Noncompressible Hemorrhage Research Articles

A Self-Assembly Pro-Coagulant Powder Capable of Rapid Gelling Transformation and Wet Adhesion for the Efficient Control of Non-Compressible Hemorrhage.

Rapid and effective control of non-compressible massive hemorrhage poses a great challenge in first-aid and clinical settings. Herein, a biopolymer-based powder is developed for the control of non-compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross-linking based on "click" chemistry and Schiff base reaction upon contact with the blood, leading to rapid self-gelling. It also exhibits robust tissue adhesion through covalent/non-covalent interactions with the tissues (adhesive strength: 89.57±6.62KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non-compressible hemorrhage.

Robust adhesive nanocomposite sponge composed of citric acid and nano clays modified cellulose for rapid hemostasis of lethal non-compressible hemorrhage

Massive bleeding control plays the main role in saving people's lives in emergency situations. Herein, modified cellulose-based nanocomposite sponges by polydopamine (PDA) and laponite nano-clay was developed to sturdily deal with non-compressible lethal severe bleeding. PDA accomplishes supreme adhesion in the bleeding site (∼405 kPa) to form strong physical barrier and seal the position. Sponges super porous (∼70 % porosity) and super absorbent capacity (48 g blood absorbed per 1 g sponge) by concentrating the blood cells and platelets provides the requirements for primary hemostasis. Synergistically, the nanocomposite sponges' intelligent chemical structure induces hemostasis by activation of the XI, IX, X, II and FVII factors of intrinsic and extrinsic coagulation pathways. Excellent hemostatic performance of sponges in-vitro was assessed by RBC accumulation (∼100 %), blood clotting index (∼10 %), platelet aggregation/activation (∼93 %) and clotting time. The nanocomposite sponges depicted super performance in the fatal high-pressure non-compressible hemorrhage model by reducing of >2, 15 and 3 times in the bleeding amount at New Zealand rabbit's heart and liver, and rat's femoral artery bleeding models, respectively compared to commercial hemostatic agents (Pvalue˂0.001). The in-vivo host response results exhibited biosafety with no systemic and significant local inflammatory response by hematological, pathological and biochemical parameters assessments.

Hemostatic, antibacterial, conductive and vascular regenerative integrated cryogel for accelerating the whole wound healing process

The entire process of wound healing, involving hemostasis, inflammation, proliferation, and remodeling, relies on various cell types and variables interaction in a very complicated temporal and spatial sequence, and this complex process faces serious challenges. Thus, it is necessary to develop wound dressings that can adapt to the different stages of the healing process. In this study, methacrylic anhydride-modified gelatin (GM), β-cyclodextrin modified reduced graphene oxide (rGO-CD), 1-vinylimidazole (VI), and zin ion (Zn2+) were combined to prepare GVG-Zn cryogels through radical polymerization, host–guest interaction, and ionic coordination. The cryogels exhibited enhanced mechanical strength, fatigue resistance, inter-connected porous structure, rapid expansion property, conductivity, biocompatibility, and photothermal antibacterial properties (above 99 % killing ratios of both E. coli and MRSA after NIR light irradiation 3 min). Furthermore, the cryogels showed excellent hemostasis in the non-compressible mouse liver hemorrhage model, compared with gauze and gelatin sponges. When the cryogel groups treated MRSA-infected full-thickness skin defected wounds, it showed less inflammatory infiltration, more collagen deposition, and induced angiogenesis, compared with the commercial dressings (Tegaderm™ film and Cosmopor®). The results indicated that GVG-Zn cryogels have good potential in non-compressible hemorrhage and wound healing.

