Characterizing Spatiotemporal Population Receptive Fields in Human Visual Cortex with fMRI.

The use of fMRI and computational modeling has advanced understanding of spatial characteristics of population receptive fields (pRFs) in human visual cortex. However, we know relatively little about the spatiotemporal characteristics of pRFs because neurons' temporal properties are one to two orders of magnitude faster than fMRI BOLD responses. Here, we developed an image-computable framework to estimate spatiotemporal pRFs from fMRI data. First, we developed a simulation software that predicts fMRI responses to a time-varying visual input given a spatiotemporal pRF model and solves the model parameters. The simulator revealed that ground-truth spatiotemporal parameters can be accurately recovered at the millisecond resolution from synthesized fMRI responses. Then, using fMRI and a novel stimulus paradigm, we mapped spatiotemporal pRFs in individual voxels across human visual cortex in 10 participants (both females and males). We find that a compressive spatiotemporal (CST) pRF model better explains fMRI responses than a conventional spatial pRF model across visual areas spanning the dorsal, lateral, and ventral streams. Further, we find three organizational principles of spatiotemporal pRFs: (1) from early to later areas within a visual stream, spatial and temporal windows of pRFs progressively increase in size and show greater compressive nonlinearities, (2) later visual areas show diverging spatial and temporal windows across streams, and (3) within early visual areas (V1-V3), both spatial and temporal windows systematically increase with eccentricity. Together, this computational framework and empirical results open exciting new possibilities for modeling and measuring fine-grained spatiotemporal dynamics of neural responses using fMRI.

The interferon-regulated host factor hnRNPA0 modulates HIV-1 production by interference with LTR activity, mRNA trafficking, and programmed ribosomal frameshifting.

The interplay between host factors and viral components impacts viral replication efficiency profoundly. Members of the cellular heterogeneous nuclear ribonucleoprotein family (hnRNPs) have been extensively studied as HIV-1 host dependency factors, but whether they play a role in innate immunity is currently unknown. This study aimed to identify hnRNPA0 as a type I interferon (IFN)-repressed host factor in HIV-1-infected cells. Knockdown of hnRNPA0, a situation that mirrors conditions under IFN stimulation, increased LTR activity, export of unspliced HIV-1 mRNA, viral particle production, and thus, increased infectivity. Conversely, hnRNPA0 overexpression primarily reduced plasmid-driven and integrated HIV-1 long terminal repeat (LTR) activity, significantly decreasing total viral mRNA and protein levels. In addition, high levels of hnRNPA0 significantly reduced the HIV-1 programmed ribosomal frameshifting efficiency, resulting in a shift in the HIV-1 p55/p15 ratio. The HIV-1 alternative splice site usage remained largely unaffected by altered hnRNPA0 levels suggesting that the synergistic inhibition of the LTR activity and viral mRNA transcription, as well as impaired ribosomal frameshifting efficiency, are critical factors for efficient HIV-1 replication regulated by hnRNPA0. The pleiotropic dose-dependent effects under high or low hnRNPA0 levels were further confirmed in HIV-1-infected Jurkat cells. Finally, our study revealed that hnRNPA0 levels in PBMCs were lower in therapy-naive HIV-1-infected individuals compared to healthy controls. Our findings highlight a significant role for hnRNPA0 in HIV-1 replication and suggest that its IFN-I-regulated expression levels are critical for viral fitness allowing replication in an antiviral environment.IMPORTANCERNA-binding proteins, in particular, heterogeneous nuclear ribonucleoproteins (hnRNPs), have been extensively studied. Some act as host dependency factors for HIV-1 since they are involved in multiple cellular gene expression processes. Our study revealed hnRNPA0 as an IFN-regulated host factor, that is differently expressed after IFN-I treatment in HIV-1 target cells and lower expressed in therapy-naïve HIV-1-infected individuals. Our findings demonstrate the significant pleiotropic role of hnRNPA0 in viral replication: In high concentrations, hnRNPA0 limits viral replication by negatively regulating Tat-LTR transcription, retaining unspliced mRNA in the nucleus, and significantly impairing programmed ribosomal frameshifting. Low hnRNPA0 levels as observed in IFN-treated THP-1 cells, particularly facilitate HIV LTR activity and unspliced mRNA export, suggesting a role in innate immunity in favor of HIV replication. Understanding the mode of action between hnRNPA0 and HIV-1 gene expression might help to identify novel therapeutically strategies against HIV-1 and other viruses.

