Heterologous fibrin biopolymer as an emerging approach to peripheral nerve repair: a scoping review.

Nerve injuries present a substantial challenge within the medical domain due to their prevalent occurrence and significant impact. In nerve injuries, a range of physiopathological and metabolic responses come into play to stabilize and repair the resulting damage. A critical concern arises from the disruption of connections at neuromuscular junctions, leading to profound degeneration and substantial loss of muscle function, thereby hampering motor tasks. While end-to-end neurorrhaphy serves as the established technique for treating peripheral nerve injuries, achieving comprehensive morphofunctional recovery remains a formidable challenge. In pursuit of enhancing the repair process, alternative and supportive methods are being explored. A promising candidate is the utilization of heterologous fibrin biopolymer, a sealant devoid of human blood components. Notably, this biopolymer has showcased its prowess in establishing a stable and protective microenvironment at the site of use in multiple scenarios of regenerative medicine. Hence, this scoping review is directed towards assessing the effects of associating heterologous fibrin biopolymer with neurorrhaphy to treat nerve injuries, drawing upon findings from prior studies disseminated through PubMed/MEDLINE, Scopus, and Web of Science databases. Further discourse delves into the intricacies of the biology of neuromuscular junctions, nerve injury pathophysiology, and the broader utilization of fibrin sealants in conjunction with sutures for nerve reconstruction procedures. The association of the heterologous fibrin biopolymer with neurorrhaphy emerges as a potential avenue for surmounting the limitations associated with traditional sealants while also mitigating degeneration in nerves, muscles, and NMJs post-injury, thereby fostering a more conducive environment for subsequent regeneration. Indeed, queries arise regarding the long-term regenerative potential of this approach and its applicability in reconstructive surgeries for human nerve injuries.

A Novel Fibrin Matrix Derived from Platelet-Rich Plasma: Protocol and Characterization.

Although fibrin matrices derived from Platelet-Rich Plasma (PRP) are widely used in regenerative medicine, they have some limitations that can hinder their application. Modifying the composition of the PRP-derived fibrin matrix may improve its properties, making it suitable for certain medical uses. Three types of fibrin matrices were obtained: a PRP-derived fibrin matrix (FM), a PRP-derived fibrin matrix with a high fibrinogen content and platelets (FM-HFP) and a PRP-derived fibrin matrix with a high fibrinogen content (FM-HF). The fibrinogen levels, biomechanical properties and cell behavior were analyzed. The presence of platelets in the FM-HFP generated an inconsistent fibrin matrix that was discarded for the rest of the analysis. The fibrinogen levels in the FM-FH were higher than those in the FM (p < 0.0001), with a concentration factor of 6.86 ± 1.81. The values of clotting and swelling achieved using the FM-HF were higher (p < 0.0001), with less clot shrinkage (p < 0.0001). The FM had a significantly higher stiffness and turned out to be the most adherent composition (p = 0.027). In terms of cell viability, the FM-HF showed less cell proliferation but higher live/dead ratio values (p < 0.01). The increased fibrinogen and platelet removal in the FM-HF improved its adhesion and other biomechanical properties without affecting cell viability.

The Effect of Platelet-Rich Fibrin and Platelet-Rich Plasma in Secondary Alveolar Bone Grafting in Cleft Lip and Palate Patients: A Systematic Review.

(1) Background: Cleft lip, alveolus, and palate are the most common congenital abnormalities in the world, occurring in one in seven hundred live births. Secondary alveolar bone grafting (SABG) is usually performed when the permanent canine root shows one-half to two-thirds of root development. To improve the surgical outcome, supplemental grafting materials such as platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) have been used as an adjunct. This review is designed to assess the efficacy of PRF and PRP in improving the outcome of SABG. (2) Methods: A comprehensive literature search was performed until 13 October 2022 on MEDLINE, EMBASE, The Cochrane Library, and Pubmed. The full text of potentially relevant studies was reviewed, and only randomised clinical trials (RCTs) were included based on the inclusion criteria. (3) Results: A total of 656 studies were screened, of which four were included for final review. All of the four included studies that evaluated the quantitative or qualitative surgical outcome in varied ways. (4) Conclusions: Results of this review suggest that both PRF or PRP and control group (without the use of PRF/PRP) achieved similar successful outcomes in bone height, bone density, and bone volume in both qualitative and quantitative assessment.

