) and in sera (activated blood). These initial analyses revealed that PRF could be an immune regulation node with inflammation retrocontrol abilities. This concept could explain the reduction of postoperative infections when PRF is used as surgical additive.     

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part V: histologic evaluations of PRF effects on bone allograft maturation in sinus lift.

OBJECTIVE: Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. The use of platelet gel to improve bone regeneration is a recent technique in implantology. However, the biologic properties and real effects of such products remain controversial. In this article, we therefore attempt to evaluate the potential of PRF in combination with freeze-dried bone allograft (FDBA) (Phoenix; TBF, France) to enhance bone regeneration in sinus floor elevation. STUDY DESIGN: Nine sinus floor augmentations were performed. In 6 sites, PRF was added to FDBA particles (test group), and in 3 sites FDBA without PRF was used (control group). Four months later for the test group and 8 months later for the control group, bone specimens were harvested from the augmented region during the implant insertion procedure. These specimens were treated for histologic analysis. RESULTS: Histologic evaluations reveal the presence of residual bone surrounded by newly formed bone and connective tissue. After 4 months of healing time, histologic maturation of the test group appears to be identical to that of the control group after a period of 8 months. Moreover, the quantities of newly formed bone were equivalent between the 2 protocols. CONCLUSIONS: Sinus floor augmentation with FDBA and PRF leads to a reduction of healing time prior to implant placement. From a histologic point of view, this healing time could be reduced to 4 months, but large-scale studies are still necessary to validate these first results.     

Platelet-rich fibrin (PRF) in implant dentistry in combination with new bone regenerative technique in elderly patients

IntroductionSome studies have demonstrated that platelet rich fibrin (PRF) is a healing biomaterial with a great potential for bone and soft tissue regeneration, without any inflammatory reactions and may be used alone or in combination with bone grafts, promoting hemostasis, bone growth, and maturation. PRF appears as a natural and satisfactory aid in bone regenerative surgery in elderly patients with favorable results and low risks.AimThis study wants to demonstrate how PRF in association with a new split crest augmentation technique can be a great aid in implant rehabilitation, especially in the elderly patients, when bone regeneration is required.Materials and methodsTen patients were treated in this study, five following the flapless split crest new procedure and other five patients following traditional procedure without split crest as control. Five patients with an average age between 50 and 60 years were selected to be operated with a split crest flapless modified technique in order to optimize the regenerative conditions with a bone augmentation and implant insertion in one single stage procedure. For all the patients autologous PRF has been used to fill the split crest gap or simply as regenerative material. Orthopantomography, intraoral radiography and CT DentaScan/CT Cone beam were performed for every patient before the treatment and at follow-up time exeption made for CT.ResultsAll cases were successful, there were no problems at surgery time, at post-operative and at osteointegration periods. All implants achieved osteointegration. These results were obtained by accurately managing immediate and late post operative period in all of the operated cases. Mean difference for height bone loss between the two groups of patients was 2.4 mm at T1 and 2.2 mm at T3.DiscussionThe rationale of this split crest flapless modified technique is to obtain a proper buccal cortex expansion preserving its vascular supply avoiding periosteal elevation for better cortical bone nourishing. Moreover, advantages are reported related to the use of PRF. The effectiveness of PRF is shown in promoting the healing of surgical wounds, it has, in fact, platelet growth factors that can improve the vascularisation of the surgical site, promoting neoangiogenesis. Furthermore, by simply changing the settings of the centrifuge, it is possible to obtain a normal gelling if it has to be used as regenerative and stimulating material, or more consistent substance to be used as a filler in the split crest gap.ConclusionsThe main advantages in using the platelet-rich fibrin are healing and bone regenerative properties in combination with its complete resorption after surgery, thus avoiding a second surgery time, important factor in the elderly patients. Currently, it is a minimally invasive technique with low risks and satisfactory clinical results such preventing complications or implant failure particularly in elderly patients for age related conditions.     