Chitosan based Janus cryogel with anisotropic wettability, antibacterial activity, and rapid shape memory for effective hemostasis

Excessive bleeding and bacterial infection leading to death is a major concern worldwide, particularly in cases of deep and narrow noncompressible hemorrhage. Herein, a novel Janus cryogel with anisotropic surface wettability, antibacterial activity, and rapid shape recovery was designed by constructing a hydrophilic porous cryogel using chitosan (CS), acacia gum (AG), and quaternized mesoporous bioglass (QMBG), with subsequent surface hydrophobic modification using octadecanol. The asymmetric hydrophobic surface modification of octadecanal endowed OCAQ with outstanding antiblood and antibacterial permeability, effectively preventing blood outflow and the invasion of bacteria to the wound. The hydrophilic parts with interconnected macroporous structure give the cryogel with ultra-high water uptake (5167 ± 182 %) and rapid water-trigged shape recover ability (≈2.1 s). The presence of active CS, AG, and QMBG in cryogel contributes to its exceptional blood clotting ability. Janus cryogel presents outstanding hemostatic performance (0.14 ± 0.03 g) in rat's liver injury model. Moreover, Janus cryogel exhibits excellent antibacterial properties due to the combination of its hydrophobic surface and antimicrobial quaternary amine groups. Meanwhile, the Janus cryogel has favorable hemocompatibility and biocompatibility. A Therefore, the Janus cryogel will become a candidate with great potential for clinical application of noncompressible wound as a multifunctional dressing.

Evaluation of hemostatic devices in a randomized porcine model of junctional hemorrhage and 72-hour prolonged field care.

Hemorrhage control in prolonged field care (PFC) presents unique challenges that drive the need for enhanced point of injury treatment capabilities to maintain patient stability beyond the Golden Hour. To address this, two hemostatic agents, Combat Gauze (CG) and XSTAT, were evaluated in a porcine model of uncontrolled junctional hemorrhage for speed of deployment and hemostatic efficacy over 72 hours. The left subclavian artery and subscapular vein were isolated in anesthetized male Yorkshire swine (70-85 kg) and injured via 50% transection, followed by 30 seconds of hemorrhage. Combat Gauze (n = 6) or XSTAT (n = 6) was administered until bleeding stopped and remained within subjects for observation over 72 hours. Physiologic monitoring, hemostatic efficacy, and hematological parameters were measured throughout the protocol. Gross necropsy and histology were performed following humane euthanasia. Both CG and XSTAT maintained hemostasis throughout the full duration of the protocol. There were no significant differences between groups in hemorrhage volume (CG: 1021.0 ± 183.7 mL vs. XSTAT: 968.2 ± 243.3 mL), total blood loss (CG: 20.8 ± 2.7% vs. XSTAT: 20.1 ± 5.1%), or devices used (CG: 3.8 ± 1.2 vs. XSTAT: 5.3 ± 1.4). XSTAT absorbed significantly more blood than CG (CG: 199.5 ± 50.3 mL vs. XSTAT: 327.6 ± 71.4 mL) and was significantly faster to administer (CG: 3.4 ± 1.6 minutes vs. XSTAT: 1.4 ± 0.5 minutes). There were no significant changes in activated clot time, prothrombin time, or international normalized ratio between groups or compared with baseline throughout the 72-hour protocol. Histopathology revealed no evidence of microthromboemboli or disseminated coagulopathies across evaluated tissues in either group. Combat Gauze and XSTAT demonstrated equivalent hemostatic ability through 72 hours, with no overt evidence of coagulopathies from prolonged indwelling. In addition, XSTAT offered significantly faster administration and the ability to absorb more blood. Taken together, XSTAT offers logistical and efficiency advantages over CG for immediate control of junctional noncompressible hemorrhage, particularly in a tactical environment. In addition, extension of indicated timelines to 72 hours allows translation to PFC.

Adenosine, lidocaine and Mg2+ update: teaching old drugs new tricks.

