Leukocyte and platelet-rich fibrin (PRF), a second-generation platelet concentrate has been the focus of intensive research endeavors over the last 2 decades. Over the years, numerous reports have however failed to accurately report g-force values which have caused considerable confusion in the field. These values have since been re-transcribed incorrectly in many studies moving forward, and this article aims to address this topic to avoid further confusion in the field. We address several reports in which PRF centrifugal g-forces have been calculated at the PRF clot (referred to as relative centrifugal force [RCF]-clot) as opposed to the international standard method described at the bottom of centrifugation tubes (RCF-max). We further highlight how RCF-clot is not only a deviation from the standard international method used to report g-force values, but one subject to significant error owing to centrifugation time, patient hematocrit levels, initial volume of blood collected, and other factors. For these reasons and those further reported throughout this article, we address this controversy in detail to avoid further confusion regarding the report of g-force values in future studies. Furthermore, we propose a standardization regarding the accurate report of g-force values in future studies investigating PRF at the RCF-max.

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Background: One of the main issues pertaining to the use of fibrin membranes today, is their clinical efficacy for guided bone regeneration. This requires the need for membrane stability and a controlled resorption that enables the barrier to remain functionally during a relevant clinical time span. Human serum albumin is known to have an impact in the formation and stability of the fibrin networks density and permeability. Therefore, its interaction with fibrin aggregates may provide interesting features to autologous blood-derived biomaterials. Aim: In this context, the present study sought to characterize membranes produced through a modified protocol for concentrated growth factors (CGF) associated with activated plasma albumin gel (APAG). Method: Mixing denaturized albumin with CGF from the same blood samples into glass containers resulted in solid malleable membranes, with a modified denser ultrastructure as revealed by scanning electron microscopy (SEM). Results: The membranes presented a high density of nucleated cells, uniformly distributed along its length, and were able to release growth factors such as PDGF, VEGF, and FGF2 for 7 days. Conclusion: This preliminary study indicates that the protocol may provide autologous moldable and stable biomaterials for use as a soft tissue barrier, offering the basis for further research on its effectiveness for guided tissue regeneration.

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Investigations of endogenous blood-derived growth factors have increased in the past two decades. The initial protocols for blood concentrates, such as platelet-rich-plasma, utilized anticoagulants followed by bovine thrombin to catalyze fibrin polymerization. Subsequently, platelet-rich-fibrin (PRF) protocol was developed to eliminate anticoagulants and thrombin. The PRF production was described in a vertical rotor centrifuge with an angle of ~33°. Many commercial enterprises have attempted to replicate this protocol with a multitude of different centrifuges. These attempts have utilized revolutions per minute (RPM) to develop their protocol to generate PRF. However, RPM is a variable parameter, as it depends on the design and radius of the centrifuge. The separation of blood components is highly dependent on the relative centrifugal force (RCF) generated, which is based on the applied centrifugal force, expressed as multiples of earth's gravitation (g) field. RCF is a function of the acceleration due to the gravity of the earth, g = 9.81 m/s² RCF, not RPM, is the key factor for the sedimentation of the cells and proteins within blood concentrates. RCF is determined using the maximum centrifuge radius for calculation. The initial PRF was generated by applying an RCF of 700 ×g. Accordingly, so far, a large number of studies existing about PRF are not comparable, as they were technically prepared with different RCFs. In addition, due to the nonstandardized measurement methods, in some published studies, incorrect RCF values are published as the authors did not know how to calculate the RCF correctly. This is the case for a widespread blood concentrate called leukocyte-PRF, which is commercially available. Recently, we introduced the low-speed centrifugation concept (LSCC) for the production for solid and liquid PRF matrices. This concept is based on the above-mentioned initial PRF protocols, which represents a relatively high RCF. It shows that a systematic reduction of 700 ×g to 44 ×g can significantly increase the cells and growth factors within the same blood concentrates. The LSCC concept was established initially for a fixed rotor centrifuge with a radius of ~110 mm. The present narrative review highlights the necessity of standardization in the generation of blood concentrates, which utilizes RCF, rather than commercial protocols.

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The advance of surgical techniques and modifications with respect to the surface and macrogeometry of dental implants, such as immediate and early loading, can help reduce the time of rehabilitation for the patient when excellent primary stability is the primary prerequisite. Starting from this principle, studies using a novel technique to replace bone-subtractive drilling have been developed to optimize the implant site. This new technique, called osseodensification, was developed by Dr. Salah Huwais and patented in 2012. The name of the procedure suggests the induction of a compression wave at the tip of specially designed drills at the point of contact. This case report suggests that the clinical and radiographic results obtained could support the hypothesis that a true gain in primary stability as well as a compaction grafting can be achieved by the use of this technique.

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Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) regenerative therapy lacks evidence to make clinical decisions. This weakness cannot be addressed only by standardization of preparation protocols and devices. In this article, we have emphasized on the necessity for quality testing to obtain strong evidence supporting PRP/PRF therapy.