Sub-bundle based analysis reveals the role of human optic radiation in visual working memory.

White matter (WM) functional activity has been reliably detected through functional magnetic resonance imaging (fMRI). Previous studies have primarily examined WM bundles as unified entities, thereby obscuring the functional heterogeneity inherent within these bundles. Here, for the first time, we investigate the function of sub-bundles of a prototypical visual WM tract-the optic radiation (OR). We use the 7T retinotopy dataset from the Human Connectome Project (HCP) to reconstruct OR and further subdivide the OR into sub-bundles based on the fiber's termination in the primary visual cortex (V1). The population receptive field (pRF) model is then applied to evaluate the retinotopic properties of these sub-bundles, and the consistency of the pRF properties of sub-bundles with those of V1 subfields is evaluated. Furthermore, we utilize the HCP working memory dataset to evaluate the activations of the foveal and peripheral OR sub-bundles, along with LGN and V1 subfields, during 0-back and 2-back tasks. We then evaluate differences in 2bk-0bk contrast between foveal and peripheral sub-bundles (or subfields), and further examine potential relationships between 2bk-0bk contrast and 2-back task d-prime. The results show that the pRF properties of OR sub-bundles exhibit standard retinotopic properties and are typically similar to the properties of V1 subfields. Notably, activations during the 2-back task consistently surpass those under the 0-back task across foveal and peripheral OR sub-bundles, as well as LGN and V1 subfields. The foveal V1 displays significantly higher 2bk-0bk contrast than peripheral V1. The 2-back task d-prime shows strong correlations with 2bk-0bk contrast for foveal and peripheral OR fibers. These findings demonstrate that the blood oxygen level-dependent (BOLD) signals of OR sub-bundles encode high-fidelity visual information, underscoring the feasibility of assessing WM functional activity at the sub-bundle level. Additionally, the study highlights the role of OR in the top-down processes of visual working memory beyond the bottom-up processes for visual information transmission. Conclusively, this study innovatively proposes a novel paradigm for analyzing WM fiber tracts at the individual sub-bundle level and expands understanding of OR function.

Platelet-rich fibrin as an apical barrier for MTA placement in the treatment of teeth with open apices: a pilot study.

OBJECTIVE: The aim of the present pilot study was to assess the effectiveness of the platelet-rich fibrin (PRF) apical barrier for the placement of MTA for the treatment of teeth with periapical lesions and open apices. METHODS: A total of thirty teeth on twenty-eight patients with open apices and periapical periodontitis were enrolled and divided into two groups in the present pilot study. In the PRF group (fourteen teeth in thirteen patients), nonsurgical endodontic treatment was performed using PRF as an apical matrix, after which the apical plug of the MTA was created. For the non-PRF group (fourteen teeth in fourteen patients), nonsurgical endodontic therapy was performed using only the MTA for an apical plug with no further periapical intervention. Clinical findings and periapical digital radiographs were used for evaluating the healing progress after periodic follow-ups of 1, 3, 6, and 9 months. The horizontal dimension of the periapical lesion was gauged, and the changes in the dimensions were recorded each time. The Friedman test, Dunn-Bonferroni post hoc correction, and Mann-Whitney U test were used for statistical analysis, with P < 0.05 serving as the threshold for determining statistical significance. RESULTS: All patients in both groups in the present pilot study had no clinical symptoms after 1 month, with a significant reduction in the periapical lesion after periodic appointments. The lesion width of the PRF group was significantly smaller than that of the non-PRF group in the sixth and ninth month after treatment. CONCLUSIONS: PRF is a promising apical barrier matrix when combined with MTA for the treatment of teeth with open apices and periapical periodontitis. Small number of study subjects and the short time of follow-up period limit the generalizability of these results. TRIAL REGISTRATION: TCTR, TCTR20221109006. Registered 09 November 2022 - Retrospectively registered, https://www.thaiclinicaltrials.org/show/TCTR20221109006 .

Multi-omics panoramic analysis of HBV integration, transcriptional regulation, and epigenetic modifications in PLC/PRF/5 cell line.

