Potential antibacterial activity and healing effect of topical administration of bone marrow and adipose mesenchymal stem cells encapsulated in collagen-fibrin hydrogel scaffold on full-thickness burn wound infection caused by Pseudomonas aeruginosa.

Burns injuries are prone to hospital-acquired infections, and Pseudomonas aeruginosa is one of the most common causes of mortality and morbidity in patients with burn injuries. Thus, this study aimed to analyze the effects of topical treatment with bone marrow (BM-MSC) and adipose mesenchymal stem cells (AD-MSC) encapsulated in collagen and fibrin scaffolds in a Balb/c model of burn wound infection. Extraction of stem cells from adipose and bone marrow tissue of rats was performed and cells were characterized using standard methods. Then, collagen, fibrin and collagen-fibrin scaffolds were constructed and the extracted cells were encapsulated in all three scaffolds. Then, 3rd degree burn was induced in mice and 1.5 × 108 (CFU/ml) of P. aeruginosa was introduced to the burn wound. Subsequently, after 24 h of inducing wound infection, encapsulated MSCs were introduced as dressings to burn wound infection and microbial load as well as rate of wound infection healing was measured. The results of this study showed that the use of BM-MSC and AD-MSC encapsulated in collagen-fibrin scaffold reduced the bacteria load down to 54 and 21 CFU/gr, respectively (P < 0.05). Moreover, BM-MSC and AD-MSC encapsulated in collagen-fibrin showed 80% and 75% wound healing, respectively (P < 0.05). Also, we found no significant between cell origin and healing. Encapsulation of MSCs into collagen-fibrin scaffolds could be effective not only against P. aeruginosa infection, but also healing and regeneration of burn wound.

Fibrin-based haemostatic agents for reducing blood loss in adult liver resection.

BACKGROUND: Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use. OBJECTIVES: To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science up to 20 January 2023. We also searched online trial registries, checked the reference lists of all primary studies, and contacted the authors of included trials for additional published or unpublished trials. SELECTION CRITERIA: We considered for inclusion all randomised clinical trials evaluating FBHAs versus no topical intervention or non-FBHAs, irrespective of publication type, publication status, language of publication, and outcomes reported. Eligible participants could have any liver pathology and be undergoing major or minor liver resections through open or laparoscopic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the literature search and used data extraction forms to collate the results. We expressed dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences (MDs), each with their corresponding 95% confidence interval (CI). We used a random-effects model for the main analyses. Our primary outcomes were perioperative mortality, serious adverse events, haemostatic efficacy, and health-related quality of life. Our secondary outcomes were efficacy as sealant, adverse events considered non-serious, operating time, and length of hospital stay. We assessed the certainty of the evidence with GRADE and presented results in two summary of findings tables. MAIN RESULTS: We included 22 trials (2945 participants) evaluating FBHAs versus no intervention or non-FBHAs; 19 trials with 2642 participants provided data for the meta-analyses. Twelve trials reported commercial funding, one trial reported no financial support, and nine trials provided no information on funding. Below we present the most clinically relevant outcome results, also displayed in our summary of findings table. Fibrin-based haemostatic agents versus no intervention Six trials (1001 participants) compared FBHAs with no intervention. One trial was at low risk of bias in all five domains, and all other trials were at high or unclear risk of bias in at least one domain. Two trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58, 95% CI 0.89 to 7.44; 4 trials, 782 participants), serious adverse events (RR 0.96, 95% CI 0.88 to 1.05; 4 trials, 782 participants), postoperative transfusion (RR 1.04, 95% CI 0.77 to 1.40; 5 trials, 864 participants), reoperation (RR 2.92, 95% CI 0.58 to 14.61; 2 trials, 612 participants), or postoperative bile leak (RR 1.00, 95% CI 0.67 to 1.48; 4 trials, 782 participants), as the certainty of evidence was very low for all these outcomes. Fibrin-based haemostatic agents versus non-fibrin-based haemostatic agents Sixteen trials (1944 participants) compared FBHAs with non-FBHAs. All trials had at least one domain at high or unclear risk of bias. Twelve trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03, 95% CI 0.62 to 1.72; 11 trials, 1436 participants), postoperative transfusion (RR 0.92, 95% CI 0.68 to 1.25; 7 trials, 599 participants), reoperation (RR 0.48, 95% CI 0.25 to 0.90; 3 trials, 358 participants), or postoperative bile leak (RR 1.15, 95% CI 0.60 to 2.21; 9 trials, 1115 participants), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99, 95% CI 0.95 to 1.03; 9 trials, 1176 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.

Plasma-Rich Fibrin-Regenerative Material in Tympanic Membrane Surgery.