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Aim: The aim of this pilot study was to assess the performance of autologous tooth matrix, used as a graft material for maxillary sinus augmentation, after at least 1-year of follow-up. Settings and Design: The patients included in this prospective case series study were treated in four clinical centers using standardized clinical procedures. Materials and Methods: Patients with atrophic posterior maxilla in need of sinus augmentation before rehabilitation with implant-supported prostheses, and with compromised teeth to be extracted, were included. The extracted tooth was cleaned and processed by a recently introduced automated device, which allows fragmentation and partial demineralization of the tooth matrix, and used as a graft material for sinus augmentation. A covering membrane was used to protect the graft. Implants were placed after 6 months of healing. Five bone biopsies of the grafted sites were taken at the time of implant surgery, for histological analysis. Implants were followed for at least 1 year after placement. Cone-beam computed tomography and/or standardized periapical radiographs were used to assess the ridge height before and after grafting, up to 1-year postimplantation. Statistical Analysis: Descriptive statistics were used to synthesize the results, using mean values and standard deviations. Results: Twenty-three patients (9 males, mean age at surgery 57.1 ± 9.4 years) were treated and 40 implants were placed in grafted sites. Residual ridge height was 5.22 ± 2.04 mm and increased to 14.72 ± 2.83 mm after grafting. One implant failed during healing phase. Cumulative implant survival rate was 97.5% after 19.1 ± 8.0 months of follow-up (range 12.3–44.1 months). After 6 months of healing, the graft height appeared stable. No signs of sinus infection were present. The histologic analysis revealed neither inflammatory nor infective reaction against tooth graft. Granules appeared surrounded by newly formed bone and partially resorbed, indicating ongoing remodeling. Conclusion: Autologous human tooth matrix can be successfully used as graft material in sinus augmentation procedure.

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Platelet-rich fibrin (PRF) is a blood concentrate system derived from the peripheral blood by means of centrifugation. In esthetic medicine, hyaluronic acid (HA) is safe and most frequently used for esthetic treatment and skin augmentation. However, some complications such as inflammation were reported in the literature after the injection of HA as a xenogeneic material. The present case report presents a case of the treatment of complication after HA injection. The subject received the injection of HA in combination with filler material and developed a purulent and granulomatous dermal and subdermal skin infection that was eliminated by incision. To prevent scar formation, the subject was treated with dermal and subdermal liquid PRF injections for 1 year, and the case was documented for 2 years. The PRF injections promoted wound healing and minimized the scar formation. After two sessions, the patient swelling and redness were significantly decreased compared to baseline. After 4 sessions, complete wound healing was achieved without obvious scar formation. This case report shows that the use of liquid PRF as a bioactive system promotes wound healing and skin regeneration as well as minimizes scar formation. However, controlled clinical studies are needed to further elucidate the benefit of PRF as an autologous and bioactive material for esthetic skin treatment.

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In the last decade, an increasing awareness was directed to the role of Vitamin D in nonskeletal and preventive roles for chronic diseases in different fields. Vitamin D deficiency was reported in many countries worldwide and is considered as a pandemic. However, no consensus exists about whether and how supplementation of Vitamin D may be beneficial as a preventive or adjuvant therapy. Thereby, this review aimed to deliver an overview about the administrated doses of Vitamin D in randomized controlled clinical studies, in order to evaluate the currently available clinical evidence. In addition, focus was placed on the recent advances on Vitamin D nonskeletal actions. The results sometimes showed a great discrepancy between the recommended Vitamin D dose by different guideline authorities, which are from 400 to 4000 IU/day, and the used doses in recent randomized controlled clinical studies, which were up to 100,000 IU/day. Different studies showed the positive effect of Vitamin D in supporting the immune system and preventing different chronic and infectious diseases. These findings reflect the need to rethink existing reference ranges and intake recommendations. Based on the analyzed range of clinically applied doses, we recommend a Vitamin D supplementation based on three different ranges, which include <40 ng/ml, >40 <80 ng/ml, and >80 ng/ml with oral Vitamin D intake of 10,000 IU/day, 5000 IU/day, and 1000 IU/day, respectively. A 25-hydroxyvitamin D blood serum monitoring is furthermore recommenced every 3 months to re-adjust the Vitamin D dose based on the above-mentioned concept. Ongoing clinical studies will have to further prove this concept for different patient groups.

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Medication-related osteonecrosis of the jaw (MRONJ) is a drug-related adverse event consisting of progressive bone destruction in the maxillofacial region of patients under current or previous treatment with antiresorptive or antiangiogenic medications. Autologous platelet concentrates (APC) demonstrated to enhance bone and soft-tissue healing in many oral surgery procedures. This systematic review aimed to evaluate APC effect for treatment and prevention of MRONJ in patients under antiresorptive therapy. An electronic search was performed on MEDLINE, Scopus, Web of Science, and Cochrane databases using specific search terms, combined with AND, OR. Both prospective and retrospective studies with at least three patients and 3 months' follow-up were included, and they underwent data extraction and risk of bias assessment. When possible, a meta-analysis was undertaken. Eighteen studies reporting on 946 patients were included in this study. Postsurgery follow-up ranged from 3 to 94 months. The adjunct of APC in MRONJ treatment significantly reduced osteonecrosis recurrence with respect to control (P = 0.001). APC was also beneficial for MRONJ prevention, being associated with a lower MRONJ incidence after tooth extraction (P = 0.03). Heterogeneity was found regarding medication type, clinical indication, triggering factors, study design, follow-up duration, type of APC, and outcomes adopted to evaluate treatment success. Although the results of this review must be cautiously interpreted, due to the low-evidence level and limited sample size of the studies included, they are suggestive for possible benefits of APC when associated with surgical procedures for treatment of MRONJ. To confirm such indication, further prospective comparative studies with large sample size are urgently needed.

