Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “hemostats”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

11 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Nanoengineered Shape-Memory Hemostat

Uncontrolled hemorrhage is the predominant cause of preventable combat deaths. Various biomaterials serve as hemostatic agents due to their procoagulant or absorptive activity. However, these biomaterials often lack expansion capabilities, which severely limits use in noncompressible wounds. This study combines a hemostatic nanocomposite with a shape-memory polymer foam to design a composite material with both hemostatic and physical expansion properties. This composite is fabricated in two formulations: a foam externally coated in a highly concentrated nanocomposite (“coated composite”) and a foam containing a diluted nanocomposite infused throughout its pores (“infused composite”). Both formulations retain the shape-memory foam's expansion property. Further, the coated composite shows improved fluid uptake (>2-fold) versus infused composites or foam. The nanocomposite component dissociates from the foam under degradative conditions, with the foam remaining stable for 30 days. Hemostatic studies illustrate that the coated composite reduces the clotting time by ≈20%. Alternatively, the infused composite improves clotting over a larger distance (up to ≈2× distance from the composite). These results signify a modular hemostatic ability: the coated composite reduces clotting and improves fluid uptake, while the infused composite achieves diffuse clotting and maintains mechanical properties. Thus, these materials pose a strong potential for use in noncompressible wounds.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated, with no adverse events. • Overall, human fibrinogen concentrate demonstrated a good safety profile. • This data adds to the safety information available to date on this hemostatic agent.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Percutaneous BioOrganic Sealing of Duodenal Fistulas: Case Report and Review of Biological Sealants with Potential Use in Interventional Radiology

Biological sealants are being increasingly used in a variety of surgical specialties for their hemostatic and sealing capabilities. However, their use in interventional radiology has not been widely reported. The authors describe a case of duodenal perforation occurring after 15 years of gastric bypass surgery, in whom surgical diversion was unsuccessfully attempted and the leakage was successfully controlled using percutaneous administration of a combination of biological and organic sealants.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Transcatheter Arterial Embolization for Gastrointestinal Bleeding Secondary to Gastrointestinal Lymphoma

PurposeTo evaluate the effectiveness of transcatheter arterial embolization (TAE) for gastrointestinal (GI) bleeding caused by GI lymphoma.Materials and MethodsThe medical records of 11 patients who underwent TAE for GI bleeding caused by GI lymphoma between 2001 and 2015 were reviewed retrospectively.ResultsA total of 20 TAE procedures were performed. On angiography, contrast extravasation, and both contrast extravasation and tumor staining were seen in 95 % (19/20) and 5 % (1/20) of the procedures, respectively. The most frequently embolized arteries were jejunal (n = 13) and ileal (n = 5) branches. Technical and clinical success rates were 100 % (20/20) and 27 % (3/11), respectively. The causes of clinical failure in eight patients were rebleeding at new sites. In four patients who underwent repeat angiography, the bleeding focus was new each time. Three patients underwent small bowel resection due to rebleeding after one (n = 2) or four (n = 1) times of TAEs. Another two patients underwent small bowel resection due to small bowel ischemia/perforation after three or four times of TAEs. The 30-day mortality rate was 18 % due to hypovolemic shock (n = 1) and multiorgan failure (n = 1).ConclusionAngiogram with TAE shows limited therapeutic efficacy to manage GI lymphoma-related bleeding due to high rebleeding at new sites. Although TAE can be an initial hemostatic measure, surgery should be considered for rebleeding due to possible bowel ischemic complication after repeated TAE procedures.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Systematic mapping of the conformational landscape and dynamism of soluble fibrinogen