The clearance or transcriptional silencing of integrated HBV DNA is crucial for achieving a functional cure in patients with chronic hepatitis B and reducing the risk of hepatocellular carcinoma development. The PLC/PRF/5 cell line is commonly used as an in vitro model for studying HBV integration. In this study, we employed a range of multi-omics techniques to gain a panoramic understanding of the characteristics of HBV integration in PLC/PRF/5 cells and to reveal the transcriptional regulatory mechanisms of integrated HBV DNA. Transcriptome long-read sequencing (ONT) was conducted to analyze and characterize the transcriptional activity of different HBV DNA integration sites in PLC/PRF/5 cells. Additionally, we collected data related to epigenetic regulation, including whole-genome bisulfite sequencing (WGBS), histone chromatin immunoprecipitation sequencing (ChIP-seq), and assays for transposase-accessible chromatin using sequencing (ATAC-seq), to explore the potential mechanisms involved in the transcriptional regulation of integrated HBV DNA. Long-read RNA sequencing analysis revealed significant transcriptional differences at various integration sites in the PLC/PRF/5 cell line, with higher HBV DNA transcription levels at integration sites on chr11, chr13, and the chr13/chr5 fusion chromosome t (13:5). Combining long-read DNA and RNA sequencing results, we found that transcription of integrated HBV DNA generally starts downstream of the SP1, SP2, or XP promoters. ATAC-seq data confirmed that chromatin accessibility has limited influence on the transcription of integrated HBV DNA in the PLC/PRF/5 cell line. Analysis of WGBS data showed that the methylation intensity of integrated HBV DNA was highly negatively correlated with its transcription level (r = -0.8929, p = 0.0123). After AzaD treatment, the transcription level of integrated HBV DNA significantly increased, especially for the integration chr17, which had the highest level of methylation. Through ChIP-seq data, we observed the association between histone modification of H3K4me3 and H3K9me3 with the transcription of integrated HBV DNA. Our findings suggest that the SP1, SP2 and XP in integrated HBV DNA, methylation level of surrounding host chromosome, and histone modifications affect the transcription of integrated HBV DNA in PLC/PRF/5 cells. This provides important clues for future studies on the expression and regulatory mechanisms of integrated HBV.

Impact of autologous platelet concentrates on the osseointegration of dental implants.

Osseointegration is defined as the direct deposition of bone onto biomaterial devices, most commonly composed from titanium, for the purpose of anchoring dental prostheses. The use of autologous platelet concentrates (APC) has the potential to enhance this process by modifying the interface between the host and the surface of the titanium implant. The rationale is to modify the implant surface and implant-bone interface via "biomimicry," a process whereby the deposition of the host's own proteins and extracellular matrix enhances the biocompatibility of the implant and hence accelerates the osteogenic healing process. This review of the available evidence reporting on the effect of APC on osseointegration explores in vitro laboratory studies of the interaction of APC with different implant surfaces, as well as the in vivo and clinical effects of APC on osseointegration in animal and human studies. The inherent variability associated with using autologous products, namely the unique composition of each individual's blood plasma, as well as the great variety in APC protocols, combination of biomaterials, and clinical/therapeutic application, makes it is difficult to make any firm conclusions about the in vivo and clinical effects of APC on osseointegration. The available evidence suggests that the clinical benefits of adding PRP and the liquid form of L-PRF (liquid fibrinogen) to any implant surface appear to be limited. The application of L-PRF membranes in the osteotomy site, however, may produce positive clinical effects at the early stage of healing (up to 6 weeks), by promoting early implant stability and reducing marginal bone loss, although no positive longer term effects were observed. Careful interpretation and cautious conclusions should be drawn from these findings as there were various limitations in methodology. Future studies should focus on better understanding of the influence of APCs on the biomaterial surface and designing controlled preclinical and clinical studies using standardized APC preparation and application protocols.

Periodontal regeneration using platelet-rich fibrin. Furcation defects: A systematic review with meta-analysis.

