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Background and Objective: Macrophages’ cytokine expression and polarization play a substantial role in the host's “destructive” inflammatory response to periodontal and peri‐implant pathogens. This study aimed to evaluate cell viability, anti‐inflammatory activity, and macrophage polarization properties of different cranberry concentrates.
Methods: THP‐1 cells (monocytic line) were treated with phorbol myristic acid to induce macrophage differentiation. Human gingival fibroblasts (HFIB‐G cell line), osteosarcoma‐derived osteoblasts (SAOS‐2 cell line), and induced macrophages were treated with cranberry concentrates at 25, 50, and 100 µg/mL for 120 seconds, 1 hour and 24 hours. Untreated cells at the same time points served as controls. For anti‐inflammatory analysis, induced macrophages exposed to cranberry concentrates (A‐type PACs) were stimulated with lipopolysaccharides (LPS) derived from E coli for 24 hours. Cell viability, interleukin (IL)‐8, IL‐1 ß, IL‐6, and IL‐10 expression of LPS‐stimulated macrophages, and macrophage polarization markers were evaluated through determination of live‐cell protease activity, enzyme‐linked immunosorbent assay, and immunofluorescence staining semi‐quantification.
Results: Cranberry concentrates (A‐type PACs) did not reduce HGF, SAOS‐2, and macrophage viability after 24 hours of exposure. Pro‐inflammatory cytokine expression (ie IL‐8 and IL‐6) was downregulated in LPS‐stimulated macrophages by cranberry concentrates at 50 and 100 µg/mL. Anti‐inflammatory IL‐10 expression was significantly upregulated in LPS‐stimulated macrophages by cranberry concentrates at 100 µg/mL after 24 hours of exposure. M1 polarization significantly decreased when LPS‐stimulated macrophages were exposed to cranberry concentrates. High levels of positive M1 macrophages were present in all untreated control groups. M2 polarization significantly increased at all LPS‐stimulated macrophages exposed to cranberry concentrates for 1 and 24 hours.
Conclusion: Cranberry‐derived proanthocyanidins may have the potential to act as an anti‐inflammatory component in the therapy of periodontal and peri‐implant diseases.
Background: Deep surgical site infections (dSSIs) after instrumented spinal surgery pose major therapeutic challenges. Standard treatment involves surgical debridement, wound drainage, and long-term antibiotic administration. Autologous platelet-rich fibrin (PRF) constitutes a biomaterial obtained from patients’ own blood that contains leukocytes, chemokines and growth factors boosting cicatrization. Due to favorable results reported from other surgical disciplines such as dentistry, orthopedics, maxillofacial and plastic surgery using PRF, the authors hypothesized that PRF augmentation will promote wound healing in dSSIs. Objective: To report our preliminary results on the safety and efficacy of autologous-PRF as an add-on therapy on a pilot case series of persistent dSSI after instrumented spinal surgery. Methods: Among the 293 patients who underwent dorsal decompression and stabilization of the cervical, thoracic, and lumbar spine due to degenerative diseases in our department, 12 patients (4%) presented persisting dSSI after standard wound debridement and antibiotic treatment. PRF augmentation was used during a second surgical revision as an add-on therapy to standard debridement. In all cases, the wound was primarily closed without drains. Results: Wound healing was completed between 14 and 21 days after the second surgical revision in all patients. At a median follow-up of 8 months (range: 6 to 18 months), no recurrence of dSSI nor complications were encountered in any case. Conclusions: Our preliminary results suggest that PRF augmentation in persistent dSSI after instrumented spinal surgery appears to be a safe and effective strategy to promote wound healing. Prospective controlled studies are required to define the efficiency of PRF more clearly in both treating and preventing dSSI.
Various strategies have been employed to speed tissue regeneration using bioactive molecules. Interestingly, platelet concentrates derived from a patient’s own blood have been utilized as a regenerative strategy in recent years. In the present study, a novel liquid platelet formulation prepared without the use of anti-coagulants (injectable-platelet-rich fibrin, i-PRF) was compared to standard platelet-rich plasma (PRP) with gingival fibroblasts cultured on smooth and roughened titanium implant surfaces. Standard PRP and i-PRF (centrifuged at 700 rpm (60× g) for 3 min) were compared by assays for fibroblast biocompatibility, migration, adhesion, proliferation, as well as expression of platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), collagen1 (COL1) and fibronectin (FN). The results demonstrate that i-PRF induced significantly higher cell migration, as well as higher messenger RNA (mRNA) levels of PDGF, TGF-β, collagen1 and fibronectin when compared to PRP. Furthermore, collagen1 synthesis was highest in the i-PRF group. These findings demonstrate that liquid platelet concentrates can be formulated without the use of anticoagulants and present much translational potential for future research. Future animal and clinical trials are now necessary to further investigate the potential of utilizing i-PRF for soft tissue regenerative protocols in combination with various biomaterials.