Successful Removal and Replacement of a Stuck Hemodialysis Catheter via Thoracotomy: Report of Two Cases and Literature Review.

Introduction: Stuck tunneled central venous catheters (CVCs) have been increasingly reported. In rare cases, the impossibility of extracting the CVC from the central vein after regular traction is the result of rigid adhesions to the surrounding fibrin sheath. Forced traction during catheter removal can cause serious complications, including cardiac tamponade, hemothorax, and hemorrhagic shock. Knowledge and experience on how to properly manage the stuck catheter are still limited. Case Presentation: Here, we present two cases that highlight the successful removal of the stuck tunneled CVC via thoracotomy through the close collaboration of multidisciplinary specialists in the best possible way. Both patients underwent an unsuccessful attempt at thrombolytic therapy with urokinase, catheter traction under the guidance of digital subtraction angiography and intraluminal balloon dilation. And we reviewed the literature on stuck catheters in the hope of providing knowledge and effective approaches to attempted removal of stuck catheters. Conclusion: There is no standardized procedure for dealing with stuck catheters. Intraluminal percutaneous transluminal angioplasty should be considered as the first-line treatment, while open surgery represents a second option only in the event of failure. Care must be taken that forced extubation can cause patients life-threatening.

Regeneration of Volumetric Muscle Loss Using MSCs Encapsulated in PRP-Derived Fibrin Microbeads.

Volumetric muscle loss (VML) is one of the major types of soft tissue injury frequently encountered worldwide. In case of VML, the endogenous regenerative capacity of the skeletal muscle tissue is usually not sufficient for complete healing of the damaged area resulting in permanent functional musculoskeletal impairment. Therefore, the development of new tissue engineering approaches that will enable functional skeletal muscle regeneration by overcoming the limitations of current clinical treatments for VML injuries has become a critical goal. Platelet-rich plasma (PRP) is an inexpensive and relatively effective blood product with a high concentration of platelets containing various growth factors and cytokines involved in wound healing and tissue regeneration. Due to its autologous nature, PRP has been a safe and widely used treatment option for various wound types for many years. Recently, PRP-based biomaterials have emerged as a promising approach to promote muscle tissue regeneration upon injury. This chapter describes the use of PRP-derived fibrin microbeads as a versatile encapsulation matrix for the localized delivery of mesenchymal stem cells and growth factors to treat VML using tissue engineering strategies.

Polymorphic lymphoproliferative disorder arising in a rheumatoid arthritis patient, presenting as fibrin-associated large B-cell lymphoma-like lesions in aortic and mitral valves.

We herein report a case of methotrexate-associated lymphoproliferative disorder (MTX-LPD) showing fibrin-associated large B-cell lymphoma-like heart valve lesions, and Epstein-Barr virus (EBV)-positive mucocutaneous ulcer-like cutaneous and oral mucosal lesions. MTX-LPD is a critical complication that can occur in RA patients who are treated with MTX. EBV also plays a defining or important role in LPDs. Among the sites of MTX-LPD, 40-50% occur in extranodal sites, including the gastrointestinal tract, skin, liver, lung, and kidney. There are few reports of MTX-LPDs involving the heart valves, and to the best of our knowledge, this is the first case to be reported in the English literature. The possibility of EBV-positive LPD should be considered in RA patients, even in patients with an atypical site, as in this case.

The Factors Associated With Decreasing Hemoglobin Levels and Platelet Counts After Trauma.