The objective of the study was to compare the treatment outcomes of periodontal furcation defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities. The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with those of other modalities for the treatment of furcation defects. Studies were classified into 11 categories in 3 different groups as follows: Group I (addition of PRF): (1) open flap debridement (OFD) alone versus OFD/PRF, (2) OFD/bone graft (OFD/BG) versus OFD/BG/PRF; Group II (comparative studies to PRF): (3) OFD/BG versus OFD/PRF, (4) OFD/collagen membrane versus OFD/PRF, (5) OFD/PRP versus OFD/PRF, (6) OFD/rhBMP2 versus OFD/PRF; and Group III (addition of biomaterial/biomolecule to PRF): OFD/PRF versus … (7) OFD/PRF/BG, (8) OFD/PRF/amniotic membrane (AM), (9) OFD/PRF/metformin, (10) OFD/PRF/bisphosphonates, (11) OFD/PRF/statins. Weighted means and forest plots were calculated for the reduction of probing pocket depth (PPD), gain of vertical and horizontal clinical attachment levels (VCAL and HCAL), gain in vertical and horizontal bone levels (VBL, HBL), and radiographic bone fill (RBF). From 45 articles identified, 21 RCTs reporting on class II furcations were included. The use of OFD/PRF and OFD/BG/PRF statistically significantly reduced PPD and improved VCAL and HCAL when compared to OFD or OFD/BG, respectively. The comparison between OFD/PRF alone versus OFD/BG, OFD/CM, OFD/PRP, or OFD/rhBMP2 led to similar outcomes for all investigated parameters, including a reduction in PPD, VCAL/HCAL gain, and RBF. The additional incorporation of a BG to OFD/PRF only mildly improved outcomes, whereas the addition of AM improved clinical outcomes. The addition of small biomolecules such as metformin, bisphosphonates, or statins all led to significant improvements in PPD, VCAL, and HCAL when compared to OFD/PRF alone. Noteworthy, a very high heterogeneity was found in the investigated studies. The use of PRF significantly improved clinical outcomes in class II furcation defects when compared to OFD alone, with similar levels being observed between OFD/PRF and/or OFD/BG, OFD/CM, OFD/PRP, or OFD/rhBMP2. Future research geared toward better understanding potential ways to enhance the regenerative properties of PRF with various small biomolecules may prove valuable for future clinical applications. Future histological research investigating PRF in human furcation defects is largely needed. The use of PRF in conjunction with OFD statistically significantly improved PPD, VCAL, and HCAL values, yielding comparable outcomes to commonly used biomaterials. The combination of PRF to bone grafts or the addition of small biomolecules may offer additional clinical benefits, thus warranting future investigation.

Essential principles for blood centrifugation.

Currently, autologous platelet concentrates (APCs) are frequently used for soft- and hard-tissue regeneration, not only within the oral cavity, but also extra-orally including chronic wounds, burns, joints, dermatological conditions, among others. The benefits of APCs are largely influenced by the treatment strategy but also their preparation. This paper therefore discusses in detail: the physical properties of blood cells, the basic principles of blood centrifugation, the impact of the centrifugation protocol (rotations/revolutions per minute, g-force, variation between centrifuges), the importance of timing during the preparation of APCs, the impact of the inner surface of the blood tubes, the use/nonuse of anticoagulants within APC tubes, the impact of the patient's hematocrit, age, and gender, as well as the important requirements for an optimal centrifugation protocol. All these variables indeed have a significant impact on the clinical outcome of APCs.

Autolougous platelet concentrates in esthetic medicine.

This narrative review summarizes current knowledge on the use of autologous platelet concentrates (APCs) in esthetic medicine, with the goal of providing clinicians with reliable information for clinical practice. APCs contain platelets that release various growth factors with potential applications in facial and dermatologic treatments. This review examines several facial esthetic applications of APCs, including acne scarring, skin rejuvenation, melasma, vitiligo, stretchmarks, peri-orbital rejuvenation, peri-oral rejuvenation, hair regeneration and the volumizing effects of APC gels. A systematic review of literature databases (PubMed/MEDLINE) was conducted up to October 2023 to identify randomized controlled trials (RCTs) in the English language on APCs for facial rejuvenation and dermatology. A total of 96 articles were selected including those on platelet rich plasma (PRP), plasma-rich in growth factors (PRGF), and platelet-rich fibrin (PRF). Clinical recommendations gained from the reviews are provided. In summary, the use of APCs in facial esthetics is a promising yet relatively recent treatment approach. Overall, the majority of studies have focused on the use of PRP with positive outcomes. Only few studies have compared PRP versus PRF with all demonstrating superior outcomes using PRF. The existing studies have limitations including small sample sizes and lack of standardized assessment criteria. Future research should utilize well-designed RCTs, incorporating appropriate controls, such as split-face comparisons, and standardized protocols for APC usage, including optimal number of sessions, interval between sessions, and objective improvement scores. Nevertheless, the most recent formulations of platelet concentrates offer clinicians an ability to improve various clinical parameters and esthetic concerns.