Background: Fibrinogen is a soluble, multisubunit, and multidomain dimeric protein, which, upon its proteolytic cleavage by thrombin, is converted to insoluble fibrin, initiating polymerization that substantially contributes to clot growth. Fibrinogen contains numerous, transiently accessible “cryptic” epitopes for hemostatic and immunologic proteins, suggesting that fibrinogen exhibits conformational flexibility, which may play functional roles in its temporal and spatial interactions. Hitherto, there have been limited integrative approaches characterizing the solution structure and internal flexibility of fibrinogen. Methods: Here, utilizing a multipronged, biophysical approach involving 2 solution-based techniques, temperature-dependent hydrogen-deuterium exchange mass spectrometry and small angle X-ray scattering, corroborated by negative stain electron microscopy, we present a holistic, conformationally dynamic model of human fibrinogen in solution. Results: Our data reveal 4 major and distinct conformations of fibrinogen accommodated by a high degree of internal protein flexibility along its central scaffold. We propose that the fibrinogen structure in the solution consists of a complex, conformational landscape with multiple local minima. This is further supported by the location of numerous point mutations that are linked to dysfibrinogenemia and posttranslational modifications, residing near the identified fibrinogen flexions. Conclusion: Further, this work provides a molecular basis for the structural “dynamism” of fibrinogen that is expected to influence the broad swath of its functionally diverse macromolecular interactions and fine-tune the structural and mechanical properties of blood clots.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Von Willebrand factor deficiency reduces liver fibrosis in mice

Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet-adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general population, the role of VWF in acute and chronic liver injury has not been examined in depth in experimental settings. We tested the hypothesis that VWF deficiency inhibits experimental liver injury and fibrosis. Wild-type (WT) and VWF-deficient mice were challenged with carbon tetrachloride (CCl{sub 4}) and the impact of VWF deficiency on acute liver injury and chronic liver fibrosis was determined. VWF deficiency did not significantly affect acute CCl{sub 4}-induced hepatocellular necrosis in mice. Chronic CCl{sub 4} challenge, twice weekly for 6 weeks, significantly increased hepatic stellate cell activation and collagen deposition in livers of WT mice. Interestingly, hepatic induction of several profibrogenic and stellate cell activation genes was attenuated in VWF-deficient mice. Moreover, birefringent sirius red staining (indicating type I and III collagens) and type I collagen immunofluorescence indicated a reduction in hepatic collagen deposition in CCl{sub 4}-exposed VWF-deficient mice compared to CCl{sub 4}-exposed WT mice. The results indicate that VWF deficiency attenuates chronic CCl{sub 4}-induced liver fibrosis without affecting acute hepatocellular necrosis. The results are the first to demonstrate that VWF deficiency reduces the progression of liver fibrosis, suggesting a mechanistic role of elevated plasma VWF levels in cirrhosis. - Highlights: • Plasma von Willebrand Factor (VWF) levels increase in experimental liver damage. • VWF contributes to liver myofibroblast activation in experimental fibrosis. • VWF deficiency reduces experimental fibrosis without affecting acute liver injury.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Tough, Rapidly Swelling Thermoplastic Elastomer Hydrogels for Hemorrhage Control

We present a novel elastomer with an amphiphilic triblock/graft architecture, allowing it to rapidly swell in water and form a tough hydrogel. The design was motivated by uncontrolled hemorrhage, responsible for 80–90% of potentially survivable deaths of US soldiers over the past 15 years. The polymer is 5.7 times as absorbent and 3 times as tough as a state of the art gauze-based hemostatic dressing. It swells to equilibrium within seconds in phosphate buffered saline due to a microphase-separated morphology featuring a continuous mobile ionic phase supported by hydrophobic glassy domains and rubbery linkages, as observed by transmission electron microscopy and small-angle neutron scattering. Thickness-dependent swelling is as much as an order of magnitude faster than many tough hydrogels in the literature, yet toughness is comparable as a function of water content. Furthermore, the polymer is combined with gauze to form a rapidly swelling, fiber-reinforced hydrogel composite with promising mechanical properties.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Antimicrobial Peptides Can Facilitate Whole Blood Safety from Bacteria: A Proof of Concept

