Search Results (175)

Background/Objectives: Chronic wounds remain a formidable clinical challenge due to the suboptimal efficacy of conventional delivery systems and therapeutics. Textilinin-1, a venom-derived Kunitz-type serine protease inhibitor, has previously established its profile as a potent hemostatic agent. However, its potential as a multifunctional biopharmaceutical for wound management remains largely untapped. This study evaluates the pharmacological effects of Textilinin-1 in preclinical models of cutaneous wound repair. Methods: We employed an integrated platform comprising bioinformatics, in vitro cellular assays, and in vivo murine excisional wounds and a pilot porcine proof-of-concept model to assess the wound healing-promoting effects of Textilinin-1 and explore associated cellular responses associated with key stages of the wound healing cascade. Results: Textilinin-1 was associated with multiple cellular responses relevant to tissue repair. It attenuated M1-like inflammatory activation and showed preliminary growth-inhibitory activity against Staphylococcus aureus under the tested conditions. Concurrently, it enhanced the proliferative and migratory capacity of fibroblasts, endothelial cells, and keratinocytes, which are key cellular targets for wound closure. In pre-clinical pilot porcine and rodent models, Textilinin-1 treatment was associated with accelerated wound contraction and improved structural tissue quality. Conclusions: Our findings provide preclinical evidence that Textilinin-1 may promote cutaneous wound repair and modulate cellular responses relevant to key stages of the wound healing cascade. These results support further investigation of Textilinin-1 as a candidate for wound repair applications. Future studies are required to define its precise molecular mechanisms, evaluate its efficacy in chronic or otherwise compromised wound models, and optimize its topical formulation or hydrogel-based delivery. Full article

The rapid hemostasis of deep and irregular wounds is of great clinical significance. In this study, an injectable hemostatic hydrogel based on bioorthogonal conjugation was developed. This gel uses thrombin (TMB) as the hemostatic active substance and 4ARM-PEG-N₃ as the crosslinking agent, which undergo orthogonal conjugation via the classic azide–alkyne click reaction to form an injectable hydrogel (TMB-PEG). The resulting hydrogel exhibited a transparent, injectable gel state. TEM images revealed that the hydrogel comprised sheet-like structures and interwoven fibers with a diameter of approximately 100 nanometers. In a puncture bleeding wound model, hemostasis with the TMB-PEG hydrogel required only 25 s, with a blood loss of 1.9 ± 1.3 mg, both approximately one-sixth of that of the control group. Moreover, the hemostatic performance of the TMB-PEG hydrogel was far superior to that of three other commonly used hemostatic materials. Furthermore, cephalosporin antibiotics were conjugated to the hemostatic gel via orthogonal reactions, endowing it with significant broad-spectrum antibacterial activity, achieving over 99% antibacterial efficacy against both Gram-negative and Gram-positive bacteria. Full article