Objective In this study, we investigated the factors related to anemia and platelet reduction in patients with moderate to severe trauma to gain a deeper understanding of these phenomena. Methods Our study spanned the period from April 2021 to September 2023, and it involved a retrospective review of the hospital medical charts of all emergency outpatients of all ages who were transported by a physician-staffed helicopter and treated at our hospital and were diagnosed with an Injury Severity Score (ISS) of >8 by CT on arrival. The following data were analyzed: sex; age; mechanism of injury; vital signs upon arrival at the hospital; ISS; hemoglobin level and platelet count on arrival and day two; fibrin degradation product (FDP) level, lactate dehydrogenase (LDH) level, and diameter of the inferior vena cava (IVC) on arrival; and infusion volume on day one. We then statistically calculated the independent risk factors for differences between hemoglobin levels and platelet counts on arrival and those on day two. Results The study included a total of 209 subjects, with an average age of 58 years and a male predominance. Multivariate analysis showed that the FDP level, IVC diameter, and age were significantly associated with changes in hemoglobin levels on arrival and day two, whereas the IVC diameter, LDH, age, systolic blood pressure, and sex were significantly associated with changes in the platelet count on arrival and day two. Conclusions A noteworthy correlation was found between certain factors and changes in hemoglobin levels and platelet counts between the initial assessment and the second day in our cohort. We recommend further prospective research to determine whether our findings hold true for a larger population of trauma patients.

A role of methionines in the functioning of oxidatively modified fibrinogen.

Posttranslational modifications in fibrinogen resulting from induced oxidation or oxidative stress in the organism can have deleterious influence on optimal functioning of fibrinogen, causing a disturbance in assembly and properties of fibrin. The protective mechanism supporting the ability of fibrinogen to function in ROS-generating environment remains completely unexplored. The effects of very low and moderately low HOCl/-OCl concentrations on fibrinogen oxidative modifications, the fibrin network structure as well as the kinetics of both fibrinogen-to-fibrin conversion and fibrin hydrolysis have been explored in the current study. As opposed to 25 Μm, HOCl/-OCl, 10 µM HOCl/-OCl did not affect the functional activity of fibrinogen. It is shown for the first time that a number of Met residues, AαMet476, AαMet517, AαMet584, BßMet367, γMet264, and γMet94, identified in 10 µM HOCl/-OCl fibrinogen by the HPLC-MS/MS method, operate as ROS scavengers, performing an important antioxidant function. In turn, this indicates that the fibrinogen structure is adapted to the detrimental action of ROS. The results obtained in our study provide evidence for a protective mechanism responsible for maintaining the structure and functioning of fibrinogen molecules in the bloodstream under conditions of mild and moderate oxidative stress.

Surgical Management of Radicular Cyst with the Application of a Natural Platelet Concentrate and Ostoden: A Case Report.

The most frequent cystic lesions that affect the jaw are radicular cysts. The current case report describes the surgical management of a radicular cyst in the periapical region of maxillary central and lateral incisors, and highlights the efficacy of natural platelet concentrate [platelet-rich fibrin (PRF)] along with Ostoden bone graft material used for postoperative healing. A 46-year-old male patient presented to the department with swelling in the palatal aspect of the maxillary anterior region. On radiographic examination, a radiolucent periapical lesion was evident in relation to the left maxillary central and lateral incisor. In the maxillary anterior region, root canal therapy was performed, followed by periapical surgery, and PRF with Ostoden bone graft was placed in the surgical site to initiate the healing at a faster rate. The patient was recalled at follow-ups after 7 days, 3, 6, and 9 months. No symptoms such as pain, inflammation, or discomfort were observed during the review period.

A Comparative Evaluation of Efficacy of Root Surface Biomodification using MTAD, MTAD+I-PRF on Adhesion of Fibrin Clot to Dentin Sem Study.

Root biomodifiers help in removing the smear layer following mechanical debridement. In this context, we evaluated and compared the in vitro efficacy of MTAD, MTAD+I-PRF, and phosphate-buffered saline-conditioned dentin surfaces by examining the distribution of the fibrin network using scanning electron microscopy. It was concluded that MTAD can serve as a potentially useful root conditioner/biomodifier. Further, the adjunct of MTAD+I-P resulted in more fibrin network linkage on the dentinal surface when compared to MTAD alone which can be of great utility in Advanced Regenerative Therapy.