With continuous improvements to blood donor deferrals and the availability of sensitive tests for donation screening for infectious agents, bacterial contamination of whole blood (WB) and blood components stored for transfusion is a rare event. Nonetheless, it still occurs and remains a transfusion-associated risk in terms of septic transfusion reactions (STRs) and transfusion-transmitted bacterial infections with morbidity and mortality outcomes. One of the risk mitigation strategies for bacterial contamination is to implement treatment with currently available proactive pathogen reduction technologies (PRTs) for these transfusion products. Here, as a proof of concept, we tested two recently developed unique cationic antimicrobial peptides (AMPs; D-CONGA and D-CONGA-Q7) for WB safety from bacterial contamination. In this study, WB was inoculated with Escherichia coli and Staphylococcus epidermidis and treated with the two peptides to evaluate their bactericidal efficacy. The results demonstrated that D-CONGA and D-CONGA-Q7 exhibit potent inhibitory activity against the bacteria with a minimal inhibitory concentration (MIC) range of 4–8 and 1–8 μM, respectively, depending on the bacterial species tested. Time-kill kinetics further confirmed that the peptides exhibit bactericidal efficacy at 8 μM by achieving a 5-log 10 reduction (99.999%) of the bacterial load in WB with a time-dependent killing profile. Furthermore, even at 20 μM, the AMPs did not negatively impact hemolysis or hemostatic properties. We have further demonstrated using a cationic exchange resin that the cationic AMPs can be separated and removed from WB after the peptide treatments. During 35-day WB storage at 2–8 °C, 4 μM D-CONGA-Q7 one-time treatment prevented S. epidermidis growth and preserved WB quality and integrity. Overall, the results described here provide the first proof of concept that certain AMPs, such as D-CONGA and D-CONGA-Q7, can facilitate WB safety from bacteria during storage.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Mutational Constraints on Local Unfolding Inhibit the Rheological Adaptation of von Willebrand Factor

Unusually large von Willebrand factor (VWF), the first responder to vascular injury in primary hemostasis, is designed to capture platelets under the high shear stress of rheological blood flow. In type 2M von Willebrand disease, two rare mutations (G1324A and G1324S) within the platelet GPIbα binding interface of the VWF A1 domain impair the hemostatic function of VWF. We investigate structural and conformational effects of these mutations on the A1 domain's efficacy to bind collagen and adhere platelets under shear flow. These mutations enhance the thermodynamic stability, reduce the rate of unfolding, and enhance the A1 domain's resistance to limited proteolysis. Collagen binding affinity is not significantly affected indicating that the primary stabilizing effect of these mutations is to diminish the platelet binding efficiency under shear flow. The better stability stems from the steric consequences of adding a side chain (G1324A) and additionally a hydrogen bond (G1324S) to His 1322 across the β2-β3 hairpin in the GPIbα binding interface, which restrains the conformational degrees of freedom and the overall flexibility of the native state. These studies reveal a novel rheological strategy in which the incorporation of a single glycine within the GPIbα binding interface of normal VWF enhances the probability of local unfolding that enables the A1 domain to conformationally adapt to shear flow while maintaining its overall native structure.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structural analysis of platelet fragments and extracellular vesicles produced by apheresis platelets during storage

Platelets (PLTs) for transfusion can be stored for up to 7 days at room temperature (RT). The quality of apheresis PLTs decreases over storage time, which affects PLT hemostatic functions. Here, we characterized the membranous particles produced by PLT storage lesion (PSLPs), including degranulated PLTs, PLT ghosts, membrane fragments, and extracellular membrane vesicles (PEVs). The PSLPs generated in apheresis platelet units were analyzed on days 1, 3, 5, and 7 of RT storage. A differential centrifugation and a sucrose density gradient were used to separate PSLP populations. PSLPs were characterized using scanning and transmission electron microscopy (EM), flow cytometry (FC), and nanoparticle tracking analysis (NTA). PSLPs have different morphologies and a broad size distribution; FC and NTA showed that the concentration of small and large PSLPs increases with storage time. The density gradient separated 3 PSLP populations: (1) degranulated PLTs, PLT ghosts, and large PLT fragments; (2) PEVs originated from PLT activation and organelles released by necrotic PLTs; and (3) PEV ghosts. Most PSLPs expressed phosphatidyl serine and induced thrombin generation in the plasma. PSLPs contained extracellular mitochondria and some had the autophagosome marker LC3. PSLPs encompass degranulated PLTs, PLT ghosts, large PLT fragments, large and dense PEVs, and low-density PEV ghosts. The activation-related PSLPs are released, particularly during early stage of storage (days 1-3), and the release of apoptosis- and necrosis-related PSLPs prevails after that. No elevation of LC3- and TOM20-positive PSLPs indicates that the increase of extracellular mitochondria during later-stage storage is not associated with PLT mitophagy.

59 BASIC BIOLOGICAL SCIENCES↗