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Uncontrolled exsanguination remains the leading cause of death for trauma patients, many of whom die in the pre-hospital setting. Without expedient intervention, trauma-associated hemorrhage induces a host of systemic responses and acute coagulopathy of trauma. For this reason, health care providers and prehospital personal face the challenge of swift and effective hemorrhage control. The utilization of adjuncts to facilitate hemostasis was first recorded in 1886. Commercially available products haves since expanded to include topical hemostats, surgical sealants, and adhesives. The ideal product balances efficacy, with safety practicality and cost-effectiveness. This review of hemostasis provides a guide for successful implementation and simultaneously highlights future opportunities.

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We demonstrate that "nanofactory"-loaded biopolymer capsules placed in the midst of a bacterial population can direct bacterial communication. Quorum sensing (QS) is a process by which bacteria communicate through small-molecules, such as autoinducer-2 (AI-2), leading to collective behaviors such as virulence and biofilm formation. In our approach, a "nanofactory" construct is created, which comprises an antibody complexed with a fusion protein that produces AI-2. These nanofactories are entrapped within capsules formed by electrostatic complexation of cationic (chitosan) and anionic (sodium alginate) biopolymers. The chitosan capsule shell is crosslinked by tripolyphosphate (TPP) to confer structural integrity. The capsule shell is impermeable to the encapsulated nanofactories, but freely permeable to small molecules. In turn, the capsules are able to take in substrates from the external medium via diffusion, and convert these via the nanofactories into AI-2, which then diffuses out. The exported AI-2 is shown to stimulate QS responses in vicinal Escherichia coli. Directing bacterial population behavior has potential applications in next-generation antimicrobial therapy and pathogen detection. We also envision such capsules to be akin to artificial "cells" that can participate in native biological signaling and communicate in real-time with the human microbiome. Through such interaction capabilities, these "cells" may sense the health of the microbiome, and direct its function in a desired, host-friendly manner.

Hm-chitosan is superior to unmodified chitosan sponges (p < 0.001) or standard gauze for controlling bleeding from a lethal arterial injury. The hm-chitosan technology may provide an advantage over native chitosan-based dressings for control of active hemorrhage.

We describe a new class of hierarchical containers that are formed via single-step assembly and, at a later time, self-destruct because of their packaged contents. These containers are spherical capsules formed by electrostatic complexation of the anionic biopolymer, gellan gum, with the cationic biopolymer, chitosan. The capsules are termed "motherships" and are engineered to carry a cargo of much smaller containers (e.g., nanoscale liposomes ("babyships")), within their lumen. Additionally, we package an enzyme, chitosanase, in the capsule that is capable of degrading polymeric chitosan into short oligomers. Thereby, we create motherships that self-destruct, liberating their cargo of babyships into the external solution. The time scale for self-destruction can be engineered based on the internal concentration of enzyme. The motherships are stable when stored in a freeze-dried form and can be readily dispersed into water or buffer solutions at a later time, whereupon their "internal clock" for self-destruction is initiated. The above concept could be useful for the triggered release of a variety of payloads including drugs, biological therapeutics, cosmetics, and flavor ingredients.

Hemorrhage (severe blood loss) from traumatic injury is a leading cause of death for soldiers in combat and for young civilians. In some cases, hemorrhage can be stopped by applying compression of a tourniquet or bandage at the injury site. However, the majority of hemorrhages that prove fatal are "non-compressible", such as those due to an internal injury in the truncal region. Currently, there is no effective way to treat such injuries. In this initial study, we demonstrate that a sprayable polymer-based foam can be effective at treating bleeding from soft tissue without the need for compression. When the foam is sprayed into an open cavity created by injury, it expands and forms a self-supporting barrier that counteracts the expulsion of blood from the cavity. The active material in this foam is the amphiphilic biopolymer, hydrophobically modified chitosan (hmC), which physically connects blood cells into clusters via hydrophobic interactions (the hemostatic mechanism of hmC is thus distinct from the natural clotting cascade, and it works even with heparinized or citrated blood). The amphiphilic nature of hmC also allows it to serve as a stabilizer for the bubbles in the foam. We tested the hmC-based hemostatic foam for its ability to arrest bleeding from an injury to the liver in pigs. Hemostasis was achieved within minutes after application of the hmC foams (without the need for external compression). The total blood loss was 90% lower with the hmC foam relative to controls.

We describe a new way to impart pH-responsive properties to gels of biopolymers such as gelatin. This approach involves the embedding of pH-sensitive nanosized vesicles within the gel. The vesicles employed here are those of sodium oleate (NaOA), a fatty-acid-based amphiphile with a single C18 tail. In aqueous solution, NaOA undergoes a transition from vesicles at a pH approximately 8 to micelles at a pH higher than approximately 10. Here, we combine NaOA and gelatin at pH 8.3 to create a vesicle-loaded gel and then bring the gel in contact with a pH 10 buffer solution. As the buffer diffuses into the gel, the vesicles within the gel get transformed into micelles. Accordingly, a vesicle-micelle front moves through the gel, and this can be visually identified by the difference in turbidity between the two regions. Vesicle disruption can also be done in a spatially selective manner to create micelle-rich domains within a vesicle-loaded gel. A possible application of the above approach is in the area of pH-dependent controlled release. A vesicle-to-micelle transition releases hydrophilic solutes encapsulated within the vesicles into the bulk gel, and in turn these solutes can rapidly diffuse out of the gel into the external bath. Experiments with calcein dye confirm this concept and show that we can indeed use the pH in the bath to tune the release rate of solutes from vesicle-loaded gels.