Clinical Evaluation of Coronally Advanced Flap with or without a Platelet-Rich Fibrin Membrane for the Root Coverage.

Aim: To evaluate "coronally advanced flap" with or without "a platelet-rich fibrin membrane for the root coverage." Materials and Methods: All the clinical parameters were assessed at different time intervals (at baseline, 1, 3, and 6 months) in both experimental and control group. Following "clinical parameters" were recorded using "UNC-15" "Probe-Plaque Index (PI)" (Silness and Loe, 1964), "Gingival Index" (GI) (Loe and Silness, 1963), "Recession depth (RD)," "Recession width (RW)," "Clinical attachment level (CAL)," and "Width of keratinized gingiva (WKG)". Results: At final evaluation (i.e., mean change from baseline to 6 months), "the decrease in Plaque Index was 2.5% higher in Group B (66.0%) as compared to Group A (63.5%). The decrease in Gingival Index was 6.1% higher in Group B (91.4%) as compared to Group A (85.3%), and the decrease in recession width was 4.0% higher in Group B (75.2%) as compared to Group A (71.2%). The decrease in clinical attachment level was 4.4% higher in Group B (53.2%) as compared to Group A (48.4%). The increase in width of keratinized gingiva was 1.9% higher in Group A (28.8%) as compared to Group B (26.9%)." Conclusion: The controlled, randomized, split mouth design showed that CAF surgery, either by alone or in combination with PRF, is an efficient treatment method for covering denuded roots. "This design was used to treat bilateral isolated Miller's class I and II recessions in gingival part. When compared to the CAF approach, the results from a combination of CAF and PRF after a 6-month period showed additional advantages in addition to mean root coverage in the treatment of Miller's classes I and II recessions in gingival part."

Towards optimized tissue regeneration: a new 3D printable bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate.

Introduction: Autologous platelet concentrate (APC) are pro-angiogenic and can promote wound healing and tissue repair, also in combination with other biomaterials. However, challenging defect situations remain demanding. 3D bioprinting of an APC based bioink encapsulated in a hydrogel could overcome this limitation with enhanced physio-mechanical interface, growth factor retention/secretion and defect-personalized shape to ultimately enhance regeneration. Methods: This study used extrusion-based bioprinting to create a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate. Chemico-physical testing exhibited an amorphous structure characterized by high shape fidelity. Cytotoxicity assay and incubation of human osteogenic sarcoma cells (SaOs2) exposed excellent biocompatibility. enzyme-linked immunosorbent assay analysis confirmed pro-angiogenic growth factor release of the printed constructs, and co-incubation with HUVECS displayed proper cell viability and proliferation. Chorioallantoic membrane (CAM) assay explored the pro-angiogenic potential of the prints in vivo. Detailed proteome and secretome analysis revealed a substantial amount and homologous presence of pro-angiogenic proteins in the 3D construct. Results: This study demonstrated a 3D bioprinting approach to fabricate a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate with high shape fidelity, biocompatibility, and substantial pro-angiogenic properties. Conclusion: This approach may be suitable for challenging physiological and anatomical defect situations when translated into clinical use.

Use of platelet- and leukocyte-rich fibrin (L-PRF) as a healing agent in the postoperative period of third molar removal surgeries: a systematic review.

OBJECTIVE: The aim of this study was to analyze the effectiveness of L-PRF as a healing agent in the postoperative period of third molar extraction surgeries, as well as to investigate secondary effects, such as the reduction of pain, edema and other discomforts after the surgical intervention. MATERIALS AND METHODS: The methodology adopted consisted of carrying out a systematic review of the literature, following the model outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The inclusion criteria were previously established according to a systematic review protocol approved by the Prospective Register of Systematic Reviews (PROSPERO) under number CRD42023484679. In order to carry out a comprehensive search, a search in five databases was carried out, PubMed, Web of Science, Scopus, Cochrane Library and Embase. RESULTS: The search resulted in the selection of randomized controlled trials that conformed to the established criteria. Two authors independently screened the records and extracted the data. The assessment of bias was conducted according to the guidelines recommended by the Cochrane Collaboration, using version 2 of the Cochrane tool for assessing the risk of bias in randomized trials (RoB 2). CONCLUSION: This study demonstrated that L-PRF stands out by providing direct benefits to healing, vascularization and tissue regeneration. CLINICAL RELEVANCE: L-PRF plays an important role in reducing postoperative pain, edema, the incidence of alveolar osteitis and infections after third molar removal surgery, compared to patients who did not undergo the use of L-PRF.

