Resident macrophage-dependent immune cell scaffolds drive anti-bacterial defense in the peritoneal cavity.

Peritoneal immune cells reside unanchored within the peritoneal fluid in homeostasis. Here, we examined the mechanisms that control bacterial infection in the peritoneum using a mouse model of abdominal sepsis following intraperitoneal Escherichia coli infection. Whole-mount immunofluorescence and confocal microscopy of the peritoneal wall and omentum revealed that large peritoneal macrophages (LPMs) rapidly cleared bacteria and adhered to the mesothelium, forming multilayered cellular aggregates composed by sequentially recruited LPMs, B1 cells, neutrophils, and monocyte-derived cells (moCs). The formation of resident macrophage aggregates (resMφ-aggregates) required LPMs and thrombin-dependent fibrin polymerization. E. coli infection triggered LPM pyroptosis and release of inflammatory mediators. Resolution of these potentially inflammatory aggregates required LPM-mediated recruitment of moCs, which were essential for fibrinolysis-mediated resMφ-aggregate disaggregation and the prevention of peritoneal overt inflammation. Thus, resMφ-aggregates provide a physical scaffold that enables the efficient control of peritoneal infection, with implications for antimicrobial immunity in other body cavities, such as the pleural cavity or brain ventricles.

Clot or Not? Reviewing the Reciprocal Regulation Between Lipids and Blood Clotting.

Both hyperlipidemia and thrombosis contribute to the risks of atherosclerotic cardiovascular diseases, which are the leading cause of death and reduced quality of life in survivors worldwide. The accumulation of lipid-rich plaques on arterial walls eventually leads to the rupture or erosion of vulnerable lesions, triggering excessive blood clotting and leading to adverse thrombotic events. Lipoproteins are highly dynamic particles that circulate in blood, carry insoluble lipids, and are associated with proteins, many of which are involved in blood clotting. A growing body of evidence suggests a reciprocal regulatory relationship between blood clotting and lipid metabolism. In this review article, we summarize the observations that lipoproteins and lipids impact the hemostatic system, and the clotting-related proteins influence lipid metabolism. We also highlight the gaps that need to be filled in this area of research.

Ascites microenvironment conditions the peritoneal pre-metastatic niche to promote the implantation of ovarian tumor spheroids: Involvement of fibrinogen/fibrin and αV and α5ß1 integrins.

At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence especially because of the propensity of the OC cells to spread in the abdominal cavity leading to peritoneal metastasis. The influence of ascites on the development of pre-metastatic niches, and on the biological mechanisms leading to cancer cell colonization of the mesothelium, remains poorly understood. Here, we show that ascites weakens the mesothelium by affecting the morphology of mesothelial cells and by destabilizing their distribution in the cell cycle. Ascites also causes destabilization of the integrity of mesothelium by modifying the organization of cell junctions, but it does not affect the synthesis of N-cadherin and ZO-1 by mesothelial cells. Moreover, ascites induces disorganization of focal contacts and causes actin cytoskeletal reorganization potentially dependent on the activity of Rac1. Ascites allows the densification and reorganization of ECM proteins of the mesothelium, especially fibrinogen/fibrin, and indicates that it is a source of the fibrinogen and fibrin surrounding OC spheroids. The fibrin in ascites leads to the adhesion of OC spheroids to the mesothelium, and ascites promotes their disaggregation followed by the clearance of mesothelial cells. Both αV and α5ß1 integrins are involved. In conclusion ascites and its fibrinogen/fibrin composition affects the integrity of the mesothelium and promotes the integrin-dependent implantation of OC spheroids in the mesothelium.

Structural control of fibrin bioactivity by mechanical deformation.