Background and Objectives: Platelet-rich fibrin (PRF) membrane plays an important role in cell proliferation and aids in healing. This study aimed to assess the safety and efficacy of the addition of PRF to the graft in tympanoplasty. Materials and Methods: A retrospective study was conducted involving 47 patients with chronic dry eardrum perforation, who were candidates for different types of tympanoplasty (type I-IV). The study took place in the ENT department, County Emergency Clinical Hospital of Cluj-Napoca. In group 1 (27 patients) tympanoplasty was performed with a cartilage graft, while in group 2 (20 patients) a cartilage graft was used with the addition of a PRF membrane. The PRF clot was extracted and transformed into a thin membrane. Postoperative evaluation included otoendoscopy and otomicroscopy at 1, 3, 6, and 12 months after surgery, as well as pure-tone audiometry at 12 months. Results: Postoperative follow-up at 1, 3, 6, and 12 months showed a higher rate of graft survival in the PRF group than in the non-PRF group. At the 12-month mark, a successful outcome was observed in 95.0% of patients in the PRF group, while the success rate in group 1 was 70.4% (p < 0.05). The postoperative hearing threshold value was statistically significantly lower in the group with PRF, compared to the non-PRF group, being 18.4 ± 10.4 dB and 27.6 ± 16.2 dB (p < 0.001), respectively. Although the postoperative air-bone gap value did not differ significantly between groups, there was a greater improvement in the PRF group (p < 0.7). The PRF was well tolerated, and the incisions healed perfectly. Conclusions: The PRF membrane increases the rate of autograft survival and is therefore an effective material for patients with chronic perforations of the tympanic membrane.

Cicatrization of oncological wounds by autologous fibrin biopolymer dressing treatment: a case series.

INTRODUCTION: Traditional therapies used to treat chronic wounds are often expensive and, in general, are not adequate to support healing. A promising alternative to conventional dressings is the autologous biopolymer FM, full of cytokines and growth factors that accelerate the healing process of wounds of various etiologies. MATERIALS AND METHODS: The authors report 3 cases in which FM was used to treat chronic oncological wounds that had been conventionally treated for more than 6 months with no sign of healing. RESULTS: Among the 3 reported cases, there was complete healing of 2 wounds. The other lesion did not heal, mainly due to the location (at the base of the skull). However, it significantly reduced its area, extension, and depth. No adverse effects or hypertrophic scar formation were recorded, and the patients reported an absence of pain from the second week of FM application. CONCLUSIONS: The proposed FM dressing approach was effective in healing and speeding up tissue regeneration. It can also be considered one of the most versatile delivery systems to the wound bed, as it is an excellent carrier of growth factors and leukocytes.

Comparative histological evaluation of two PRF formulations (PRF High and PRF Medium) on quality of life and healing outcome of apicomarginal defects: A randomized clinical trial.

The objective of this randomized clinical trial was to investigate the effects of two PRF formulations (PRF High and PRF Medium) on quality of life and healing outcome (2D and 3D) of apicomarginal defects. Patients presenting with endodontic lesions and concomitant periodontal communication were randomly allocated to PRF High and PRF Medium groups. The treatment protocol in each group included a periapical surgical procedure with placement of PRF clot and membrane in the bony defect and on the denuded root surface, respectively. Quality of life was assessed for 1 week after surgery following a modified version of the patient's perception questionnaire. Postoperative pain was assessed using a visual analog scale. Clinical and radiographic evaluations were performed using Rud and Molven 2D criteria and Modified PENN 3D criteria. Buccal bone formation was assessed using sagittal and corresponding axial sections in CBCT. Histological analysis was performed using hematoxylin and eosin (H and E) staining and attaching primary antibodies to tissue sections. In total, 40 patients were enrolled in the trial (N = 20 per group). PRF Medium group patients reported significantly less swelling on the 1st (p = 0.036), 2nd (p = 0.034), and 3rd (p = 0.023) days, and average pain on the 2nd (p = 0.031), 3rd (p = 0.03), and 4th (p = 0.04) days postoperatively. The difference in success rate for periapical healing was non-significant between the PRF Medium group (89.5%) and PRF High group (90%), in both 2D and 3D imaging (p = 0.957). The formation of buccal bone was observed in five cases (26.3%) and four cases (20%) in the PRF Medium and PRF High groups, respectively, with a non-significant difference (p = 0.575). PRF Medium clots had a loose fibrin structure with a significantly higher number of neutrophils (473.79 ± 82.89 per mm2) than PRF High clots, which had a dense structure and fewer neutrophils (253.15 ± 63.86 per mm2) (p = 0.001). Autologous platelet concentrates (APCs) promoted satisfactory periapical healing, with no significant difference between the groups. Within the limitations of the study, it seems that PRF Medium should be preferred over PRF High when the patients' quality of life is the priority.

Effectiveness of Plasma-Rich Fibrin and De-Epithelialized Free Gingival Graft in the Treatment of Gingival Recessions.