Improving the mechanical and biological functions of cell sheet constructs: The interplay of human-derived periodontal ligament stem cells, endothelial cells and plasma rich in growth factors.

OBJECTIVE: The aim of this study was to produce and characterize triple-layered cell sheet constructs with varying cell compositions combined or not with the fibrin membrane scaffold obtained by the technology of Plasma Rich in Growth Factors (mPRGF). MATERIALS AND METHODS: Human primary cultures of periodontal ligament stem cells (hPDLSCs) were isolated, and their stemness nature was evaluated. Three types of triple-layered composite constructs were generated, composed solely of hPDLSCs or combined with human umbilical vein endothelial cells (HUVECs), either as a sandwiched endothelial layer or as coculture sheets of both cell phenotypes. These three triple-layered constructs were also manufactured using mPRGF as cell sheets' support. Necrosis, glucose consumption, secretion of extracellular matrix proteins and synthesis of proangiogenic factors were determined. Histological evaluations and proteomic analyses were also performed. RESULTS: The inclusion of HUVECs did not clearly improve the properties of the multilayered constructs and yet hindered their optimal conformation. The presence of mPRGF prevented the shrinkage of cell sheets, stimulated the metabolic activity and increased the matrix synthesis. At the proteome level, mPRGF conferred a dramatic advantage to the hPDLSC constructs in their ability to provide a suitable environment for tissue regeneration by inducing the expression of proteins necessary for bone morphogenesis and cellular proliferation. CONCLUSIONS: hPDLSCs' triple-layer construct onto mPRGF emerges as the optimal structure for its use in regenerative therapeutics. CLINICAL RELEVANCE: These results suggest the suitability of mPRGF as a promising tool to support cell sheet formation by improving their handling and biological functions.

Platelet-rich fibrin: A review of its role as a new treatment in androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a major cause of hair loss resulting from a complex interplay between various genes and hormones with the result being follicular miniaturization and altered hair cycle dynamics. Platelet-rich plasma (PRP) has a well-established role as adjunctive therapy in AGA but there are many limitations of it. In an attempt to overcome the shortcomings of PRP, liquid platelet-rich fibrin (PRF) was developed. AIM: This article critically reviews the protocol for the preparation and clinical outcomes of PRF. PATIENTS/METHODS: The articles published so far in the English language regarding the preparation and clinical outcomes of PRF were reviewed. RESULTS: Among five studies analyzing various centrifugation speeds and centrifugation times, three of the studies favored low-speed centrifugation, whereas two studies did not support this methodology. A horizontal centrifuge may be preferred over a fixed-angle centrifuge for PRF. Five clinical studies on the use of PRF showed a significant effect on AGA. CONCLUSION: At present, there is no consensus regarding the preparation of PRF. Most studies used fixed-angle centrifugation favored low centrifuge speed and less centrifugation time. Larger studies are needed to determine the optimal centrifugation force and time. A horizontal centrifuge may be preferred over a fixed-angle centrifuge due to the higher yield of platelets, and lesser shear trauma to the cells. In addition, larger, well-designed studies are needed to confirm the benefits of PRF over PRP.

Horizontal ridge augmentation using guided bone regeneration with an association of particulate allografts mixed with platelet-rich fibrin, collagen membrane and tent-screws: A prospective study.