Platelet-rich fibrin (PRF) is a blood concentrate derived from venous blood that is processed without anticoagulants by a one-step centrifugation process. This three-dimensional scaffold contains inflammatory cells and plasma proteins entrapped in a fibrin matrix. Liquid-PRF was developed based on the previously described low-speed centrifuge concept (LSCC), which allowed the introduction of a liquid-PRF formulation of fibrinogen and thrombin prior to its conversion to fibrin. Liquid-PRF was introduced to meet the clinical demand for combination with biomaterials in a clinically applicable and easy-to-use way. The aim of the present study was to evaluate, ex vivo, the interaction of the liquid-PRF constituents with five different collagen biomaterials by histological analyses. The results first demonstrated that large variability existed between the biomaterials investigated. Liquid-PRF was able to completely invade Mucograft® (MG; Geistlich Biomaterials, Wolhusen, Switzerland) and to partly invade Bio-Gide® (BG; Geistlich Biomaterials, Wolhusen, Switzerland) and Mucoderm® (MD; Botiss Biomaterials, Berlin, Germany), and Collprotect® (CP; Botiss Biomaterials, Berlin, Germany) showed only a superficial interaction. The BEGO® collagen membrane (BCM; BEGO Implant Systems) appeared to be completely free of liquid-PRF. These results were confirmed by the different cellular penetration and liquid-PRF absorption coefficient (PAC) values of the evaluated membranes. The present study demonstrates a system for loading biomaterials with a complex autologous cell system (liquid-PRF) in a relatively short period of time and in a clinically relevant manner. The combination of biomaterials with liquid-PRF may be clinically utilized to enhance the bioactivity of collagen-based biomaterials and may act as a biomaterial-based growth factor delivery system.
Resorbable synthetic scaffolds are promising for different indications, espe- cially in the context of bone regeneration. However, they require additional biological components to enhance their osteogenic potential. In addition to different cell types, autologous blood-derived matrices offer many advantages to enhance the regenerative capacity of biomaterials. The present study aimed to analyze whether biologization of a PCL-mesh coated using differently centrifuged Platelet rich fibrin (PRF) matrices will have a positive influence on primary human osteoblasts activity in vitro. A polymeric resorbable scaffold (Osteomesh, OsteoporeTM (OP), Singapore) was combined with differently centrifuged PRF matrices to evaluate the additional influence of this biologization concept on bone regeneration in vitro. Peripheral blood of three healthy donors was used to gain PRF matrices centrifuged either at High (710× g, 8 min) or Low (44× g, 8 min) relative centrifugal force (RCF) according to the low speed centrifugation concept (LSCC). OP-PRF constructs were cultured with pOBs. POBs cultured on the uncoated OP served as a control. After three and seven days of cultivation, cell culture supernatants were collected to analyze the pOBs activity by determining the concentrations of VEGF, TGF-β1, PDGF, OPG, IL-8, and ALP- activity. Immunofluorescence staining was used to evaluate the Osteopontin expression of pOBs. After three days, the group of OP+PRFLow+pOBs showed significantly higher expression of IL-8, TGF-ß1, PDGF, and VEGF compared to the group of OP+PRFHigh+pOBs and OP+pOBs. Similar results were observed on day 7. Moreover, OP+PRFLow+pOBs exhibited significantly higher activity of ALP compared to OP+PRFHigh+pOBs and OP+pOBs. Immunofluorescence staining showed a higher number of pOBs adherent to OP+PRFLow+pOBs compared to the groups OP+PRFHigh+pOBs and OP+pOBs. To the best of our knowledge, this study is the first to investigate the osteoblasts activity when cultured on a PRF-coated PCL-mesh in vitro. The presented results suggest that PRFLow centrifuged according to LSCC exhibits autologous blood cells and growth factors, seem to have a significant effect on osteogenesis. Thereby, the combination of OP with PRFLow showed promising results to support bone regeneration. Further in vivo studies are required to verify the results and carry out potential results for clinical translation.
Introduction: The aim of this study was to clinically assess the capacity of a novel bovine pericardium based, non-cross linked collagen matrix in root coverage.
Methods: 62 gingival recessions of Miller class I or II were treated. The matrix was adapted underneath a coronal repositioned split thickness flap. Clinical values were assessed at baseline and after six months.