Fibrin is the fibrous protein network that comprises blood clots; it is uniquely capable of bearing very large tensile strains (up to 200%) due to multiscale force accommodation mechanisms. Fibrin is also a biochemical scaffold for numerous enzymes and blood factors. The biomechanics and biochemistry of fibrin have been independently studied. However, comparatively little is known about how fibrin biomechanics and biochemistry are coupled: how does fibrin deformation influence its biochemistry? In this study, we show that mechanically induced protein structural changes in fibrin affect fibrin biochemistry. We find that tensile deformation of fibrin leads to molecular structural transitions of α-helices to ß-sheets, which reduced binding of tissue plasminogen activator (tPA), an enzyme that initiates fibrin lysis. Moreover, binding of tPA and Thioflavin T, a commonly used ß-sheet marker, were mutually exclusive, further demonstrating the mechano-chemical control of fibrin biochemistry. Finally, we demonstrate that structural changes in fibrin suppressed the biological activity of platelets on mechanically strained fibrin due to reduced αIIbß3 integrin binding. Our work shows that mechanical strain regulates fibrin molecular structure and biological activity in an elegant mechano-chemical feedback loop, which possibly extends to other fibrous biopolymers.

Dynamic Imaging of Blood Coagulation Within the Hematoma of Patients With Acute Hemorrhagic Stroke.

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making. METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, which can be measured noninvasively using quantitative susceptibility mapping and diffusion tensor imaging. In this serial magnetic resonance imaging study, we enrolled 24 patients with acute intracerebral hemorrhage between October 2021 to May 2022 at a stroke center. Patients were 30 to 70 years of age and had a hematoma volume >15 cm3 and National Institutes of Health Stroke Scale score >1. The patients underwent imaging 3×: within 12 to 24 (T1), 36 to 48 (T2), and 60 to 72 (T3) hours of last seen well on a 3T magnetic resonance imaging system. Three-dimensional anatomic, multigradient echo and 2-dimensional diffusion tensor images were obtained. Hematoma and edema volumes were calculated, and the distribution of coagulation was measured by dynamic changes in the susceptibilities and fractional anisotropy within the hematoma. RESULTS: Using a coagulated blood phantom, we demonstrated a linear relationship between the percentage coagulation and susceptibility (R2=0.91) with a positive red blood cell stain of the clot. The quantitative susceptibility maps showed a significant increase in hematoma susceptibility (T1, 0.29±0.04 parts per millions; T2, 0.36±0.04 parts per millions; T3, 0.45±0.04 parts per millions; P<0.0001). A concomitant increase in fractional anisotropy was also observed with time (T1, 0.40±0.02; T2, 0.45±0.02; T3, 0.47±0.02; P<0.05). CONCLUSIONS: This quantitative neuroimaging study of coagulation within the hematoma has the potential to improve patient management, such as safe resumption of anticoagulants, the need for reversal agents, the administration of alteplase to resolve the clot, and the need for surgery.

Evaluation of the effect of injectable platelet-rich fibrin (i-PRF) in wound healing and growth factor release in rats: a split-mouth study.

This experimental study aimed to evaluate the effects of injectable platelet-rich fibrin (i-PRF) on mucosal healing and the release of growth factors in rats. 40 rats were used; i-PRF was administered in the right buccal area while saline was injected in the left. Cytokeratin, FGF, PDGF, TGF, and VEGF expressions were determined with immunohistochemistry. Gene expressions of EGF, TGF-ß, and VEGF were analysed. Epithelialization started on the 3rd day, and connective tissue maturation was more prominent in the i-PRF-applied group. Also, the releases of VEGF, EGF, TGF-ß, PDGF, and FGF were higher in the i-PRF group during the 14 days. Gene expression analysis showed that changes in TGF-ß at 14 days after i-PRF injection and VEGF after 21 days were statistically significant. The results of this study suggested that autologous i-PRF application enhanced the healing of oral mucosal wounds by increasing the release of growth factors for 21 days.

Fibrin Hydrogels Reinforced by Reactive Microgels for Stimulus-Triggered Drug Administration.