Introduction/Aim: Soft tissue dehiscences such as gingival recessions are a very common problem that we face in modern periodontics. This clinical study aimed to analyze the effectiveness of surgical procedures using a de-epithelialized gingival graft (DGG) combined with a coronally advanced flap and to evaluate the application of plasma-rich fibrin (PRF). Methods: The study included 40 teeth (20 patients) with Miller class I and II gingival recessions. Twenty recessions (20 patients) were treated utilizing the de-epithelialized gingival graft in combination with the coronally advanced flap, and on the opposite side of the jaw, the same number of recessions were treated utilizing plasma-rich fibrin combined with the coronally advanced flap. To evaluate tissue condition and the clinical parameters before and after the surgical procedure, the following parameters were used: the degree of epithelial attachment (DEA), the width of keratinized gingiva (WKG), and the vertical depth of recession (VDR). Results: based on the achieved results and the analysis of clinical parameters, a statistically significant reduction in the vertical depth of recession was proven in both groups, with very similar mean percentages of root coverage, with the difference being that the stability of the soft tissues of the treated region was more visible in the DGG. Conclusion: using modern surgical procedures allows the regeneration of not only the soft tissues but also deeper periodontal tissues.

Tissue Bioengineering with Fibrin Scaffolds and Deproteinized Bone Matrix Associated or Not with the Transoperative Laser Photobiomodulation Protocol.

Extending the range of use of the heterologous fibrin biopolymer, this pre-clinical study showed a new proportionality of its components directed to the formation of scaffold with a lower density of the resulting mesh to facilitate the infiltration of bone cells, and combined with therapy by laser photobiomodulation, in order to accelerate the repair process and decrease the morphofunctional recovery time. Thus, a transoperative protocol of laser photobiomodulation (L) was evaluated in critical bone defects filled with deproteinized bovine bone particles (P) associated with heterologous fibrin biopolymer (HF). The groups were: BCL (blood clot + laser); HF; HFL; PHF (P+HF); PHFL (P+HF+L). Microtomographically, bone volume (BV) at 14 days, was higher in the PHF and PHFL groups (10.45 ± 3.31 mm3 and 9.94 ± 1.51 mm3), significantly increasing in the BCL, HFL and PHFL groups. Histologically, in all experimental groups, the defects were not reestablished either in the external cortical bone or in the epidural, occurring only in partial bone repair. At 42 days, the bone area (BA) increased in all groups, being significantly higher in the laser-treated groups. The quantification of bone collagen fibers showed that the percentage of collagen fibers in the bone tissue was similar between the groups for each experimental period, but significantly higher at 42 days (35.71 ± 6.89%) compared to 14 days (18.94 ± 6.86%). It can be concluded that the results of the present study denote potential effects of laser radiation capable of inducing functional bone regeneration, through the synergistic combination of biomaterials and the new ratio of heterologous fibrin biopolymer components (1:1:1) was able to make the resulting fibrin mesh less dense and susceptible to cellular permeability. Thus, the best fibrinogen concentration should be evaluated to find the ideal heterologous fibrin scaffold.

Efficacy of fibrin-rich platelets and leukocytes (L-PRF) in tissue repair in surgical oral procedures in patients using zoledronic acid-case-control study.

INTRODUCTION: Medication-related osteonecrosis of the jaws (MRONJ) is a complication that develops in patients who use or have used antiresorptive or antiangiogenic medications for the treatment of bone metabolic disease and bone metastases. Clinically, MRONJ is characterized by the appearance of an inflammation in soft tissues and exposure of necrotic bone tissue in mandible or maxilla, for a period of 8 weeks, in patients with no history of head and neck radiotherapy that were being or are being treated with antiresorptive and/or antiangiogenic agents. The fibrin-rich platelets and leukocytes (L-PRF) membrane has been used as an alternative for MRONJ prevention. The aim of this study was to evaluate the use of L-PRF in prevention and treatment of bone necrosis. MATERIAL AND METHODS: The patients included had MRONJ diagnosis confirmed after clinical and radiographic examination and patients whose only therapeutic option was dental extraction. RESULTS: Twenty patients were included in the study and were divided in three groups. Two patients were removed from the study due to previous history of pentoxifylline and tocopherol use. The result of surgical treatment was successful in 57% in group 1 (control/MRONJ prevention), 100% in group 2 (MRONJ prevention), and 80% in group 3 (MRONJ treatment). CONCLUSION: L-PRF is an autologous biomaterial that allows the release of growth factors for a prolonged time, resulting in a better healing, reducing the risk contamination, edema, and postoperative pain, being a great ally in the prevention and treatment of MRONJ because it returns to these patients, mainly quality of life, reducing pain, and recurrent infections commonly seen in the processes of bone necrosis of the jaws.

Tissue factor-induced fibrinogenesis mediates cancer cell clustering and multiclonal peritoneal metastasis.