Platelet-rich plasma and platelet gel: a review

Strategies to reduce blood loss and transfusion of allogeneic blood products during surgical procedures are important in modern times. The most important and well-known autologous techniques are preoperative autologous predonation, hemodilution, perioperative red cell salvage, postoperative wound blood autotransfusion, and pharmacologic modulation of the hemostatic process. At present, new developments in the preparation of preoperative autologous blood component therapy by whole blood platelet-rich plasma (PRP) and platelet-poor plasma (PPP) sequestration have evolved. This technique has been proven to reduce the number of allogeneic blood transfusions during open heart surgery and orthopedic operations. Moreover, platelet gel and fibrin sealant derived from PRP and PPP mixed with thrombin, respectively, can be exogenously applied to tissues to promote wound healing, bone growth, and tissue sealing. However, to our disappointment, not many well-designed scientific studies are available, and many anecdotic stories exist, whereas questions remain to be answered. We therefore decided to study perioperative blood management in more detail with emphasis on the application and production of autologous platelet gel and the use of fibrin sealant. This review addresses a large variety of aspects relevant to platelets, platelet-rich plasma, and the application of platelet gel. In addition, an overview of recent animal and human studies is presented.     

Comparison of a plasma-based composite biologic sealant with fibrin glue (Tisseel) for vascular anastomoses

Biologic sealants are needed in numerous, more and more demanding, procedures--especially with developments occurring in endovascular and laparoscopic vascular techniques. An initial pilot study in dogs showed that a 4-cm aortotomy closed with a polyester patch sutured in place by a 4-mm-spaced running suture consistently led to massive hemorrhage. We then designed a study using five dogs where two aortotomies were done to compare the effect of Tisseel to that of an autologous sealant prepared in our laboratory. Arterial pressures and heparinization were maintained throughout the surgical procedure. Both biologic sealants prevented hemorrhage from the arteriotomy at unclamping. Macroscopic and histologic assessments were performed. At killing, one week later, the autologous sealant exhibited less blood saturation of the collagen sponge compared with Tisseel. The use of autologous plasma combined with other adhesive components could be an efficient alternative to allogenic fibrin glue. Further studies are needed to confirm these observations.     

Structural features of angiotensin II which are important for biologic activity.

In summary, the aromatic ring of phenylalanine (COOH-terminus) is the key to the intrinsic activity with Tyr4, also involved in activation of a response. The NH2-terminal residue is a determinant of duration of action. The side chains of Tyr4 and His6 are key determinants for affinity, and the amino acids in the No. 1 and No. 2 position also contribute to receptor binding. Val3, Ile5, and Pro7 contain neutral side chains which probably establish and/or help maintain the appropriate distances among the key sidechains of Tyr4, His6, and Phe8. In other words, Val3, Ile5 (or Val), and Pro7 are key determinants of structural conformation.     

Biomarkers of pituitary neoplasms: a review (Part II)

Several new markers have shown a capacity to predict the clinicopathological behavior of pituitary neoplasms; these markers have shown potential to correlate with tumor subtype and size and patient age and sex. These various markers are involved in a host of cellular functions, including cell-cycle progression, cell proliferation, apoptosis, cell adhesion, and tumor vascularity. In this companion article to our first review of Ki-67 as a marker of pituitary adenomas, we present and analyze the literature regarding matrix metalloproteinases and their inhibitors (tissue inhibitor metalloproteinases), vascular endothelial growth factor, fibroblast growth factor and its receptor, apoptotic markers and p53, as well as cyclooxygenase-2, galectin-3, and pituitary tumor transforming gene. Some of these markers, such as fibroblast growth factor and fibroblast growth factor receptor and matrix metalloproteinases, show particular promise in their ability to identify pituitary tumors that behave in an aggressive manner. We suggest the need for uniform design and application of methods and standardized criteria for the interpretation of results. A uniform approach will establish clinicopathological utility of emerging markers.     