If a trauma (or infection) exceeds the body's evolutionary design limits, a stress response is activated to quickly restore homeostasis. However, when the injury severity score is high, death is often imminent. The goal of this review is to provide an update on the effect of small-volume adenosine, lidocaine and Mg2+ (ALM) therapy on increasing survival and blunting secondary injury after non-compressible hemorrhagic shock and other trauma and infective/endotoxemic states. Two standout features of ALM therapy are: (1) resuscitation occurs at permissive hypotensive blood pressures (MAPs 50-60 mmHg), and (2) the drug confers neuroprotection at these low pressures. The therapy appears to reset the body's baroreflex to produce a high-flow, hypotensive, vasodilatory state with maintained tissue O2 delivery. Whole body ALM protection appears to be afforded by NO synthesis-dependent pathways and shifting central nervous system (CNS) control from sympathetic to parasympathetic dominance, resulting in improved cardiovascular function, reduced immune activation and inflammation, correction of coagulopathy, restoration of endothelial glycocalyx, and reduced energy demand and mitochondrial oxidative stress. Recently, independent studies have shown ALM may also be useful for stroke, muscle trauma, and as an adjunct to Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). Ongoing studies have further shown ALM may have utility for burn polytrauma, damage control surgery and orthopedic surgery. Lastly, we discuss the clinical applications of ALM fluid therapy for prehospital and military far-forward use for non-compressible hemorrhage and traumatic brain injury (TBI).

An ultrafast water absorption composite cryogel containing Iron-doped bioactive glass with rapid hemostatic ability for non-compressible and coagulopathic bleeding

Traditional hemostatic materials have limited hemostatic effect on non-compressible wound, that is likely to develop into coagulopathy and leads to high mortality. As a powerful hemostatic material, in addition to having the function of forming solid physical barriers and effectively activating coagulation factors to rapidly control hemostasis, it should also has the ability to bypass the coagulation pathway to handle the bleeding of coagulopathic patients. In this work, we designed a QCOC composite cryogel by gelation of quaternized chitosan (QCS) and hydroxyethyl cellulose oxide (OHEC) at low temperature. Meanwhile, iron-doped bioactive glass (FeBG) as an active substance was introduced into the QCOC composite cryogel to promote erythrocyte aggregation by ion dissolution and activate intrinsic and extrinsic pathways. QCOC/FeBG composite cryogel had interconnected macroporous structure, ultrafast water absorption performance (reaching water absorption saturation in 4 s) and good shape memory properties (restoring to its original shape in 1 s). Additionally, the composite cryogel showed excellent antibacterial properties against S. aureus and E. coli as well as good cell biocompatibility. Furthermore, the QCOC/FeBG composite cryogel showed excellent hemostatic performance in the model of liver non-compressible hemorrhage with coagulation disorders, and the hemostasis time and blood loss were 60.87 ± 2.09 s and 366.38 ± 32.69 mg respectively, which were much lower than commercial gelatin sponge (196.62 ± 19.02 s and 1439.37 ± 165.27 mg). These results proved that QCOC/FeBG composite cryogel has excellent hemostatic properties, antibacterial properties, portability and usability, indicating a great potential as a timely hemostatic material in daily civil and military hemostasis.

Evaluation of novel hemostatic agents in a coagulopathic swine model of junctional hemorrhage.