Peritoneal metastasis is one of the most frequent causes of death in several types of advanced cancers; however, the underlying molecular mechanisms remain largely unknown. In this study, we exploited multicolor fluorescent lineage tracking to investigate the clonality of peritoneal metastasis in mouse xenograft models. When peritoneal metastasis was induced by intraperitoneal or orthotopic injection of multicolored cancer cells, each peritoneally metastasized tumor displayed multicolor fluorescence regardless of metastasis sites, indicating that it consists of multiclonal cancer cell populations. Multicolored cancer cell clusters form within the peritoneal cavity and collectively attach to the peritoneum. In vitro, peritoneal lavage fluid or cleared ascitic fluid derived from cancer patients induces cancer cell clustering, which is inhibited by anticoagulants. Cancer cell clusters formed in vitro and in vivo are associated with fibrin formation. Furthermore, tissue factor knockout in cancer cells abrogates cell clustering, peritoneal attachment, and peritoneal metastasis. Thus, we propose that cancer cells activate the coagulation cascade via tissue factor to form fibrin-mediated cell clusters and promote peritoneal attachment; these factors lead to the development of multiclonal peritoneal metastasis and may be therapeutic targets.

Effect of leukocyte-platelet fibrin-rich wound reconstruction followed by full-thickness skin grafting in the treatment of diabetic foot Wagner grade 4 ulcer gangrene (toe area).

This study investigated the effect of L-PRF on promoting full-thickness skin grafting for the treatment of diabetic foot ulcer wounds and attempted to characterize the mechanism. In a retrospective study, we centrifugated 10-20 ml of venous blood at 1006.2 g for 20 min. The fibrin clot between the top oligocellular plasma layer and the bottom erythrocyte layer was extracted and directly used, without compression, to cover the wound after debridement. Patients who received L-PRF before skin grafting underwent surgery earlier than patients in the control group. Skin necrosis occurred in 7 patients (28%) in the L-PRF group and 16 (64%) in the control group. The difference was statistically significant, P < .05. The postoperative infection rate in the control group (56%) was significantly higher than that in the L-PRF group (24%), P < .05. During a mean follow-up of 1 year, ulcer recurrence occurred in 9 patients (36%) in the control group compared with 4 patients (16%) in the L-PRF group, P < .05. The final amputation rate was also higher in the control group (48%) than in the L-PRF group (20%). The difference is statistically significant, P < .05. The Maryland scale score and SF-36 score of the two groups of patients after treatment were significantly better than those before treatment, and the difference was statistically significant (P < .05). The L-PRF group (94.80 ± 4.14) had better foot scores at the last follow-up after treatment than the control group (88.84 ± 5.22) (P < .05). The results showed that L-PRF played a positive role in the treatment of Wagner grade 4 ulcer gangrene with free full-thickness skin grafts.

What is the context?● Diabetic foot is a serious complication in the later stage of the disease course of diabetic patients. The incidence rate is increasing year by year. In severe cases, it can lead to amputation or even death.● For diabetic ulcer wounds, dressings such as L-PRF or autologous fat are often used in the initial stage to speed up wound healing. For advanced wounds, especially patients with local tissue gangrene, simple wound dressings cannot meet the needs of wounds. People often use skin flaps or different types of skin grafts to treat advanced wounds.● Flap or skin grafting has been shown to be effective, but because of the patient's own neurovascular injury and infection, the rate of graft necrosis and ulcer recurrence is extremely high. What is new?● This study discusses the treatment of advanced wounds in diabetes. After thorough debridement and before skin grafting, we first covered the wound with L-PRF and observed the wound condition. Studies have shown that the use of L-PRF can allow the original poor wound to be reconstructed: the content of growth factors and growth-related cells is increased, blood circulation is improved and granulation tissue growth, bone and tendon exposure is improved, and infection is controlled. What is the impact?● This study provides evidence that using L-PRF to reconstruct wounds can greatly shorten the preparation time for elective surgery. Reconstructed wounds can better accept free skin grafts, and the incidence of postoperative complications and amputation (particularly, toe amputation) is also lower.

A single dose of benzathine penicillin G as an effective treatment for malignant syphilis in an HIV-positive patient: a case report.

Malignant syphilis (MS) is a rare, atypical manifestation of secondary syphilis. Ulcerative lesions should be suspected as MS when found with supporting microscopic morphology, a high syphilis serology titer test, a Jarisch-Herxheimer reaction (JHR), and rapid disease resolution. To date, there is no specific recommendation for treatment for MS. A 24-year-old HIV-positive MSM patient with a CD4 count of 470 cells/µl presented with a chief complaint of necrotic, ulcerative lesions and oyster shell-like surface plaques on his face, trunk, groin, and extremities. The patient also developed various typical presentations of secondary syphilis. Dark-field microscopy revealed spirochetes. Histopathological examination showed spongiotic dermatitis with many neutrophil cells in the dermis, together with endarteritis and fibrin micro-thrombus in the blood vessels. The patient had a high venereal disease research laboratory (VDRL) titer of 1:512. There was rapid disease resolution following a single injection of 2,400,000-unit benzathine penicillin G (BPG); together with anti-retroviral therapy, this was supportive treatment for MS. JHR was not observed in this study and many other reports. This case showed that ulcerative lesions with an oyster shell-like surface presenting in HIV-positive patients along with supporting microscopic morphology, high VDRL titer, and a dramatic improvement after antibiotic treatment is highly suggestive of MS. JHR may no longer be a characteristic of MS. A single dose of 2,400,000-unit BPG is sufficient for MS treatment.