Tissue engineering is a steadily growing field of research due to its wide-ranging applicability in the field of regenerative medicine. Application-dependent mechanical properties of a scaffold material as well as its biocompatibility and tailored functionality represent particular challenges. Here the properties of fibrin-based hydrogels reinforced by functional cytocompatible poly(N-vinylcaprolactam)-based (PVCL) microgels are studied and evaluated. The employment of temperature-responsive microgels decorated by epoxy groups for covalent binding to the fibrin is studied as a function of cross-linking degree within the microgels, microgel concentration, as well as temperature. Rheology reveals a strong correlation between the mechanical properties of the reinforced fibrin-based hydrogels and the microgel rigidity and concentration. The incorporated microgels serve as cross-links, which enable temperature-responsive behavior of the hydrogels, and slow down the hydrogel degradation. Microgels can be additionally used as carriers for active drugs, as demonstrated for dexamethasone. The microgels' temperature-responsiveness allows for triggered release of payload, which is monitored using a bioassay. The cytocompatibility of the microgel-reinforced fibrin-based hydrogels is demonstrated by LIVE/DEAD staining experiments using human mesenchymal stem cells. The microgel-reinforced hydrogels are a promising material for tissue engineering, owing to their superior mechanical performance and stability, possibility of drug release, and retained biocompatibility.

Elevated factor XI is associated with recurrent left ventricular thrombus of unknown origin.

BACKGROUND: Elevated factor XI (FXI) has been shown to predispose to thromboembolism. We investigated whether it is associated with left ventricular thrombus (LVT) formation, its recurrence and subsequent thromboembolic events. METHODS: In 54 patients with prior LVT of unknown origin, who stopped anticoagulation and 54 controls, we determined FXI, along with plasma clot permeability (Ks), fibrinolysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (vWF) and fibrinolysis proteins. During follow-up, the primary endpoint involving the recurrence of LVT a symptomatic ischemic stroke or systemic embolism was recorded. RESULTS: Elevated (>120%) FXI levels were more often observed in LVT patients when compared to the control group (14 [25.9%] vs. 6 [11.1%], p = .048) in association with the presence of active FXI. FXI correlated with age (r = .406, p = .002), Ks (r = -.542, p < .001) and CLT (r = .406, p = .002), also after adjustment for age, but not with ETP, vWF or fibrinolysis proteins. During follow-up of 77.6 ± 18.5 months the primary endpoint occurred in 17 (31.5%) LVT patients, including 11 (20.4%) recurrent LVT, and in 4 (7.4%) controls (annual incidence rate 4.9% vs. 1.1%, respectively; p = .002). On multivariate logistic regression analysis, elevated FXI was independently associated with the primary endpoint (OR 1.18; 95% CI 1.09-1.28). CONCLUSIONS: Elevated FXI in association with a prothrombotic state characterizes patients with prior LVT of unknown origin and predisposes to its recurrence and/or ischemic stroke during follow-up. It might be speculated that the measurement of FXI helps identify patients who could benefit from prolonged anticoagulation and FXI inhibitors in the future.

Bioprinted dermis with human adipose tissue-derived microvascular fragments promotes wound healing.

Tissue-engineered skin is an effective material for treating large skin defects in a clinical setting. However, its use is limited owing to vascular complications. Human adipose tissue-derived microvascular fragments (HaMVFs) are vascularized units that form vascular networks by rapid reassembly. In this study, we designed a vascularized bionic skin tissue using a three-dimensional (3D) bioprinter of HaMVFs and human fibroblasts encapsulated in a hybrid hydrogel composed of GelMA, HAMA, and fibrinogen. Tissues incorporating HaMVFs showed good in vitro vascularization and mechanical properties after UV crosslinking and thrombin exposure. Thus, the tissue could be sutured appropriately to the wound. In vivo, the vascularized 3D bioprinted skin promoted epidermal regeneration, collagen maturation in the dermal tissue, and vascularization of the skin tissue to accelerate wound healing. Overall, vascularized 3D bioprinted skin with HaMVFs is an effective material for treating skin defects and may be clinically applicable to reduce the necrosis rate of skin grafts.

Improving stability of human three dimensional skin equivalents using plasma surface treatment.