Hemostatic dressings are used extensively in both military and civilian trauma to control lethal noncompressible hemorrhage. The ideal topical hemostatic agent would provide reliable hemostasis in patients with profound acidosis, coagulopathy, and shock. This study aimed to compare next-generation hemostatic agents against the current military standard in a translational swine model of vascular injury and coagulopathy. Female Yorkshire swine were randomized to eight groups (total n = 63; control n = 14, per group n = 7) of hemostatic agents and included: QuikClot Combat Gauze (Teleflex, Morrisville, NC), which served as the control; BloodSTOP IX (LifeScience Plus, Mountain View, CA); Celox Rapid (Medtrade Product, Crewe, United Kingdom); ChitoSAM 100 (Sam Medical, Tualatin, OR); EVARREST Fibrin Sealant Patch (Ethicon, Raritan, NJ); TAC Wrapping Gauze (H&H Medical, Williamsburg, VA); ChitoGauze XR Pro (Tricol Biomedical, Portland, OR); and X-Stat 30 (RevMedX, Wilsonville, OR). Hemodilution via exchange transfusion of 6% hetastarch was performed to induce acidosis and coagulopathy. An arteriotomy was created, allowing 30 seconds of free bleeding followed by application of the hemostatic agent and compression via an external compression device. A total of three applications were allowed for continued/recurrent bleeding. All blood loss was collected, and hemostatic agents were weighed to calculate blood volume loss. Following a 180-minute observation period, angiography was completed to evaluate for technical complication and distal perfusion of the limb. Finally, the limb was ranged five times to assess for rebleeding and clot stability. All swine were confirmed coagulopathic with rotational thromboelastography and acidotic (pH 7.2 ± 0.02). BloodSTOP IX allowed a significant increase in blood loss and number of applications required to obtain hemostasis compared with all other groups. BloodSTOP IX demonstrated a decreased survival rate (29%, p = 0.02). All mortalities were directly attributed to exsanguination as a result of device failure. In surviving animals, there was no difference in extravasation. BloodSTOP IX had an increased rebleeding rate after ranging compared with QuikClot Combat Gauze ( p = 0.007). Most novel hemostatic agents demonstrated comparable efficacy compared with the currently military standard hemostatic dressing, CG.

Benzeneboronic−alginate/quaternized chitosan−catechol powder with rapid self-gelation, wet adhesion, biodegradation and antibacterial activity for non-compressible hemorrhage control

Although hemostatic powders have excellent adaptability for irregular and inaccessible wounds, their hemostasis for continuous bleeding or bleeding wounds of non-compressible organs remains a critical challenge. Herein, a series of benzeneboronic acid-modified sodium alginate/catechol-modified quaternized chitosan (SA-BA/QCS-C, SBQCC) powders is developed by borate ester crosslinking for non-compressible hemorrhage control. SBQCC powders possess remarkable tissue adhesion, rapid self-gelation, good cytocompatibility and antibacterial activity against S. aureus and E. coil. The blood coagulation assays show that SBQCC powders display excellent blood clotting ability due to the synergistic effect of SA-BA and QCS-C. The SBQCC2 powder with the SA-BA to QCS-C mass ratio of 5 to 3 has the greatest effect on the blood-clotting rate. Upon depositing SBQCC2 powder to bleeding wounds of rabbit liver, the powder can absorb a large amount of blood and form a stable hydrogel physical barrier at the bleeding wounds in situ to achieve non-pressing rapid hemostasis. The SBQCC2 powder also has good biocompatibility and can be degraded in vivo. Altogether, the SBQCC powders can be a promising candidate for rapid hemostasis, and these findings may provide a new perspective for improving the hemostatic efficiency of the hemostatic powder in biomedical fields.

Engineered Bicomponent Adhesives with Instantaneous and Superior Adhesion Performance for Wound Sealing and Healing Applications

AbstractSurgical adhesives are playing an important role in wound repair and emergency hemostasis in clinical treatment. However, the development of strong bioglue with rapid in situ adhesion, durable adhesiveness, and flexibility in dynamic and moist physiological environments is still challenging. Herein, a new type of biosynthetic protein bioadhesives with superior adhesion performance is reported by developing a protein aldimine condensation strategy. Lysine‐rich recombinant proteins are designed and massively biosynthesized to instantaneously react with aldehyde cross‐linkers to realize in situ strong adhesion. The obtained bioadhesives show an ultra‐high adhesion strength of ≈101.6 kPa on porcine skin, outperforming extant clinical bioglues. In addition, they possess super biocompatibility, flexibility, biodegradability, and compliance with the tissues. Owing to the strong and instantaneous adhesion properties, the bioadhesives are qualified for dynamic wound closure, facilitating wound repair, and noncompressible hemorrhage. Importantly, they can be industrially encapsulated into custom‐made cartridge delivery tubes at low cost for clinical use. Therefore, biosynthetic bioadhesives have great potential for biological applications and are capable of scaling up to the industrial level for clinical transformation, which will be a successful paradigm for reforming existing clinical products.