Differences between first- and second-generation autologous platelet concentrates.

Autologous platelet concentrates (APCs) applied alone or combined with other biomaterials are popular bioactive factors employed in regenerative medicine. The main biological rationale of using such products is to concentrate blood-derived growth factors and cells into the wound microenvironment to enhance the body's natural healing capacity. First-generation APC is represented by platelet-rich plasma (PRP). While different protocols have been documented for PRP preparation, they overall consist of two cycles of centrifugation and have important limitations related to the use of an anticoagulant first and an activator afterward, which may interfere with the natural healing process and the release of bioactive molecules. The second generation of platelet concentrates is represented by leukocyte and platelet-rich fibrin (L-PRF). L-PRF protocols involve a single centrifugation cycle and do not require the use of anticoagulants and activators, which makes the preparation more straight forward, less expensive, and eliminates potential risks associated with the use of activators. However, since no anticoagulant is employed, blood undergoes rapid clotting within the blood collection tube; hence, a timely management of L-PRF is crucial. This review provides an overview on the most documented protocols for APC preparations and critically discusses the main differences between first- and second-generation APCs in terms of cell content, protein release, and the formation of a 3D fibrin network. It appears evident that the inconsistency in reporting protocol parameters by most studies has contributed to conflicting conclusions regarding the efficacy of different APC formulations and has significantly limited the ability to interpret the results of individual clinical studies. In the future, the use of a standardized classification system, together with a detailed reporting on APC protocol parameters is warranted to make study outcomes comparable. This will also allow to clarify important aspects on the mechanism of action of APCs (like the role of leukocytes and centrifugation parameters) and to optimize the use of APCs in regenerative medicine.

How to explain the beneficial effects of platelet-rich plasma.

Platelet-rich plasma (PRP) is the platelet and leukocyte-containing plasmatic fraction of anticoagulated autologous blood. While evidence supporting the clinical use of PRP in dentistry is low, PRP is widely used in sports medicine, orthopedics, and dermatology. Its beneficial activity is commonly attributed to the growth factors released from platelets accumulating in PRP; however, evidence is indirect and not comprehensive. There is thus a demand to revisit PRP with respect to basic and translational science. This review is to (i) recapitulate protocols and tools to prepare PRP; (ii) to discuss the cellular and molecular composition of PRP with a focus on platelets, leukocytes, and the fibrin-rich extracellular matrix of coagulated plasma; and finally (iii) to discuss potential beneficial effects of PRP on a cellular and molecular level with an outlook on its current use in dentistry and other medical fields.

Dynamic changes in spatial representation within the posterior parietal cortex in response to visuomotor adaptation.

Recent studies used functional magnetic resonance imaging (fMRI) population receptive field (pRF) mapping to demonstrate that retinotopic organization extends from the primary visual cortex to ventral and dorsal visual pathways, by quantifying visual field maps, receptive field size, and laterality throughout multiple areas. Visuospatial representation in the posterior parietal cortex (PPC) is modulated by attentional deployment, raising the question of whether spatial representation in the PPC is dynamic and flexible, and whether this flexibility contributes to visuospatial learning. To answer this question, changes in spatial representation within the PPC and early visual cortex were recorded with pRF mapping before and after prism adaptation (PA)-a well-established visuomotor technique that modulates visuospatial attention according to the direction of the visual displacement. As predicted, results showed that adaptation to left-shifting prisms increases pRF size in left PPC, while leaving space representation in the early visual cortex unchanged. This is the first evidence that PA drives a dynamic reorganization of response profiles in the PPC. These findings show that spatial representations in the PPC not only reflect changes driven by attentional deployment but dynamically change in response to modulation of external factors such as manipulation of the visuospatial input during visuomotor adaptation.

Selective attention sharpens population receptive fields in human auditory cortex.