In developing three-dimensional (3D) human skin equivalents (HSEs), preventing dermis and epidermis layer distortion due to the contraction of hydrogels by fibroblasts is a challenging issue. Previously, a fabrication method of HSEs was tested using a modified solid scaffold or a hydrogel matrix in combination with the natural polymer coated onto the tissue culture surface, but the obtained HSEs exhibited skin layer contraction and loss of the skin integrity and barrier functions. In this study, we investigated the method of HSE fabrication that enhances the stability of the skin model by using surface plasma treatment. The results showed that plasma treatment of the tissue culture surface prevented dermal layer shrinkage of HSEs, in contrast to the HSE fabrication using fibronectin coating. The HSEs from plasma-treated surface showed significantly higher transepithelial electrical resistance compared to the fibronectin-coated model. They also expressed markers of epidermal differentiation (keratin 10, keratin 14 and loricrin), epidermal tight junctions (claudin 1 and zonula occludens-1), and extracellular matrix proteins (collagen IV), and exhibited morphological characteristics of the primary human skins. Taken together, the use of plasma surface treatment significantly improves the stability of 3D HSEs with well-defined dermis and epidermis layers and enhanced skin integrity and the barrier functions.

IL-1ß Impacts Vascular Integrity and Lymphatic Function in the Embryonic Omentum.

BACKGROUND: The chromatin-remodeling enzyme BRG1 (brahma-related gene 1) regulates gene expression in a variety of rapidly differentiating cells during embryonic development. However, the critical genes that BRG1 regulates during lymphatic vascular development are unknown. METHODS: We used genetic and imaging techniques to define the role of BRG1 in murine embryonic lymphatic development, although this approach inadvertently expanded our study to multiple interacting cell types. RESULTS: We found that omental macrophages fine-tune an unexpected developmental process by which erythrocytes escaping from naturally discontinuous omental blood vessels are collected by nearby lymphatic vessels. Our data indicate that circulating fibrin(ogen) leaking from gaps in omental blood vessels can trigger inflammasome-mediated IL-1ß (interleukin-1ß) production and secretion from nearby macrophages. IL-1ß destabilizes adherens junctions in omental blood and lymphatic vessels, contributing to both extravasation of erythrocytes and their uptake by lymphatics. BRG1 regulates IL-1ß production in omental macrophages by transcriptionally suppressing the inflammasome trigger RIPK3 (receptor interacting protein kinase 3). CONCLUSIONS: Genetic deletion of Brg1 in embryonic macrophages leads to excessive IL-1ß production, erythrocyte leakage from blood vessels, and blood-filled lymphatics in the developing omentum. Altogether, these results highlight a novel context for epigenetically regulated crosstalk between macrophages, blood vessels, and lymphatics.

The emerging role of fibrin(ogen) in cardiovascular disease.

OBJECTIVE: A coagulation factor called fibrinogen is produced by the liver and is proteolyzed by thrombin to become fibrin. The latest studies have revealed that fibrin(ogen) palys an essential role in the regulation of cardiovascular disease. Understanding the relationship and mechanism between fibrin(ogen) and cardiovascular disease is of great significance for maintaining overall health. The objective of this review is to discuss the specific involvement and underlying mechanisms of fibrin(ogen) in cardiovascular disease. METHODS: A review was conducted using the PubMed database to identify and analyze the emerging role of fibrinogen in cardiovascular disease. RESULTS: The literature review revealed that fibrin(ogen) plays a pivotal role in maintaining cardiovascular disease and are involved in the pathogenesis of cardiovascular disease. Fibrin(ogen) mainly influence various pathophysiological processes, such as participating in thrombosis formation, stimulating the inflammatory response, and other molecular pathways. CONCLUSION: This review focuses on the involvement of fibrin(ogen) in cardiovascular disease, with a particular emphasis on the main functions and underlying mechanisms by which fibrin(ogen) influence the pathogenesis and progression of these conditions. This review underscores the potential of fibrin(ogen) as therapeutic targets in managing cardiovascular disease.

Contrast-Free Endovascular Aneurysm Repair Combined With Fibrin Sealant Filling for Treating Abdominal Aortic Aneurysm: Technical Note.