Flexible dual-functionalized hyaluronic acid hydrogel adhesives formed in situ for rapid hemostasis

Hydrogel adhesives integrating both rapid and strong adhesion to blooding tissues and biocompatibility are highly desired for fast hemostasis. Herein, a flexible hyaluronic acid hydrogel adhesive is fabricated via photocrosslinking of the solution originating from dopamine-conjugated maleic hyaluronic acid (DMHA) in situ. The introduction of acrylate groups with high substitutions into the hydrogel matrix endows the adhesive with rapid gelation and strong tissue adhesion properties through photopolymerization. Moreover, the high substitution of catechol groups with unoxidized state can not only induce red blood cell aggregation and platelets adhesion but also adhere to wound tissue to further enhance hemostasis. Based on its bio-adhesion and procoagulant activity, the DMHA hydrogel formed in situ reveals superior hemostatic performance in the rat liver injury model and noncompressible hemorrhage model, and rabbit femoral artery puncture model, compared to commercial products (gauze, absorbable gelatin sponge) and oxidized DMHA (SMHA) hydrogel. Besides, the hydrogel exhibited good adaptability, biodegradability, and superior cytocompatibility as well as negligible inflammation. This hydrogel adhesive is a promising biological adhesive for hemorrhage control.

Euryale ferox stem-inspired anisotropic quaternized cellulose/xanthan-based antibacterial sponge with high absorbency and compressibility for noncompressible hemorrhage

Uncontrollable hemorrhage from deep noncompressible wounds remains an intractable challenge. Herein, inspired by the euryale ferox stem which is capable of transporting water and nutrient substances efficiently along longitudinally aligned channels, an anisotropic sponge with rapidly liquid absorption capacity, excellent mechanical compressibility and antibacterial property based on quaternized cellulose (QC), xanthan gum (XG) and reduced graphene oxide (rGO), was constructed. The euryale ferox stem-like structure and multiple interactions, involving hydrogen bonding, electrostatic interaction and chemical crosslinking, endowed the sponge with excellent fatigue resistance, elasticity and efficient liquid absorption capacity. In vivo rat liver injury, tail amputation and liver noncompressible hemorrhage model experiments confirmed that the sponge exhibited superior hemostatic performance than commercial gelatin sponge, attributing to the positive charge, efficient absorption capacity and rough surface of the sponge, which synergistically promoting the aggregation and activation of red blood cells and platelets as well as formation of fibrin network, leading to accelerated blood coagulation process. Besides, the sponge showed favorable cytocompatibility, hemocompatibility and antibacterial property. Overall, the bioinspired sponge had fantastic potential for controlling deep noncompressible hemorrhage and providing a new idea for designing hemostatic materials.

Gelatin Methacryloyl-Based Sponge with Designed Conical Microchannels for Rapidly Controlling Hemorrhage and Theoretical Verification.

It remains a challenge to develop effective hemostatic products in battlefield rescue for noncompressible massive hemorrhage. Some previous research had concentrated on the modification of different materials to improve the hemostasis ability of sponges. Herein, to investigate the relationship between the taper of microchannels and hemostatic performance of porous sponges, gelatin methacryloyl-based sponges with designed conical microchannels and a disordered porous structure were prepared using the 3D printing method and freeze-drying technology. Experiments and theoretical model analysis demonstrated that the taper and distribution of microchannels in the sponge affected the water and blood absorption properties, as well as the expansion ability. In treatment of SD rat liver defect and SD rat liver perforation wound, GS-1 sponge with the taper (1/15) microchannels exhibited an excellent hemostatic effect with blood loss of 0.866 ± 0.093 g and a hemostasis time of 280 ± 10 s. Results showed that the hemostatic capacities of GelMA sponges were increased with the bottom diameter (taper) of conical microchannels. This is a potential strategy to develop designed taper sponges with designed taper microchannels for rapidly controlling hemorrhage.