Selective attention enables the preferential processing of relevant stimulus aspects. Invasive animal studies have shown that attending a sound feature rapidly modifies neuronal tuning throughout the auditory cortex. Human neuroimaging studies have reported enhanced auditory cortical responses with selective attention. To date, it remains unclear how the results obtained with functional magnetic resonance imaging (fMRI) in humans relate to the electrophysiological findings in animal models. Here we aim to narrow the gap between animal and human research by combining a selective attention task similar in design to those used in animal electrophysiology with high spatial resolution ultra-high field fMRI at 7 Tesla. Specifically, human participants perform a detection task, whereas the probability of target occurrence varies with sound frequency. Contrary to previous fMRI studies, we show that selective attention resulted in population receptive field sharpening, and consequently reduced responses, at the attended sound frequencies. The difference between our results to those of previous fMRI studies supports the notion that the influence of selective attention on auditory cortex is diverse and may depend on context, stimulus, and task.

Development of a super-hydrophilic anaerobic tube for the optimization of platelet-rich fibrin.

Horizontal platelet-rich fibrin (H-PRF) contains a variety of bioactive growth factors and cytokines that play a key role in the process of tissue healing and regeneration. The blood collection tubes used to produce Solid-PRF (plasmatrix (PM) tubes) have previously been shown to have a great impact on the morphology, strength and composition of the final H-PRF clot. Therefore, modification to PM tubes is an important step toward the future optimization of PRF. To this end, we innovatively modified the inner wall surface of the PM tubes with plasma and adjusted the gas environment inside the PM tubes to prepare super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes). It was made anaerobic for the preparation of H-PRF with the aim of improving mechanical strength and bioactivity. The findings demonstrated that an anaerobic environment stimulated platelet activation within the PRF tubes. After compression, the prepared H-PRF membrane formed a fibrous cross-linked network with high fracture strength, ideal degradation characteristics, in addition to a significant increase in size. Thereafter, the H-PRF membranes prepared by the SHAP tubes significantly promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts while maintaining excellent biocompatibility, and advantageous antibacterial properties. In conclusion, the newly modified PRF tubes had better platelet activation properties leading to better mechanical strength, a longer degradation period, and better regenerative properties in oral cell types including gingival fibroblast and alveolar osteoblasts. It also improves the success rate of H-PRF preparation in patients with coagulation dysfunction and expands the clinical application scenario.

Why was the study done?   Direct anaerobic environment effects on fibrin formation have been insufficiently studied.The effect of hydrophilic change caused by nitrogen plasma treatment on H-PRF coagulation has not been fully studied.Optimal preparation of H-PRF in patients with poor coagulation function was needed in clinical application.What is new?  The coagulation of H-PRF correlated with the level of dissolved oxygen concentrations. Anaerobic environment significantly accelerates fibrin formation and platelet activation.Nitrogen plasma treatment can remarkably enhance the hydrophilicity of the inner surface of glass blood collecting tubes, thereby promoting the activation of platelets and the formation of fibrin network.The H-PRF prepared in the tubes with anaerobic environment and hydrophilic surface showed high fracture strength, promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts.What is the impact?  The work is aimed at developing super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes) for studying gas environment and hydrophilicity participation in fibrin formation in H-PRF preparation and investigating the influence of platelet activation in the anaerobic environment.This study provides a successful trial to convert the physiological process into biotechnological application. The SHAP tubes proposed within this article was an effective versatile H-PRF preparation device, which provided a promising alternative for tissue engineering.

Injectable platelet-rich fibrin for treatment of female pattern hair loss.

This case series evaluated use of injectable platelet rich fibrin (termed i-PRF+) for the treatment of female pattern hair loss (FPHL). Eleven individuals underwent 3-monthly intradermal injections of i-PRF+ using a mesotherapy gun. The mean number of hair follicles containing hairs per unit area improved at 3- and 6-months follow-up (p < .001), and all participants had a negative hair pull test. Hair volume and thickness, and patient-reported outcome scores also improved at follow-up (p < .001). Adverse effects were minor and self-limited. A series of three i-PRF+ injection sessions were effective for the treatment of FPHL, as shown by improved hair analysis parameters and patient self-assessment scores.

Comprehensive analysis of bone tissue in extraction sockets of third molars after leukocyte and platelet rich fibrin and photobiomodulation applications.