Background and Objectives: With contemporary blood management strategies substantially reducing transfusion rates after total knee arthroplasty (TKA), conventional endpoints such as transfusion incidence and estimated blood loss may have limited sensitivity for evaluating adjunctive hemostatic interventions. As postoperative anemia evolves dynamically over time, hemoglobin kinetics and cumulative anemia burden may offer more informative measures of treatment effect. This study evaluated whether implementation of a topical thrombin–carboxymethyl starch hemostatic agent within a standardized modern blood management protocol was associated with smaller early postoperative hemoglobin decline and lower cumulative anemia burden after TKA. Materials and Methods: In this single-center, retrospective, pre–post observational study, consecutive patients aged 50 years or older undergoing primary unilateral TKA for osteoarthritis before and after implementation of a thrombin–carboxymethyl starch topical hemostatic agent were compared. Perioperative management was otherwise standardized and unchanged. Patients were matched 1:1 using propensity scores derived from eight prespecified covariates. Co-primary endpoints were hemoglobin change from baseline to postoperative day 1 and day 2, and cumulative anemia burden quantified by the area under the hemoglobin-deficit curve from POD 0 to POD 13 was assessed as a key secondary endpoint. Results: Of 564 patients assessed for eligibility, 328 met the inclusion criteria, and 70 propensity score-matched pairs were included in the final analysis. Unless otherwise specified, the outcomes reported below were analyzed in these 70 matched pairs. In the matched cohort, the intervention group had a lesser hemoglobin decrease at postoperative day (POD) 1 than the control group (2.12 ± 0.97 vs. 2.42 ± 0.98 g/dL), corresponding to a paired mean difference of 0.30 g/dL (95% CI, 0.08–0.52; p = 0.008). The between-group difference at POD 2 was not statistically significant (paired mean difference, 0.15 g/dL; 95% CI, −0.03 to 0.33; p = 0.10). The area under the hemoglobin-deficit curve from POD 0 to POD 13 was lower in the intervention group (18.6 ± 5.2 vs. 21.3 ± 5.6 g/dL × day), with a paired mean difference of 2.7 g/dL × day (95% CI, 0.9–4.5; p = 0.004). Estimated total blood loss, formula-derived hidden blood loss, and transfusion rates did not differ significantly between groups. Conclusions: Use of a thrombin–carboxymethyl starch topical hemostatic agent was associated with modest attenuation of early postoperative hemoglobin decline and lower cumulative anemia burden after TKA, without significant differences in estimated blood loss or transfusion occurrence. Hemoglobin kinetics and cumulative anemia burden may provide complementary outcome measures in contemporary low-transfusion practice, although these findings should be interpreted cautiously given the observational design and low transfusion event rate. Full article

Gelatin methacrylate (GelMA) hydrogels are promising carriers for bioactive agents like curcumin (Cur) and adenosine diphosphate (ADP) in wound healing. However, existing GelMA-based systems fail to achieve both rapid hemostasis and sustained anti-inflammatory effects. In this study, we developed a Cur/ADP GelMA hydrogel, and evaluated its anti-inflammatory, regenerative, hemostatic, and biocompatible properties. Proton nuclear magnetic resonance (¹H-NMR) analysis showed that a 65% degree of substitution of GelMA is optimal for wound dressings. Scanning electron microscopy revealed a uniform pore size, aiding inflammatory exudate removal. The Cur/ADP GelMA hydrogel exhibited strong adhesion, stability, and antibacterial activity, reducing E. coli and S. aureus proliferation by 85% and 72%, respectively. Hemostatic effects were observed, with blood loss reduced to 238 ± 23 mg compared to 559 ± 18 mg in the untreated group. The ELISA results showed reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and increased IL-10. In vivo studies demonstrated 98% wound closure by day 14, enhanced granulation tissue formation, and a 70% thicker epidermis compared to controls. Mechanistically, ADP accelerates platelet activation and clot formation, while Cur modulates the inflammatory microenvironment, enabling synergistic hemostasis and immune regulation, thus promoting accelerated wound healing. Full article

Viscoelastic testing (VET) is widely used to guide hemostatic therapy in patients with coagulopathy. One important application is the detection of fibrinolysis, defined as a reduction in clot amplitude after maximum clot firmness (MCF), quantified as maximum lysis (ML). Low ML values have recently been associated with adverse outcomes in trauma and sepsis. However, the biological basis of low ML remains unclear. Objective: To determine whether low ML values reflect reduced plasmin-mediated fibrinolysis in tissue factor (TF) activated viscoelastic assays (EX-assay). Methods: A total of 120 healthy adults (52.5% female; mean age 38.2 ± 14.1 years) were studied. EX-assay without fibrinolysis inhibition were compared with assays containing the antifibrinolytic agent tranexamic acid (AP-assay). VET parameters obtained with and without fibrinolysis inhibition were compared using paired analyses, Pearson correlation, and Bland–Altman methods. Results: Clot firmness at 10 min (CA10) was similar with or without fibrinolysis inhibition; although MCF differed statistically, the difference was clinically negligible. ML ranged from 1% to 13% in both assays, with nearly identical mean values (5.9 ± 2.6% vs. 6.0 ± 2.6%). Correlation analysis demonstrated strong agreement for CA10, MCF, and ML between assays, and Bland–Altman analysis confirmed minimal bias for ML. Conclusions: Low ML values in TF-triggered viscoelastic assays were unaffected by tranexamic acid, suggesting that they are unlikely to reflect plasmin-mediated fibrinolysis. These findings support the contribution of alternative mechanisms, such as platelet-mediated clot retraction. Full article