Polysaccharides based rapid self-crosslinking and wet tissue adhesive hemostatic powders for effective hemostasis

Hemostatic powders with flexible shape are widely used for the noncompressible and inaccessible hemorrhage wounds. However, current hemostatic powders display poor wet tissue adhesion and fragile mechanical strength of the powder-supported blood clots, leading to compromised hemostasis efficacy. Herein, a bi-component of carboxymethyl chitosan (CMCS) and aldehyde-modified hyaluronic acid grafted with catechol groups (COHA) was designed. Upon absorption of blood, the bi-component powders (CMCS-COHA) spontaneously self-crosslinks into an adhesive hydrogel within 10 s, tightly adhering to wound tissue to form a pressure-resistant physical barrier. During gelation, the hydrogel matrix captures and locks the blood cells/platelets to generate a robust thrombus in the bleeding sites. Compared with traditional hemostatic powder Celox™, CMCS-COHA displays superior blood coagulation and hemostatic performance. More importantly, CMCS-COHA has inherent cytocompatibility and hemocompatibility. These prominent advantages in rapid and effective hemostasis, adaptability to fit irregulate defective wound, easy preservation, facile usage, and bio-safety, make CMCS-COHA a promising hemostatic in emergency situations.

An anticoagulant/procoagulant self-converting and bleeding site–targeting systemic nanotherapy for rapidly controlling noncompressible bleeding without risk of thrombosis

BackgroundHemorrhage, in particular noncompressible hemorrhage, is the leading cause of casualties in combat trauma and civilian trauma. Although systemic agents can stop bleeding at both inaccessible and accessible injury sites, the application of systemic hemostats in clinics is strictly limited by the nontargeting ability of hemostats and their subsequent potential for thromboembolic complications. ObjectivesTo engineer an anticoagulant/procoagulant self-converting and bleeding site–targeting systemic nanohemostat to rapidly control noncompressible bleeding without thrombosis risk. MethodsA multiscale computer simulation was taken to guide the self-assembly of sulindac (SUL, a prodrug of the antiplatelets agent) and poly-L-lysine (a cation polymer with platelets activation ability) for forming poly-L-lysine/SUL nanoparticles (PSNs). In vitro platelet-adhering ability, platelet activation effect, and hemostasis activity of PSNs were evaluated. Then, the biosafety, level of thrombosis, targeting ability, and hemostasis effect of systemic applied PSNs were carefully evaluated in various hemorrhage models. ResultsPSNs were successfully prepared and showed good platelet adhesion and activation in vitro. The bleeding site–targeting ability and hemostatic efficiency in different bleeding models were leveled up by PSNs markedly compared with vitamin K and etamsylate in vivo. SUL in PSNs could be metabolized into sulindac sulfide at clot sites in 4 hours for antiplatelet aggregation, thus reducing thrombotic risk compared with other hemostatic agents, via the ingenious utilization of prodrug metabolism in terms of time intervals and the adhesion on platelets. ConclusionPSNs are expected to be a low-cost, safe, efficient, clinically translatable first-aid hemostat for first-aid scenarios.

Succinic Ester‐Based Shape Memory Gelatin Sponge for Noncompressible Hemorrhage without Hindering Tissue Regeneration (Adv. Healthcare Mater. 5/2023)

Shape Memory Sponges In article 2202122, Xifu Zheng, Yazhong Bu, and co-workers successfully develop a fast degradable shape memory sponge for noncompressible hemorrhage without hindering tissue regeneration. The resulting sponge possesses high mechanical stability and hemostatic efficiency. Meanwhile, its fast degradation, resulting from succinic esters, leads to fast tissue regeneration when compared with a commercialized sponge. This sponge is composed of components with well-identified biocompatibility, making it very promising in the clinic.