INTRODUCTION: Endovascular aneurysm repair using iodinated contrast agents risks contrast-induced nephropathy, especially in high-risk patients. This technical note describes a contrast-free endovascular aneurysm repair (EVAR) protocol using preoperative imaging measurement and fibrin sealant (FS) filling. TECHNIQUE: Preoperative imaging measurement and intraoperative guidewire manipulation facilitated anatomical identification without contrast. After endograft deployment, the aneurysm sac was filled with FS if endoleak was indicated by pressure fluctuations. RESULT: Between 2017 and 2020, 6 high-risk patients underwent contrast-free EVAR with FS filling. Complete exclusion was achieved in all cases. Over follow-up, no endoleaks, deterioration in renal function, or other complications were observed. CONCLUSION: Contrast-free EVAR with FS filling shows early feasibility as an alternative technique for contrast-induced nephropathy (CIN) high-risk patients, while larger studies with long-term monitoring are imperative to validate outcomes. CLINICAL IMPACT: This study showcases a contrast-free EVAR technique with fibrin sealant filling for high-risk CIN patients. It offers a safer approach for those with renal challenges, reducing CIN risk. The technique's feasibility in a small cohort suggests its utility in treating AAA without iodinated contrast, crucial for patients with specific health risks. For clinicians, it introduces a method that decreases nephrotoxic risks, potentially changing practice for vulnerable patients.

Research and Clinical Approaches to Assess Platelet Function in Flowing Blood.

Platelet adhesion and activation is fundamental to the formation of a hemostatic response to limit loss of blood and instigate wound repair to seal a site of vascular injury. The process of platelet aggregate formation is supported by the coagulation system driving injury-proximal formation of thrombin, which converts fibrinogen to insoluble fibrin. This highly coordinated series of molecular and membranous events must be routinely achieved in flowing blood, at vascular fluid shear rates that place significant strain on molecular and cellular interactions. Platelets have long been recognized to be able to slow down and adhere to sites of vascular injury and then activate and recruit more platelets that forge and strengthen adhesive ties with the vascular wall under these conditions. It has been a major challenge for the Platelet Research Community to construct experimental conditions that allow precise definition of the molecular steps occurring under flow. This brief review will discuss work to date from our group, as well as others that has furthered our understanding of platelet function in flowing blood.

Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial.

BACKGROUND: Thrombo-inflammation is central to COVID-19-associated coagulopathy. TF (tissue factor), a driver of disordered coagulation and inflammation in viral infections, may be a therapeutic target in COVID-19. The safety and efficacy of the novel TF inhibitor rNAPc2 (recombinant nematode anticoagulation protein c2) in COVID-19 are unknown. METHODS: ASPEN-COVID-19 was an international, randomized, open-label, active comparator clinical trial with blinded end point adjudication. Hospitalized patients with COVID-19 and elevated D-dimer levels were randomized 1:1:2 to lower or higher dose rNAPc2 on days 1, 3, and 5 followed by heparin on day 8 or to heparin per local standard of care. In comparisons of the pooled rNAPc2 versus heparin groups, the primary safety end point was major or nonmajor clinically relevant International Society of Thrombosis and Haemostasis bleeding through day 8. The primary efficacy end point was proportional change in D-dimer concentration from baseline to day 8, or discharge if before day 8. Patients were followed for 30 days. RESULTS: Among 160 randomized patients, median age was 54 years, 43.1% were female, and 38.8% had severe baseline COVID-19. There were no significant differences between rNAPc2 and heparin in bleeding or other safety events. Overall, median change in D-dimer was -16.8% (interquartile range, -45.7 to 36.8; P=0.41) with rNAPc2 treatment and -11.2% (-36.0 to 34.4; P=0.91) with heparin (Pintergroup=0.47). In prespecified analyses, in severely ill patients, D-dimer levels tended to increase more within the heparin (median, 29.0% [-14.9 to 145.2]; P=0.02) than the rNAPc2 group (median, 25.9% [-49.1 to 136.4]; P=0.14; Pintergroup=0.96); in mildly ill patients, D-dimer levels were reduced within each group with a numerically greater reduction with rNAPc2 versus heparin (rNAPc2 median, -32.7% [-44.7 to 4.3]; P=0.007 and heparin median, -16.8% [-36.0 to 0.5]; P=0.008, Pintergroup=0.34). CONCLUSIONS: rNAPc2 treatment in hospitalized patients with COVID-19 was well tolerated without excess bleeding or serious adverse events but did not significantly reduce D-dimer more than heparin at day 8. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04655586.