BACKGROUND: Guided Bone Regeneration (GBR) is a versatile technique employed not only to correct pre-implant alveolar bone defects but also to facilitate bone defect correction during simultaneous implant placement. The effectiveness of GBR varies significantly among different protocols, as reported in the literature. This study specifically aimed to radiologically evaluate the horizontal bone gain obtained using a GBR procedure combining a particulate allograft, platelet-rich fibrin, resorbable collagen membrane, and screw tents. MATERIALS AND METHODS: A total of 42 patients with an insufficient alveolar bone width for dental implant placement were treated with a GBR technique using a mixture of particulate allograft (demineralised freeze-dried bone allograft 300-500 and 500-1000 µm), advanced platelet-rich fibrin (A-PRF), resorbable collagen membranes and screws tents (1.2 mm in diameter). Over the course of the study, a total of 63 GBR procedures were performed on these patients. Bone gains were measured by cone-beam computed tomography at 9.1 ± 2.0 months post-operative. RESULTS: A significant mean increase (P < 0.001) of 3.2 ± 0.9 mm at the sites of the greatest bone defect was observed. This improvement was consistent across various locations, including both maxillary and mandibular regions, and in cases of terminal and embedded edentulism, without any post-operative complications during the entire post-operative follow-up. All patients benefited from implant placement following the bone augmentation protocol. CONCLUSION: GBR combining particulate allografts, A-PRF, collagen membranes, and screw tents achieves reliable, predictable, and reproducible clinical gains that allow for future implant placement.

In vitro effect of hydroxyethyl starch on COVID-19 patients-associated hypofibrinolytic state.

Background: Despite systematic thromboprophylaxis, 30% of the COVID-19 patients in intensive care units develop thrombosis. This occurrence is associated with a hypofibrinolytic state measured by thromboelastometry when adding tissue plasminogen activator (tPA) to citrated whole blood for a further run for EXTEM (ROTEM). Objectives: Because hydroxyethyl starches (HESs) affect fibrin polymerization, we have assessed its potential effect on in vitro tPA-induced fibrinolysis. Methods: Fifteen successive COVID-19 patients from the local intensive care units were selected for tPA resistance occurrence. HES was added to whole blood samples with proportion similar to the pharmacologic recommendations. Samples were run for EXTEM on a ROTEM delta device after further addition of tPA. Paired controls were whole blood samples with the same volume of saline added. To assess the impact of HES on coagulation, thrombin generation was measured in 10 COVID-19 patients in the presence of either HES or saline; then, the clots obtained were used to generate electron microscope images. Results: Clot firmness at 5 minutes and the lysis index at 30 minutes were decreased in presence of HES compared with saline (Wilcoxon test, P < .01 for HES vs saline and HES vs untreated). However, no statistically significant difference was observed for all thrombin generation assay parameters studied (endogenous thrombin potential, peak thrombin, and time to peak). With HES, fibrin fibers of either COVID-19 patients or control subjects were thicker than those of saline-treated samples. Conclusion: These results highlight that HES increased apparent in vitro tPA-induced fibrinolysis in case of severe COVID-19 disease. Use of this plasma volume expander may translate as a potential help against COVID-19-induced thrombosis occurrence.

Endoscopic treatment of anastomotic leakage after colorectal surgery by using polyglycolic acid sheets and fibrin glue.

We describe the case of a 66-year-old man with an anastomotic fistula after rectal surgery, which was treated colonoscopically using polyglycolic acid sheets and fibrin glue. Polyglycolic acid sheets and fibrin glue have been used in thoracic surgery and otolaryngology to reinforce sutures and prevent air leakage. There have been recent reports of their use in endoscopic surgery for the closure of intraoperative perforations after endoscopic submucosal dissection and for fistula closure after upper gastrointestinal tract surgery. However, anastomotic fistulas in colorectal surgery are difficult to visualize endoscopically and may be difficult to suture with clips due to fibrosis. Polyglycolic acid sheets can be easily trimmed, and the fistula can be easily filled using these sheets; moreover, using fibrin glue to fix the sheets may enable fistula closure in areas that are difficult to visualize endoscopically.

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.