OBJECTIVES: The aim of this study was to compare leukocyte and platelet-rich fibrin (L-PRF) and photobiomodulation (PBM) applications, which have been repeatedly reported to be superior to control groups, in terms of pain, soft tissue and bone healing in tooth extraction sockets. MATERIALS AND METHODS: This double-blind, randomized clinical study was completed with 34 patients, who had an indication for extraction of their bilaterally impacted teeth. The right and left teeth of the patients were randomly divided into L-PRF and PBM groups. L-PRF group was treated with the blood product centrifuged for 12 min at 2700 rpm, and the PBM group was treated with a diode laser at different points for 60 s with a wavelength of 940 nm in repeated sessions. Postoperative pain was evaluated using Visual Analogue Scale (VAS), soft tissue healing with Landry Index (LI), tissue healing in the distal region of mandibular second molar by probing depth measurement, and bone healing via panoramic x-ray using the Image J program. RESULTS: No statistically significant difference was found for any variable compared between the groups. CONCLUSION: L-PRF and PBM applications provide similar support in the healing of extraction sockets. Nevertheless, the advantages and disadvantages of both methods determine their usage areas. CLINICAL RELEVANCE: While L-PRF is advantageous in the early healing of extraction sockets, PBM may be preferred in terms of bone trabeculation in the long term.

The effects of injectable platelet-rich fibrin application on wound healing following gingivectomy and gingivoplasty operations: single-blind, randomized controlled, prospective clinical study.

OBJECTIVES: The aim of this study was to evaluate the effects of wound healing using injectable platelet-rich fibrin (IPRF) after gingivectomy and gingivoplasty. MATERIALS AND METHODS: In this clinical study, 46 systemically healthy patients with chronic inflammatory gingival enlargement were randomly treated with gingivectomy-gingivoplasty + I-PRF (n=23) or gingivectomy-gingivoplasty alone (n=23). The primary outcome was to evaluate the effect of I-PRF on wound healing over a 3-week follow-up period. Samples collected from gingival crevicular fluid (GCF) were processed using enzyme-linked immunosorbent assay (ELISA) to measure VEGF and FGF-10 biomarkers. The surgical areas were stained with Mira-2 tone and evaluated in ImageJ. Wound healing was evaluated with Modified Manchester Scar (MMS) scale and Landry, Turnbull, and Howley (LTH) index. RESULTS: VEGF values of the control group at baseline, week 2, and week 3 were significantly higher than the test group. In weeks 2 and 3, FGF-10 values were found to be significantly higher in the control group than the test group. The amount of staining was found to be significantly higher in the control group than in the test group on days 3, 7, and 14. LTH values of the control group were significantly lower than the test group and MMS values were significantly higher than those of the test group. CONCLUSIONS: I-PRF applications revealed positive effects on epithelial wound healing after gingivectomy and gingivoplasty operations. CLINICAL RELEVANCE: Platelet concentrates such as I-PRF accelerate wound healing and contribute to the patient's comfort and quality of life. I-PRF application may have positive effects on wound healing after gingivectomy and gingivoplasty operations.

Antimicrobial effects of clindamycin-loaded platelet-rich fibrin (PRF).

OBJECTIVES: Recent research has demonstrated that platelet-rich fibrin (PRF) is an appropriate carrier for ampicillin/sulbactam. The aim of the study was to investigate whether PRF is also a suitable bio-carrier for clindamycin (CLI). METHODS: PRF membranes were produced from 36 patients receiving intravenous therapy with CLI (e.g. due to the diagnosis of an osteonecrosis of the jaw or infections). Concentrations of CLI in PRF membranes were measured with liquid chromatography-tandem mass spectrometry, and the antimicrobial effects were investigated in vitro in agar diffusion tests with fresh PRF and PRF stored for 24 h. Storage was performed in an incubator at 36 °C to simulate the in-vivo situation. RESULTS: The mean concentration of CLI in plasma was 1.0 ± 0.3 µg/100 mg plasma; in resulting PRF membranes 0.7 ± 0.4 µg/100 mg PRF. Agar diffusion tests were performed with Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus mitis, Porphyromonas gingivalis, and Fusobacterium nucleatum. Mean inhibition zones, in mm, for fresh PRF were 17.3, 12.2, 18.8, 17.1, 25.8 and 18.1, 12.7, 19.2, 17.3, and 26.3 for stored PRF, respectively. CONCLUSION: The results demonstrate that PRF is a suitable bio-carrier for CLI when administered systemically to patients. The concentration in PRF generated from patients after infusion of 600 mg CLI dose suffices to target clinically relevant bacteria. CLINICAL RELEVANCE: Using PRF as a carrier for local antibiotic application can prevent infections in oral and maxillofacial surgery. Within the study limitations, the findings could expand the scope of PRF application by adding CLI as a new antibiotic to the spectrum of PRF therapy.

