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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

Extraterrestrial Hemorrhage Control: Terrestrial Developments in Technique, Technology, and Philosophy with Applicability to Traumatic Hemorrhage in Space

Managing injury and illness during long duration space flight limits efforts to explore beyond low earths orbit. Traumatic injury may be expected to occur in space and is a frequent cause of preventable deaths, often related to uncontrolled or ongoing hemorrhage (H). Such bleeding causes 40% of terrestrial injury mortality. Current guidelines emphasize early control of H compared to intravenous infusions. Recent advances in surgical and critical care may be applicable to trauma care in space, with appropriate considerations of the extreme logistical and personnel limitations. Methods: Recent developments in technique, resuscitation fluids, hemoglobin (Hb) substitutes, hemostatic agents, interventional angiography, damage control principles, and concepts related to suspended animation were reviewed. Results: H associated with instability frequently requires definitive intervention. Direct pressure should be applied to all compressible bleeding, but novel approaches are required for intracavitary noncompressible bleeding. Intravenous hemostatic agents such as recombinant Factor VII may facilitate hemostasis especially when combined with a controlled hypotension approach. Both open and laparoscopic techniques could be used in weightlessness, but require technical expertise not likely to be available. Specific rehearsed invasive techniques such as laparotomy with packing, or arterial catherterization with with robotic intravascular embolization might be considered . Hemodynamic support, thermal manipulation, or pharmacologic induction of a state of metabolic down regulation for whole body preservation may be appropriate. Hypertonic saline, with or without dextran, may temporize vascular support and decrease reperfusion injury, with less mass than other solutions. Hb substitutes have other theoretical advantages. Conclusions: Terrestrial developments suggest potential novel strategies to control H in space, but will required a coordinated program of evaluation and training to evaluate.

Kirkpatrick, Andrew

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