Achieving hemostasis is crucial in neurosurgery, yet conventional methods are not always feasible, making topical hemostatic agents necessary. Current resorbable hemostatic agents allow effective hemostasis but must remain in situ to prevent rebleeding. This can provoke foreign body reactions leading to prolonged microglia-mediated neuroinflammation, which may exacerbate damage and delay recovery. It highlights the need for new hemostatic materials that can be removed after controlling bleeding while being safe for neurons and microglia. One candidate is Hemo-Ionic, a non-resorbable hemostatic compress composed of calcium alginate and zinc (Zn²⁺). Hemo-Ionic previously demonstrated effective in vitro and in vivo hemostasis, comparable to Surgicel and TachoSil, and pro-repair properties. In this study, Hemo-Ionic’s effect on neuronal and microglial cells was investigated in vitro. Results showed that Hemo-Ionic preserved cell viability and had an antioxidant capacity through protection from lipid peroxidation. Hemo-Ionic also reduced nitric oxide and pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) expression and release by lipopolysaccharide (LPS)-stimulated microglial cells. Finally, neuronal viability was restored when exposed to supernatants of Hemo-Ionic-treated microglia. These findings indicate that Hemo-Ionic’s safety and capacity to reduce neuroinflammation, combined with its hemostatic efficacy and non-resorbable nature, make it a promising alternative to resorbable hemostatic agents used in neurosurgery. Full article

Two hemostatic bionanocomposite dressings were developed using natural, semi-natural (or semi-synthetic) and synthetic polymers. The first system consisted of chitosan (CS), polyvinyl alcohol (PVA), and carboxymethyl cellulose (CMC) (CS/PVA/CMC), while the second was based on CS, PVA, and starch (SR) (CS/PVA/SR). Zinc oxide (ZnO) nanoparticles and bicyclic monoterpene camphor (CP) ketone were incorporated as bioactive agents in order to enhance antimicrobial and hemostatic performance. FTIR spectroscopy confirmed the successful solvent casting synthesis of the dressings and the interactions between the biopolymers and additives. XRD analysis indicated a predominantly amorphous structure, while SEM images and EDS analysis revealed uniform dispersion of ZnO particles within the polymer matrices without aggregation. Furthermore, the CS/PVA/CMC-1ZnO/CP sample exhibited a water sorption of 12,666 ± 126%, while CS/PVA/SR-1ZnO/CP reached 7013 ± 215%. ZnO incorporation also improved mechanical performance, with CS/PVA/SR-2ZnO/CP displaying the highest tensile strength (39.18 ± 0.2 MPa) and elongation at break (9.54 ± 1.04%). ZnO incorporation also led to a concentration-dependent increase in antibacterial activity, with SR-based dressings achieving near-complete bacterial reduction at higher ZnO loadings. All the dressings demonstrated good biocompatibility, while CS/PVA/SR-1ZnOCP showed the fastest clotting time (420 s ± 40), highlighting its potential for hemostatic applications. Full article