Histopathological Features of Cancer-Associated Venous Thromboembolism: Presence of Intrathrombus Cancer Cells and Prothrombotic Factors.

BACKGROUND: Cancer-associated venous thromboembolism (VTE) is a critical complication in patients with cancer. However, the pathological findings of VTE are limited. Here, we investigated the histopathological features of cancer-associated VTE in human autopsy cases. METHODS: We clinically examined the autopsy cases of VTE with (n=114) and without cancer (n=66) and immunohistochemically analyzed the expression of prothrombotic factors in intrathrombus cancer cells, the thrombus contents of erythrocytes, fibrin, platelets, citrullinated histone H3, and degree of organization. RESULTS: Vascular wall invasion or small cell clusters of cancer cells was observed in thrombi in 27.5% of deep vein thrombosis and 25.9% of pulmonary embolism cases. The majority of the cancer cells in deep vein thrombi appeared to be invading the vessel wall, whereas the majority of pulmonary thrombi had cancer cell clusters, consistent with embolization via blood flow. These cancer cells were immunohistochemically positive for TF (tissue factors) or podoplanin in up to 88% of VTE cases. The frequency of TF-positive monocyte/macrophages in thrombi was higher in cancer-associated VTE than that in VTE without cancer. Citrullinated histone H3 was predominantly observed in the early stages of organizing thrombi. There was no significant difference in thrombus components between VTE with cancer and without cancer groups. CONCLUSIONS: Vascular wall invasion or cancer cell clusters in thrombi might influence thrombogenesis of cancer-associated VTE. TF and podoplanin in cancer cells and in monocyte/macrophages may induce coagulation reactions and platelet aggregation. Neutrophil extracellular traps may play a role in the early stages of VTE, regardless of cancer status.

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.

How to explain the beneficial effects of leukocyte- and platelet-rich fibrin.

The survival of an organism relies on its ability to repair the damage caused by trauma, toxic agents, and inflammation. This process involving cell proliferation and differentiation is driven by several growth factors and is critically dependent on the organization of the extracellular matrix. Since autologous platelet concentrates (APCs) are fibrin matrices in which cells, growth factors, and cytokines are trapped and delivered over time, they are able to influence that response at different levels. The present review thoroughly describes the molecular components present in one of these APCs, leukocyte- and platelet-rich fibrin (L-PRF), and summarizes the level of evidence regarding the influence of L-PRF on anti-inflammatory reactions, analgesia, hemostasis, antimicrobial capacity, and its biological mechanisms on bone/soft tissue regeneration.

Endodontic surgery and platelet concentrates: A comprehensive review.

While autologous platelet concentrates (APCs) have gained traction as promising regenerative materials in recent years, their impact on wound healing and tissue regeneration in periapical hard tissue defects remains controversial. Endodontic microsurgery (EMS) has embraced the potential of platelet concentrates, particularly L-PRF (Leucocyte-Platelet-Rich Fibrin) and PRP (Platelet-Rich Plasma), as regenerative tools. These concentrates, rich in growth factors and other bioactive molecules, are thought to enhance healing and treatment outcomes for various endodontic conditions. However, their effectiveness remains a subject of investigation. Despite encouraging 3-D cone beam computed tomography (CBCT) based evidence for PRP's effectiveness in complex lesions and apico-marginal defects, inconsistencies in its performance across preparation and application protocols raise questions about its superiority over existing options. More research is crucial to understand its full potential as a reliable regenerative tool in endodontics. L-PRF and its derivatives are particularly effective in treating apical-marginal defects. It enhances clinical attachment levels and reduces probing pocket depths, likely due to its slow and coordinated release of various growth factors. L-PRF has been shown to also improve patients' quality of life by reducing postoperative swelling and pain. However, more research is needed to standardize its preparation methods and confirm its long-term benefits. This paper aims to provide a comprehensive review of the current knowledge and recent advances in endodontic surgery and the use of platelet concentrates, focusing on their roles in managing periapical lesions and endo-perio lesions.

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.