Exploring the Fibrin(ogen)olytic, Anticoagulant, and Antithrombotic Activities of Natural Cysteine Protease (Ficin) with the κ-Carrageenan-Induced Rat Tail Thrombosis Model.

Although fibrinolytic enzymes and thrombolytic agents help in cardiovascular disease treatment, those currently available have several side effects. This warrants the search for safer alternatives. Several natural cysteine protease preparations are used in traditional medicine to improve platelet aggregation and thrombosis-related diseases. Hence, this study aimed to investigate the effect of ficin, a natural cysteine protease, on fibrin(ogen) and blood coagulation. The optimal pH (pH 7) and temperature (37 °C) for proteolytic activity were determined using the azocasein method. Fibrinogen action and fibrinolytic activity were measured both electrophoretically and by the fibrin plate assay. The effect of ficin on blood coagulation was studied by conventional coagulation tests: prothrombin time (PT), activated partial thromboplastin time (aPTT), blood clot lysis assay, and the κ-carrageenan thrombosis model. The Aα, Bß, and γ bands of fibrinogen are readily cleaved by ficin, and we also observed a significant increase in PT and aPTT. Further, the mean length of the infarcted regions in the tails of Sprague-Dawley rats was shorter in rats administered 10 U/mL of ficin than in control rats. These findings suggest that natural cysteine protease, ficin contains novel fibrin and fibrinogenolytic enzymes and can be used for preventing and/or treating thrombosis-associated cardiovascular disorders.

Efficacy and Safety of Concentrated Growth Factors and Platelet- Rich Fibrin on Stability and Bone Regeneration in Patients with Immediate Dental Implants: A Randomized Controlled Trial.

PURPOSE: Immediate dental implants revolutionized the field of implant dentistry with significant advantages over conventional implants. The lack of adequate bone in the extraction socket raises the question of the appropriate timing of implant loading. Platelet concentrates have been used widely to accelerate bone regeneration in the maxillofacial region. This study evaluates the effect of platelet concentrates on bone healing and implant stability in the maxillary and mandibular molar regions. Bone regeneration is regulated by several growth factors, particularly vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1); therefore, quantification of these factors in platelet concentrates and its correlation with bone healing has been assessed in this study. MATERIALS AND METHODS: The primary aim of this randomized clinical trial was to compare the stability of immediate dental implants in the maxillary and mandibular molar regions treated with platelet-rich fibrin (PRF) versus concentrated growth factors (CGF) using resonance frequency analysis (RFA). The secondary objectives were to evaluate the bone regenerate around implants with the use of PRF and CGF and to quantify growth factors VEGF and TGF-ß1 in the prepared CGF and PRF and their correlation with bone healing, if any. A total of 36 patients were randomized into three groups (12 each): control, PRF, and CGF. In all patients, immediate implants were placed either with or without platelet concentrate (PRF or CGF). Implant stability was measured using RFA immediately postoperatively and at 4, 8, and 12 or 16 weeks (12 weeks for mandible and 16 weeks for maxilla) postoperatively. Radiodensity and the bone gap (horizontal/vertical) were measured on intraoral periapical radiographs immediately postoperatively and at 8 weeks and 12 or 16 weeks postoperatively. RESULTS: On comparing the implant stability quotient (ISQ), radiodensity/grayscale (GS), and horizontal and vertical bone gap (HG and VG), there was no significant difference noted between the three groups at any point in time. On ISQ analysis at 8 weeks, the control group showed a significant improvement (P = .04), whereas at 12 or 16 weeks, significant improvement was seen in PRF (P = .03) and CGF groups (P = .02). In GS assessment, only the control group showed significant improvement at 12 or 16 weeks (P = .009). In horizontal and vertical bone gap analysis all three groups showed significant improvement at 8 weeks (control [P < .001], PRF [P = .001], CGF [P = .01]) as well as 12 or 16 weeks (control [P < .001], PRF [P < .001], CGF [P = .006]). The enzyme-linked immunosorbent assay (ELISA) quantification of VEGF and TGF-ß1 showed significant concentration of VEGF in PRF as compared to the plasma, while concentration of TGF-ß1 was found to be comparable in both groups. CONCLUSION: The application of platelet concentrates seems to enhance stability of implants, but intergroup results were nonsignificant at all time points. There was no statistically significant difference between the three groups when comparing quality (radiodensity/grayscale) and quantity (horizontal and vertical gap reduction) of bone regenerate. Studies with larger sample sizes are required to make conclusive assertions regarding efficacy of platelet concentrates in dental implants.

In Situ-Forming Fibrin Gel Encapsulation of MSC-Exosomes for Partial-Thickness Rotator Cuff Tears in a Rabbit Model: Effectiveness Shown in Preventing Tear Progression and Promoting Healing.