Patient Blood Management (PBM) has evolved from a transfusion-centered practice to a structured, patient-focused perioperative strategy aimed at improving surgical outcomes while preserving blood resources. In the operating room, where bleeding risk is anticipated and modifiable, PBM requires proactive intervention rather than reactive transfusion. This review synthesizes current evidence on perioperative blood conservation strategies specifically relevant to surgeons and anesthesiologists. Preoperative optimization begins with systematic identification and correction of anemia, most commonly iron deficiency, using appropriately timed oral or intravenous iron therapy and, in selected cases, erythropoiesis-stimulating agents. Careful management of anticoagulant and antiplatelet therapies, early recognition of acquired or inherited coagulopathies, and protocol-driven reversal strategies further reduce perioperative hemorrhagic risk. Intraoperatively, blood conservation depends on meticulous surgical technique, respect for anatomical planes, minimally invasive approaches, and the judicious use of advanced energy devices and topical hemostatic agents. Pharmacologic interventions—particularly tranexamic acid administered with appropriate timing and dosing—have demonstrated consistent reductions in blood loss and transfusion requirements across multiple surgical disciplines. Goal-directed coagulation management guided by viscoelastic testing allows targeted correction of specific hemostatic deficits while minimizing unnecessary blood product exposure. Acute normovolemic hemodilution and intraoperative cell salvage provide additional benefit in selected high-blood-loss procedures. Collectively, these multimodal strategies shift perioperative care from product-driven transfusion toward physiology-based blood conservation. When embedded within institutional protocols and supported by multidisciplinary collaboration, perioperative PBM reduces transfusion exposure, decreases morbidity, shortens hospital stay, and promotes sustainable stewardship of blood resources without compromising patient safety. Full article

Hemostatic biomaterial agents are widely used during surgery and trauma care to control bleeding, yet their effects on wound healing remain incompletely understood. This study evaluated the impact of oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a gelatin-based hemostat (GELA) on wound healing at 14 and 30 days in a mouse model. Full-thickness wounds were created in C57BL/6J mice (n = 192) and compared to sham controls. Tissue samples were analyzed histologically, supported by immunohistochemistry for Ki-67 and α-SMA and qPCR for VEGF, TGF-β, and FGF-2. Histology demonstrated preserved tissue architecture across groups with progressive resorption of cellulose-based materials, whereas GELA showed localized fibrous structures and enhanced extracellular matrix formation. At day 14, no significant differences were observed in proliferation, contraction, VEGF, or FGF-2 expression; however, TGF-β was significantly reduced in the ORC group. By day 30, GELA significantly increased epidermal proliferation, while contraction markers were elevated in both GELA and ORC. VEGF expression was reduced in GELA and ORC, whereas ONRC showed increased TGF-β expression. FGF-2 remained unchanged across groups. All investigated hemostatic materials were well tolerated during the early postoperative phase (up to day 14), indicating short-term biocompatibility within the scope of this model. In contrast, material-specific differences in cellular activity and growth factor expression became apparent during the later remodeling phase (day 30). These findings suggest differential effects on cellular and molecular aspects of tissue remodeling; however, no conclusions can be drawn regarding overall healing quality or clinical safety, as no quantitative macroscopic or functional outcome measures were assessed. Full article

Oxidized cellulose (OC) and oxidized regenerated cellulose (ORC) are bioabsorbable polysaccharide-based materials widely used in surgery for topical hemostasis. Beyond their established hemostatic role, increasing attention has been directed toward their potential antimicrobial activity, primarily attributed to local acidification following carboxyl group dissociation. Discussing the possible implications of the antibacterial properties of OC/ORC in veterinary surgical practice, this review critically examines the existing evidence. In vitro studies show that viable bacterial counts are significantly reduced in both Gram-positive and Gram-negative pathogens, including antibiotic-resistant strains. Historical in vivo animal models further support a reduction in bacterial recovery in contaminated tissues treated with OC. However, contemporary veterinary clinical trials specifically evaluating surgical site infection (SSI) outcomes remain limited. Documented limitations include variability in formulation, quantity-dependent degradation kinetics, and the potential for foreign body reactions when excessive material is retained. Current evidence suggests that OC may provide adjunctive antimicrobial effects under controlled experimental conditions, primarily in vitro and in standardized animal models, but these properties should be interpreted with caution, and its role should be integrated within comprehensive infection prevention strategies rather than considered a substitute for established perioperative protocols. Full article