Results: The mean recession in each patient was 2.2 mm at baseline. 6 Months after surgery 86.7% of the exposed root surfaces were covered. On average 0,3 mm of recession remained. The clinical attachment level changed from 3.5 ± 1.3 mm to 1,8 ( ± 0,7) mm during the observational time period. No statistically significant difference was found in the difference of probing depth. An increase in the width of gingiva was significant. With a baseline value of 1.5 ± 0.9 mm an improvement of 2.4 ± 0.8 mm after six month could be observed. 40 out of 62 recessions were considered a thin biotype at baseline. After 6 months all 62 sites were assessed thick.
Conclusions: The results demonstrate the capacity of the bovine pericardium based non-cross linked collagen matrix for successful root coverage. This material was able to enhance gingival thickness and the width of keratinized gingiva. The percentage of root coverage achieved thereby is comparable to existing techniques. This method might contribute to an increase of patient's comfort and an enhanced aesthetical outcome.
The permeability and inflammatory tissue reaction to Mucomaix® matrix (MM), a non- cross-linked collagen-based matrix was evaluated in both ex vivo and in vivo settings. Liquid platelet rich fibrin (PRF), a blood concentrate system, was used to assess its capacity to absorb human proteins and interact with blood cells ex vivo. In the in vivo aspect, 12 Wister rats had MM implanted subcutaneously, whereas another 12 rats (control) were sham-operated without biomaterial implantation. On days 3, 15 and 30, explantation was completed (four rats per time-point) to evaluate the tissue reactions to the matrix. Data collected were statistically analyzed using analysis of variance (ANOVA) and Tukey multiple comparisons tests (GraphPad Prism 8). The matrix absorbed the liquid PRF in the ex vivo study. Day 3 post-implantation revealed mild tissue inflammatory reaction with presence of mononuclear cells in the implantation site and on the biomaterial surface (mostly CD68-positive macrophages). The control group at this stage had more mononuclear cells than the test group. From day 15, multinucleated giant cells (MNGCs) were seen in the implantation site and the outer third of the matrix with marked increase on day 30 and spread to the matrix core. The presence of these CD68-positive MNGCs was associated with significant matrix vascularization. The matrix degraded significantly over the study period, but its core was still visible as of day 30 post-implantation. The high permeability and fast degradation properties of MM were highlighted.
Background: With the aging population and a rising incidence of squamous cell carcinoma of the head and neck (SCCHN), there is an emerging need for developing strategies to treat elderly patients.
Patients and Methods: We retrospectively analyzed 158 patients treated with definitive, concurrent chemoradiotherapy (CRT) for SCCHN. Clinicopathological characteristics, acute toxicities, and oncological outcomes were compared between patients younger and older than (or of age equal to) 65, 70, and 75 years.
Results: RT dose, chemotherapy regimen, and total chemotherapy dose were balanced between the groups. After a median follow-up of 29 months, overall survival (OS), progression-free survival (PFS), local control rate, and distant metastasis-free survival stratified by age of ≥65, ≥70, or ≥75 years revealed no differences. The rate of acute toxicities was also not higher for older patients. Worse ECOG performance score (ECOG 2-3) was associated with impaired OS () and PFS ().
Conclusion: Definitive treatment with CRT for SCCHN is feasible and effective; even in advanced age treatment decisions should be made according to general condition and comorbidity, rather than calendar age alone.
The article “Integrity of dural closure after autologous platelet rich fibrin augmentation: an in vitro study”, written by Vasilikos, I., Beck, J., Ghanaati, S., Grauvogel, J., Nisyrios, T., Grapatsas, K., and Hubbe, U., was originally published Online First without Open Access. After publication in volume 162, issue 4, page 737–743 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0. Open access funding enabled and organized by Projekt DEAL.
Background and Purpose: This review aims to provide a comprehensive overview of the literature and elucidate open questions for future clinical trials concerning diagnostics and treatment modalities for cervical cancer of unknown primary (CUP).
Methods: A literature search for head and neck CUP was performed with focus on diagnostics and therapies as well as molecular markers.
Results: High level evidence on CUP is limited. However, it seems that a consensus exists regarding the optimal diagnostic procedures. The correct implementation of biomarkers for patient stratification and treatment remains unclear. An even greater dispute dominates about the ideal treatment with publications ranging from sole surgery to surgery with postoperative bilateral radiotherapy with inclusion of the mucosa and concomitant chemotherapy.
Conclusions: Cervical CUP represents a very heterogeneous malignant disease. On this account many aspects concerning treatment optimization remain unclear, despite a considerable number of publications in the past. Future research in form of prospective randomized trials is needed in order to better define patient stratification criteria and enable tailored treatment.