BACKGROUND: Current nonoperative treatments for partial-thickness rotator cuff tears (PTRCTs) have limited effectiveness in preventing tear progression or promoting tendon healing. This study aimed to establish a rabbit model using in situ-forming fibrin gel containing adipose stem cell-derived exosomes (ASC-Exos/fibrin) to treat PTRCTs. METHODS: Fifty-six rabbits (112 shoulders) were included in this study and assigned to 4 groups: the control group (32 shoulders; PTRCTs without treatment), the fibrin group (32 shoulders; PTRCTs treated with fibrin gel), the ASC-Exo/fibrin group (32 shoulders; PTRCTs treated with ASC-Exos/fibrin), and the sham group (16 shoulders; sham surgery). Bilateral, 50%-thickness, bursal-side PTRCTs of 1 mm (depth) × 3 mm (width) × 5 mm (length) on the supraspinatus tendon were established by a number-11 scalpel blade, with accuracy of the measurement ensured by a digital vernier caliper. At 6 and 12 weeks postoperatively, gross observation, measurement of the thickness of residual supraspinatus tendons, and histological and biomechanical analyses were performed to analyze tendon repair. RESULTS: At 12 weeks postoperatively, the tendon thickness in the ASC-Exos/fibrin group (mean and standard deviation, 1.63 ± 0.19 mm) was significantly greater than in the control group (0.85 ± 0.09 mm) (p < 0.0001) and fibrin group (1.16 ± 0.17 mm) (p < 0.0001). The histological score in the ASC-Exos/fibrin group (6.25 ± 0.53) was significantly better than in the control group (11.38 ± 0.72) (p < 0.0001) and fibrin group (9.00 ± 0.54) (p < 0.0001). Overall, immunohistochemical staining of types-I and III collagen and biomechanical testing also showed ASC-Exos/fibrin to be more effective in repairing PTRCTs than fibrin alone and no treatment. CONCLUSIONS: Local administration of in situ-forming ASC-Exos/fibrin effectively facilitated the healing of bursal-side PTRCTs in rabbits. This approach may be a candidate for the nonoperative management of PTRCTs. CLINICAL RELEVANCE: Ultrasound-guided injection of ASC-Exos/fibrin may be a novel nonoperative strategy to treat PTRCTs.

Treatment of oroantral communication with Platelet-Rich Fibrin: A systematic review.

BACKGROUND: Oroantral communication (OAC) is the opening between the maxillary sinus and the oral cavity, which constitutes a gate for the mucosal infection in the maxillary sinus. On the other hand, an OAF develops when the OAC does not close spontaneously, remains manifest and is epithelialized. Several methods have been proposed to solve these situations, however, they are associated with increased postoperative morbidity and/or higher associated costs and require some experience of the surgeon to perform them. To overcome these disadvantages, the use of Platelet-Rich Fibrin (PRF) is proposed. The present study aims to perform a systematic review of the literature, collecting cases in which PRF was used in the treatment of OACs/OAFs. MATERIALS AND METHODS: An electronic search of the MEDLINE database (via PubMed) and Web of Science was performed using the following MeSH terms (Medical Subjects Headings): (oroantral communication OR oroantral fistula OR buccosinusal communication) AND (platelet-rich fibrin OR prf OR fibrin mesh). The criteria used were those described by the PRISMA® Statement. The search was not time-restricted and was updated to April 2021. RESULTS: After searching, 11 articles were included that met the established criteria. In these, PRF was used alone or in combination with bi- or trilaminar techniques achieving complete resolution in 100% of cases (n = 116). CONCLUSIONS: With the limitations of this study, it can be established that PRF can be used alone for the treatment of OACs/OAFs up to 5 mm and, in larger defects, it is advisable to combine it with bi- or trilaminar techniques. PRF is an effective therapeutic option, with minimal associated postoperative morbidity compared to other techniques and allows the position of the mucogingival junction to be preserved. Its combination with bone grafting improves the starting point before the replacement of the missing tooth with a dental implant.

Fibrin immobilization vestibular extension (FIVE): A case series.