Renal amyloidosis (Part II)

As reported in the previous chapter (Part I) the term amyloidosis refers to the deposition of an amorphous substance defined by the presence of fibrillary structure by electron microscopy and a characteristic betapleated sheet structure by X-ray diffraction. Renal biopsy is fundamental in diagnostic terms because morphological demonstration is necessary and the tissue most frequently involved by amyloidosis is the kidney. In the previous chapter we presented the different histochemical and immunohistochemical techniques that are necessary to differentiate the two main types of amyloidosis defined as AL and AA. Here we show the variability of deposition of amyloid in glomerular, vascular and interstitial compartments.     

Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features.

Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive Epstein-Barr virus-associated B-cell lymphoproliferative disorder (EBV-BLPD), varying widely from an indolent process to an aggressive large cell lymphoma. The skin is the extrapulmonary organ most commonly involved in LYG. We studied 32 skin lesions from 20 patients with known pulmonary LYG, using immunohistochemistry, in situ hybridization for EBV, and polymerase chain reaction for the presence of antigen receptor gene rearrangements (IgH and TCR) to better define both the clinicopathologic spectrum and pathogenesis of the cutaneous lesions. We describe two distinct patterns of cutaneous involvement. Multiple erythematous dermal papules and/or subcutaneous nodules, with or without ulceration, were present in 17 patients (85%). These lesions demonstrate a marked angiocentric lymphohistiocytic infiltrate, composed predominantly of CD4-positive T-cells, with a high propensity for involving the subcutaneous tissues, and exhibiting angiodestruction, necrosis, and cytologic atypia. EBV-positive B-cells were detected in the nodules from five patients; clonal immunoglobulin heavy chain gene (IgH) rearrangements were detected by polymerase chain reaction in two patients. Multiple indurated, erythematous to white plaques were present in three patients (15%). The plaque lesions were negative for EBV and clonal IgH gene rearrangements in all cases studied. The clinical course of overall disease was variable, ranging from spontaneous regression without treatment (1 of 13; 7%), resolution with chemo/immunomodulatory therapy (8 of 13; 62%), and progression (4 of 13; 31%). The clinical and histopathologic features of cutaneous LYG are extremely diverse. However, the majority (85%) of the cutaneous lesions mirrors to some extent LYG in the lung, although EBV+ cells are less frequently identified. This subset of cases shows the histopathologic triad of angiodestruction with associated necrosis, panniculitis, and in some cases atypical lymphoid cells. The commonality of the histologic features in this group suggests a common pathophysiologic basis, possibly mediated by cytokines and chemokines induced by EBV. A small percentage of the lesions (15%) presented as indurated and atrophic plaques, and EBV was not identified in the small number of cases studied. The relationship of the plaque-like lesions to LYG remains uncertain. Whereas some cases of LYG regress spontaneously, most require therapy.     

Microvascular anastomosis with a low-output carbon dioxide (CO2) laser. II. Histopathological features

A low-output CO2 laser was applied for microvascular anastomosis. The healing process of the vessel wall was examined histopathologically using light and scanning electron microscopes, and compared with that following conventional suture anastomosis. A power level of 21-40 mW and an exposure time of 5-15 sec were used. Under these conditions the laser beam reached the adventitia and media but not the intima. This made it possible to perform microvascular anastomosis without causing damage to the intima. Inflammatory reactions in the vessel wall were milder and endothelialization of the lumen surface occurred somewhat earlier with the laser technique than with the conventional technique of manual suture anastomosis.     

Hypothalamo-pituitary-adrenal function in pituitary adenoma and craniopharyngioma. Part II: insulin test and clinical features.

For the assessment of hypothalamic corticotropin releasing hormone (CRH) secretory function, insulin test, lysinevasopressin test, and rapid ACTH test were performed and plasma crotisol was assayed. Disturbances of CRH secretory activities were found not to be related with the degree of suprasellar extension of tumors, contents of tumors, the degree of visual disturbances, or the duration of symptoms, and it was supposed that more complex mechanisms were responsible for CRH secretory abnormalities.