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The aim of this case report was to describe an alternative treatment for the healing and maintenance of peri-implant mucosa in esthetical region. Managing the peri-implant soft tissue is one of the most challenging tasks in anterior implant esthetics, especially when replacing a failing tooth. However, not all patients underwent extraction, and immediate implant placement can receive loading, conducting to uncertain predictability. This is a case report that describes an alternative treatment for the healing and maintenance of the peri-implant mucosa in an esthetically significant region, through the use of a customized abutment to obtain an emergency profile when there is insufficient torque for immediate implant loading. The present technique was able to ensure not only healthy peri-implant soft and hard tissues, but also esthetic maintenance of the anterior region for immediate implant placement. This clinical case demonstrates a different manipulation technique from the peri-implant soft tissues in immediate implants of the esthetic region favoring the peri-implant health and clinical results, promoting treatment success, and patient satisfaction.

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Purpose: The aim of the study is to histologically evaluate new bone formation in extraction sockets augmented with autologous demineralized dentin bone (ADDB). Materials and Methods: Teeth were extracted from 19 patients and prepared as ADDB and then grafted in 27 extraction socket sites. The graft was covered with membrane made of concentrated growth factors (membrane) and the wounds were closed without periosteal releasing incision (open-membrane technique). Bone biopsy was performed at each implant site after 4 months of healing. Results: Wound healing was uneventful. Histologically, bone reformation was observed in all the augmented sockets, and ADDB showed favorable integration with newly formed bone. Conclusion: Immediate graft after extraction using ADDB is recommended for socket preservation.

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Naturally derived bone substitute materials have to undergo controlled purification processes to be suitable for clinical application. The aim of the present article is to analyze the structure and composition of a new commercially available bovine-derived bone substitute material, SmartBone^®, for the presence and localization of organic and inorganic constituents. Standardized conventional methods were performed for the histological analysis using hematoxylin and eosin, Azan, Masson-Goldner trichrome, as well as specific tartrate-resistant acid phosphatase staining, and were evaluated by light microscopy. The results showed a calcified trabecular structure with preserved lamellar substructure. In addition, organic structures were found within the osteocyte lacunae, the haversian canals, and the inter-trabecular region. The presence of organic remnants within the bone block raises the question on what extent including organic material could affect the regeneration process and application safety in clinical settings and whether including specific organic material such as collagen could be beneficial for bone regeneration. Thereby, further preclinical and clinical studies are necessary to evaluate the bone block examined here and to determine whether a clinician should accept the organic remnants within bone blocks.

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Background: The use of Vitamin D₃, as an alternative drug, combined with common therapeutic strategies to treat nonmelanoma skin cancers, has recently attracted attention. However, in vitro data on Vitamin D₃action on different tumor cell lines compared to healthy cells are lacking. Aims and Objectives: In this context, the present study aimed to investigate the potential role of Vitamin D₃'s ability as an antitumor treatment. Materials and Methods: Cell growth, cell viability, and apoptosis as well as cell cycle distribution were comparatively assessed in a squamous cell carcinoma (SCC) cell line, a basal cell carcinoma (BCC) cell line, and healthy primary normal human epidermal keratinocytes (NHEK) in response to various Vitamin D₃concentrations. Results: Tumor and healthy cells clearly responded differently to Vitamin D₃application with regard to metabolic activity and apoptosis. The application of Vitamin D₃reduced the metabolic activity of the BCC and SCC cancer cell lines (and not NHEK) and induced cell cycle arrest. Furthermore, Vitamin D₃-mediated increased apoptosis was observed in tumor cells but not in healthy primary keratinocytes. Conclusions: Our findings indicate an antiproliferative and proapoptotic Vitamin D₃-dependent effect on skin cancer cells in vitro, highlighting Vitamin D₃as a potential and beneficial alternative drug for further studies with respect to possible clinical strategies to treat nonmelanoma skin cancers.

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The use of platelet-rich fibrin has gained importance as an autologous scaffold for tissue regeneration. One of its features is, when placing implants in fresh extraction sockets, to function as a selective scaffold and also as a barrier in order to correct marginal bone defects and/or to avoid collapse of surrounding soft tissue. However, its handling and placement require specific manipulation skills, to avoid unintentional slipping and dislodging during the suture procedure. In order to avoid these problems and to allow easier and faster use of the PRF matrix, a simple device for providing a self-stabilized fibrin plug has been developed. This plug surrounds, as an elastic ring, the transmucosal extension of the prosthetic components for conical internal connection implants, thus enhancing the effectiveness of the fibrin matrix expected performance.

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