AIMS: The objective of the present case series is to report on the rationale, surgical technique and outcome of a protocol for peri-implant mucosal phenotype modification therapy, referred to as "fibrin immobilization vestibular extension (FIVE)". MATERIAL AND METHODS: The protocol utilized entailed apical positioning and stabilization of peri-implant flap with modular screws. The screws were also used for the immobilization of solid matrix platelet-rich fibrin to fill the gap created between apically positioned flap and the crestal margin of the flap. RESULTS: A total of 30 patients (12 male, 18 females) with 93 implants were treated with FIVE protocol for various indications, including for vestibular extension following alveolar ridge augmentation (N = 6), preprosthetic (N = 9), postprosthetic (N = 2), and peri-implantitis (N = 13). The keratinized mucosal width preoperatively was 1.67 mm with 95% confidence interval [CI] (1.46, 1.88). Immediately following FIVE surgery, the vestibule was extended to 9.10 with 95% CI (8.44, 9.76). At 3 months, 4.9 mm (95% CI: 4.5-5.2 mm) of peri-implant keratinized mucosal width was present. The keratinized mucosal width remained relatively stable thereafter and was 4.0 mm (95% CI: 3.5-4.5 mm) at 3 years post-FIVE surgery. When overall group means across all time points were analyzed, maxilla had mean of 6.1 mm (95% CI: 5.8-6.5) versus mandible exhibited mean of 5.1 mm (95% CI: 4.6-5.6 mm). The mean of maxilla was significantly higher than that of the mandible (p < 0.0001) across all time points. Treatment of peri-implantitis with FIVE lead to significant pocket reduction and wide band of keratinized mucosa. Seven of 38 implants in 3 of 13 peri-implantitis patients were removed due to advanced peri-implantitis. DISCUSSION: The present case series provides proof-of-principle data for efficacy of FIVE for peri-implant phenotype modification therapy that generated attached keratinized mucosa in a variety of applications. This protocol provides an alternative to procedures involving harvesting of autogenous mucosal graft.

Healing of periodontal intrabony defects following treatment with a new-generation platelet-rich fibrin. / Vérlemezkében gazdag fibrinnel kezelt parodontalis csontdefektusok gyógyulásának értékelése.

Összefoglaló. Az autológ vérlemezke-koncentrátumok az orvoslás egyre több területén kerülnek alkalmazásra. A vérlemezkében gazdag fibrin, ebben a kategóriában, az adott terápiás lehetoségek közül a legaktuálisabb. Elonyei, hogy alvadásgátló hozzáadása nélkül preparálható, egy centrifugálást igényel, és több formában alkalmazható. A vérlemezkében gazdag fibrin újabb generációja további lehetoségeket teremthet, így a parodontalis sebgyógyulás terén is. Az esetek bemutatásának célja parodontalis intraossealis csontdefektusok gyógyulásának rövid távú klinikai értékelése autológ vérlemezkében gazdag készítménnyel (advanced platelet-rich fibrin) történt kezelést követoen. A bemutatott eseteknél preoperatíven, majd 6 hónappal a mutétet követoen történt kiértékelés a következo parodontológiai paraméterek rögzítésével: tasakszondázási mélység (probing depth), illetve klinikai tapadási szint (clinical attachment level). Teljes vastagságú lebenyek képzését követoen a csontdefektus kürettálása, illetve gyökérsimítás történt, majd a preoperatíven preparált, vérlemezkében gazdag fibrin applikálására került sor, melyet sebzárás követett. Fél évvel a sebészi beavatkozás után a szondázási mélység csökkenése és a klinikai tapadási nívó növekedése volt tapasztalható. Bemutatott eseteinknél a vérlemezkében gazdag fibrin applikációja pozitív klinikai eredményeket mutatott a parodontalis sebgyógyulás tekintetében. A vérlemezkében gazdag fibrinnek mint humán autológ preparátumnak a használata elosegítheti a parodontalis defektusok sikeres kezelését. Orv Hetil. 2022; 163(12): 484-490. Summary. Autologous platelet concentrates are being used in more and more areas of medicine. Application of platelet-rich fibrin is the most topical among these therapeutic options. As main advantages, it can be prepared without the addition of anticoagulants, requires only one centrifugation and can be used in various forms. A new generation of platelet-rich fibrin may open up further opportunities, including those in periodontal wound healing. The aim of this case series is to provide a short-term clinical evaluation of the healing of periodontal intrabony defects after treatment with an autologous platelet-rich fibrin product (advanced platelet-rich fibrin). The presented cases were evaluated preoperatively and 6 months after surgery by recording the following periodontal parameters: probing depth and clinical attachment level. After full-thickness flap preparation, intrabony defect curettage, scaling and root planing were performed, followed by the application of preoperatively prepared platelet-rich fibrin and wound closure. Six months after surgery, pocket depth reductions and clinical attachment level gains were observed. In our presented cases, the platelet-rich fibrin application showed positive clinical results regarding periodontal wound healing and may facilitate the successful treatment of periodontal defects. Orv Hetil. 2022; 163(12): 484-490.

Autologous Cultured Bone Marrow-Derived Mesenchymal Stem Cells in a Fibrin Spray to Treat Venous Ulcers: A Randomized Controlled Double-Blind Pilot Study.