Background/Objectives: Patients with severe hemophilia A on prophylaxis with emicizumab exhibit a mild/moderate bleeding phenotype that requires the use of either recombinant FVIII (rFVIII) or bypassing agents (BPAs) in patients with inhibitors, in the case of breakthrough bleeding or surgery. Since factor IX (FIX) limits the formation of the FIXa–emicizumab–FX complex, exogenously added FIX might enhance complex formation and thrombin generation. This study aimed to compare the procoagulant effects of various FIX concentrates with recombinant activated FVII (rFVIIa), activated prothrombin complex concentrate (aPCC), and rFVIII in SHA patients with and without inhibitors under emicizumab prophylaxis. Methods: Hemostatic changes were monitored using two optimized global coagulation assays: rotational thromboelastometry and calibrated automated thrombin generation. Tubes containing corn trypsin inhibitor (CTI) were used during blood collection to prevent activation. Low concentrations of tissue factor (TF) were used to trigger coagulation in both assays. Results: Ex vivo addition of recombinant FIX concentrates significantly increased the procoagulant activity of emicizumab, achieving levels comparable to therapeutic doses of rFVIIa or rFVIII, and the proportion of active FIXa within the concentrates is a major contributor to their procoagulant function. We assessed the influence of FVIII inhibitors on the hemostatic efficacy of rFIX concentrates and BPAs, finding that rFIX-induced thrombin generation increased in the presence of inhibitors, and no significant differences were observed with BPAs. Conclusions: These findings suggest that FIX concentrates could be an effective alternative to BPAs for emicizumab-treated patients, particularly those with inhibitors. Further studies are needed to confirm their in vivo efficacy and to evaluate thrombotic risk. Full article

Background: Direct oral anticoagulants (DOACs) have transformed antithrombotic therapy but carry significant bleeding risks requiring prompt reversal. Recent regulatory changes have altered the reversal landscape, notably with the withdrawal of andexanet alfa from the U.S. market. Anticoagulation stewardship programs (ASPs) are essential for navigating this evolving environment and optimizing safe use of anticoagulants. Methods: This narrative review synthesizes evidence from landmark clinical trials (RE-VERSE AD, ANNEXA-4, ANNEXA-I), contemporary guidelines, emerging literature on reversal agents, and critical regulatory updates including the 2025 U.S Food and Drug Administration (FDA) withdrawal of andexanet alfa. Results: Idarucizumab remains the only FDA-approved specific antidote for dabigatran. Following the withdrawal of andexanet alfa, prothrombin complex concentrates (PCCs), both 4-factor and activated are now the primary reversal options for Factor Xa inhibitors, with recent evidence demonstrating comparable hemostatic efficacy. Ciraparantag, a universal reversal agent, is currently in Phase III development. Effective ASPs must now adapt protocols to the post-andexanet era while ensuring timely access to alternative reversal strategies. Conclusions: The reversal landscape has undergone a fundamental transformation with the loss of andexanet alfa. Success in DOAC-associated bleeding management now depends on optimizing PCC-based strategies, integrating systematic stewardship approaches, and preparing for emerging universal antidotes. Institutions must urgently update algorithms, ensure PCC availability, and monitor outcomes in this new therapeutic environment. Full article