Comprehensive analysis of L-PRF exudate components and their impact on whole blood platelets.

OBJECTIVE: This study assessed the cellular composition and effects of leukocyte-platelet-rich fibrin (L-PRF) exudate on whole blood platelets from healthy volunteers. Key objectives included evaluating leukocyte subpopulations, platelet activation markers, platelet-leukocyte interactions and quantifying inflammatory cytokines within the L-PRF exudate. MATERIALS AND METHODS: L-PRF was obtained from 20 healthy donors. Flow cytometry methodologies were used to assess intracellular calcium kinetics and activated GPIIbIIIa, and P-selectin expression. Leukocyte subpopulations and platelet-leukocyte interactions were characterized using monoclonal antibodies. Inflammatory cytokines (IL-8, IL-1ß, IL-6, IL-10, TNF, IL-12p70) within L-PRF exudate were quantified using a cytometric bead array. RESULTS: The expression of activated GPIIbIIIa, and P-selectin exhibited a significant increase (p < 0.001) when L-PRF exudate was added to platelets of whole blood. Regarding intracellular Ca2+ mobilization, the L-PRF exudate elicited significant responses (p < 0.001). L-PRF exudate contained different leukocytes populations, being TCD4 + the most representative of T cells. It was possible to stablish a profile of cytokines produced by the L-PRF exudate, with human IL-8 cytokine exhibiting the highest average (16.90 pg/mL). CONCLUSIONS: Despite the study limitations, the research yielded important insights: 1- L-PRF exudate can stimulate platelet activation, essential in healing, tissue inflammation and remodeling. 2-The presence of leukocyte subpopulations within L-PRF exudate reflexes its complexity and potential to enhance immune responses. 3-The analysis of inflammatory cytokines within L-PRF exudate revealed its immunomodulatory potential. These findings are valuable evidences for understanding the potential role of L-PRF exudate in regenerative dentistry and medicine, offering innovative therapeutic strategies. CLINICAL RELEVANCE: This research highlights crucial aspects that could significantly influence the clinical use of L-PRF exudate in the oral cavity. The findings support the application of L-PRF exudate in both surgical and regenerative dentistry, facilitating the development of innovative therapeutic strategies to enhance patient outcomes.

Evaluation of advanced platelet-rich fibrin compared to subepithelial connective tissue graft in the surgical management of interdental papilla recession: a randomized controlled trial.

OBJECTIVES: The current study aims to compare advanced-platelet-rich fibrin membrane (A-PRF) to connective tissue graft (CTG) using Han and Takei's approach. MATERIALS AND METHODS: The defective papilla was randomly allocated to either the control group (CTG) or to the experimental group (A-PRF). Papilla height (PH) and percent change in the gingival black triangle (GBT) area were recorded at 1, 3, 6, 9, and 12 months. RESULTS: Thirty-two deficient IDPs with an initial papilla presence index (PPI) of 2 or 3 were included. At 12 months, the papilla-fill significantly increased in both groups (p < 0.001) without a significant difference between the study groups (p = 0.637). A mean gain in IDP height of 2.25 mm (± 0.97) in the CTG group and 1.86 mm (± 0.7) in the A-PRF group were recorded with a nonsignificant difference. Gingival black triangle fill showed a 57.98% fill in the CTG and 54.65% fill in the A-PRF group, with no statistically significant difference between the groups (0.956). Regarding postoperative pain patients, the CTG group consumed significantly more analgesics than the A-PRF group (11.75 ± 3.51 and 8 ± 3.08, respectively, with p = 0.003). CONCLUSION: Both CTG and A-PRF were found to be equally effective in increasing deficient IDP height with Han and Takei's surgical technique, with no significant difference. Within the current study's limitations, A-PRF seems to be a viable alternative to CTG in the treatment of GBTs. CLINICAL RELEVANCE: Multilayered A-PRF membrane can be used as a choice in the augmentation of receded papillae, using Han and Takei's technique.