We treated a small cohort of venous ulcers that were very unresponsive to standard and advanced therapies with autologous cultured bone marrow-derived mesenchymal stem cells (MSCs). This pilot clinical trial was randomized, controlled, and double-blinded. Subjects were treated with either normal saline (Group A), fibrin spray alone (Group B), or MSCs in fibrin (1 million cells/cm2 of wound bed surface) (Group C). The control and test materials were applied to the wound using a double-barreled syringe with thrombin and fibrinogen (with or without MSCs) in each barrel, or saline alone in both barrels. The MSCs were separated, cultured in vitro, and expanded in a dedicated Good Manufacturing Practice (GMP) facility from 30-50 ml of bone marrow aspirate obtained from the iliac crest in Group C subjects. To ensure that the study remained controlled and blinded, subjects who were randomized to one of the two control arms (saline or fibrin) underwent sham bone marrow aspiration performed by a hematologist who anesthetized the iliac crest area down to and pushing against the periosteum, but without penetrating the bone marrow. Therefore, both the clinician who evaluated wound progress and the study subjects had no knowledge of whether bone aspiration was actually performed and what treatment had been applied to the wound. The study was performed after full FDA investigational new drug (IND) approval. The primary endpoint was the rate of healing (wound closure as linear healing from the wound margins in cm/week), as measured by the Gilman equation. One-way ANOVA was used to calculate the statistical significance of differences between the mean healing rates of each of the 3 treatment groups every 4 weeks and over the 24 weeks of treatment. Overall, treatment with MSCs accelerated the healing rate by about 10-fold compared to those in the saline and fibrin control groups. Although the total number of patients in this pilot study was small (n=11), the statistical significance was surprisingly promising: p<0.01 and f-ratio of 15.9358. No serious adverse events were noted. This small but carefully performed prospective, controlled, randomized, and double-blinded pilot study in a rare population of totally unresponsive patients adds to previous reports showing the promise of MSCs in the treatment of chronic wounds and provides proof of principle for how to approach this type of very demanding clinical and translational research.

Should patients with non-muscle-invasive bladder cancer discontinue fibrin clot inhibitors during bacille Calmette-Guérin?

OBJECTIVE: To determine the impact of fibrin clot inhibitor (FCI) use on oncological outcomes in a large contemporary cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adequate bacille Calmette-Guérin (BCG). PATIENTS AND METHODS: We performed an Institutional Review Board-approved review of patients with NMIBC treated with adequate intravesical BCG, at our institution between 2000 and 2018. FCI use at the time of BCG therapy was recorded for each patient. Patients were stratified according to use of FCI medication. Recurrence- and progression-free survival were analysed using Kaplan-Meier methods and Cox proportional hazard models. RESULTS: Overall, 226 of 526 patients (43.0%) used a FCI: aspirin (205), clopidogrel (38), warfarin (18) and novel oral anticoagulant (NOAC; seven). The use of FCIs did not adversely affect either recurrence- or progression-free survival (P = 0.385 and P = 0.131, respectively). These results did not change when the impact of aspirin, clopidogrel or warfarin/NOAC use on recurrence and progression was evaluated separately. On multivariate analysis, FCI use was neither associated with tumour recurrence nor progression. CONCLUSION: The use of FCIs was not associated with adverse oncological outcomes in a large contemporary cohort of patients receiving adequate intravesical BCG for NMIBC. Based on these results, FCIs may be safely continued during BCG immunotherapy.

Biochemical Characteristics and Clinical Result of Bone Marrow-Derived Fibrin Clot for Repair of Isolated Meniscal Injury in the Avascular Zone.

PURPOSE: To characterize bone marrow aspirate-derived fibrin clot (BMA clot) and evaluate the clinical result of meniscal repair with a BMA clot for isolated meniscal injury in the avascular zone. METHODS: Blood counts of total leukocytes, platelets, and concentrations of basic fibroblast growth factor (bFGF), transforming growth factor ß (TGF-ß), and stromal cell-derived factor 1 (SDF-1) were analyzed with BMA, peripheral blood (PB), BMA clot, and PB clot from 5 patients treated for meniscal repair. In addition, a retrospective analysis of 30 patients with isolated avascular meniscal injuries who underwent repair with a BMA clot was performed to assess rate failure. Avascular meniscal injury was identified as horizontal tear, radial tear, and flap tear. Clinical failure was defined as the presence of 1 or more of Barrett's criteria. Anatomic failure was defined as the existence of equivalent signal intensity to intra-articular fluid along the repair area on follow-up magnetic resonance imaging (MRI). Patients' demographic and clinical data were compared between the overall failure group and the success group. RESULTS: The bFGF, TGF-ß, and SDF-1 levels of BMA clots were more highly concentrated compared with PB clots. The Lysholm scores and meniscal status evaluated by MRI were significantly improved from preoperatively to postoperatively (both P < .001). The Kellgren-Lawrence grading of knee radiographs did not significantly differ pre- and postoperatively (P = .140). Rates of clinical failure, anatomic failure, and retear were 10%, 6.7%, and 3.3%, respectively. The demographic characteristics and surgical and postoperative status did not significantly differ between the overall failure group and the success group. CONCLUSIONS: BMA clots had increased levels of cytokines compared to PB clots. The retrospective analysis revealed that the rates of clinical failure and anatomic failure after meniscal repair with a BMA clot for isolated avascular meniscal injury were 10% and 6.7%, respectively. LEVEL OF EVIDENCE: Level IV, case series.