This review presents an innovative and timely exploration of how cytoprotection can serve as a cohesive therapeutic approach by which to address the hemorrhage–thrombosis paradox. Presenting counteraction of both hemorrhage and thrombosis as phase-dependent outcomes of vascular dysregulation, the manuscript synthesizes conceptual, experimental, and clinical evidence into a unified systems-level model focused on the stable gastric pentadecapeptide BPC 157, which acts as a cytoprotective mediator. In rodents, BPC 157 can simultaneously counteract hemorrhage and thrombosis without directly affecting the coagulation cascade (aggregometry, thromboelastometry). This cytoprotective framework (decreased hemorrhage, decreased thrombosis) stands with presentation of both hemorrhage and thrombosis in the wound, arrhythmias, and Virchow triad, and resolution of these disturbances. As proof of the concept (full cytoprotective effect), a vasoprotective cytoprotective mediator capable of bidirectional regulation, BPC 157, is effective for wound healing, arrhythmia control, and normalization of Virchow’s triad (i.e., following major injuries, occlusion/occlusion-like syndromes). As a comparison from a cytoprotective (partial vs. full) standpoint, conventional agents—anticoagulants, antiplatelet drugs, and fibrinolytics—provide only partial protection by targeting isolated components of hemostasis. Beta blockers, calcium channel blockers, prostaglandins, NO modulators, ACE inhibitors, and statins each exert broader cytoprotective effects; however, these actions remain incomplete and context-dependent, typically unidirectional, dose-limited, or are achieved at the expense of opposing pathological risks. Contrarily, for BPC 157, decreased hemorrhage (including both anticoagulants and antiplatelet agents), decreased thrombosis, effective wound healing, arrhythmia control, and normalization of Virchow’s triad involve preservation of endothelial integrity, normalization of microcirculation, modulation of the NO system, stabilization of hemostatic balance, and recruitment of adaptive collateral pathways. Nevertheless, reliance on preclinical models necessitates further clinical validation. Full article

High-energy ballistic and avulsive injuries to the face represent some of the most complex challenges in modern reconstructive surgery. Since Robertson and Manson’s 1999 management protocol, extensive military experience and technological advancements have transformed the treatment principles while preserving the core tenets of staged care. This updated review synthesizes evidence from 36 studies published since 2000, encompassing over two decades of global experience in both military and civilian trauma. Advances in damage-control resuscitation, wound decontamination, and early skeletal stabilization have improved survival and functional outcomes. Modern imaging—particularly intraoperative CT and navigation—enables the precise verification of the reduction and removal of retained fragments, while virtual surgical planning and patient-specific implants allow the accurate restoration of facial buttresses. Early vascularized tissue transfer has reduced contracture and infection rates. Adjuncts such as hyperbaric oxygen therapy, permissive hypotension, and advanced hemostatic agents further optimize recovery. The updated four-phase protocol—resuscitation, reconstitution, reconstruction, and rehabilitation—emphasizes early definitive repair, multidisciplinary collaboration, and the integration of digital planning. These refinements extend Robertson and Manson’s foundational principles into the era of precision surgery, achieving superior aesthetic and functional outcomes for patients with devastating facial injuries. Full article

Bone regeneration focuses on the creation of functional tissue to repair bone defects. Creating a biodegradable scaffold hydrogel that combines a hemostatic agent with bioactive ceramics can afford the biological and mechanical benefits of both components. In the present study, we developed an injectable gelatin–alginate dual-composite hydrogel, loaded with two functional fillers: hydroxyapatite (HA) and the hemostatic agent montmorillonite (MMT). HA (microparticles and nanoparticles) was incorporated at concentrations of 10–30 mg/mL, with and without MMT at 20 mg/mL. The effects of functional fillers and their concentration on the microstructure and resulting physical and mechanical properties were studied, and a qualitative model summarising these effects was developed. All formulations exhibited clinically appropriate gelation times (5–29 s). n-HA significantly prolonged gelation time, reaching 29 ± 3 s at 30 mg/mL, while MMT reduced gelation time at all concentrations. The tensile strength of the unloaded hydrogel reached 20 kPa and increased to 57 kPa with 30 mg/mL of n-HA. The tensile strength even increased further with the addition of MMT (77 kPa). The results indicate that the combination of HA and MMT produced dual micro-composite hydrogels with moderate reinforcement, whereas the combination of n-HA and MMT generated dual nano–micro composites with combined reinforcing effects. The latter exhibited the highest strength and sealing ability while maintaining clinically relevant gelation times and controlled swelling behaviour. In conclusion, the combination of MMT with n-HA or HA enables the creation of functional hydrogels with controlled properties, tailored to specific applications in bone regeneration. Full article