Janus Self‐Propelled Chitosan‐Based Hydrogel Spheres for Rapid Bleeding Control

Uncontrolled hemorrhage is a major cause of potentially preventable death in civilian trauma nowadays. Considerable concern has been given to the development of efficient hemostats with high blood absorption, self-propelled property, and Ca2+ release ability, for irregularly shaped and noncompressible hemorrhage. Herein, Janus self-propelled chitosan-based hydrogel with CaCO3 (J-CMH@CaCO3 ) is developed by partial ionic crosslinking of carboxylated chitosan (CCS) and Ca2+ , gravity settlement, and photopolymerization, followed by removing the shell of CCS. The obtained J-CMH@CaCO3 is further used as a hemostat powered by the internal CaCO3 and coordinated protonated tranexamic acid (J-CMH@CaCO3 /T). Bubbles are generated and detached to provide the driving force, accompanied by the release of Ca2+ . The two aspects work in synergy to accelerate clot formation, endowing the J-CMH@CaCO3 /T with excellent hemostatic efficiency. The J-CMH@CaCO3 /T presents high blood absorption, favorable blood-clotting ability, desired erythrocyte and platelet aggregation, and acceptable hemocompatibility and cytocompatibility. In rodentand rabbitbleeding models, the J-CMH@CaCO3 /T exhibits the most effective hemostasis to the best knowledge of the authors, wherein the hemorrhage is rapidly halted within 39 s. It is believed that the J-CMH@CaCO3 /T with self-propelled property opens up a new avenue to design high-performance hemostats for clinical application.

An Antibacterial and Antiadhesion In Situ Forming Hydrogel with Sol–Spray System for Noncompressible Hemostasis

Noncompressible hemorrhage is a major cause of posttrauma death and occupies the leading position among potentially preventable trauma-associated deaths. Recently, multiple studies have shown that strongly adhesive materials can serve as hemostatic materials for noncompressible hemorrhage. However, the risk of severe tissue adhesion limits the use of adhesive hydrogels as hemostatic materials. Here, we report a promising material system comprising an injectable sol and liquid spray as a potential solution. Injectable sol is mainly composed of gelatin (GEL) and sodium alginate (SA), which possess hemostasis and adhesive properties. The liquid spray component, a mixture of tannic acid (TA) and calcium chloride (CaCl2), rapidly forms an antibacterial, antiadhesive and smooth film structure upon contact with the sol. In vitro and in vivo experiments demonstrated the bioabsorbable, biocompatible, antibacterial, and antiadhesion properties of the in situ forming hydrogel with a sol-spray system. Importantly, the addition of tranexamic acid (TXA) enhanced hemostatic performance in noncompressible areas and in deep wound hemorrhage. Our study offers a new multifunctional hydrogel system to achieve noncompressible hemostasis.

Severe trauma patients requiring undelayable combined cranial and extracranial surgery: A scoping review of an emerging concept.

Although patients suffering from severe traumatic brain injury (sTBI) and severe trauma patients (STP) have been extensively studied separately, there is scarce evidence concerning STP with concomitant sTBI. In particular, there are no guidelines regarding the emergency surgical management of patients presenting a concomitant life-threatening intracranial hematoma (ICH) and a life-threatening non-compressible extra-cranial hemorrhage (NCEH). A scoping review was conducted on Medline database from inception to September 2021. The review yielded 138 articles among which 10 were retained in the quantitative analysis for a total of 2086 patients. Seven hundrer and eighty-seven patients presented concomitant sTBI and extra-cranial severe injuries. The mean age was 38.2 years-old and the male to female sex ratio was 2.8/1. Regarding the patients with concomitant cranial and extra-cranial injuries, the mean ISS was 32.1, and the mean AIS per organ were 4.0 for the head, 3.3 for the thorax, 2.9 for the abdomen and 2.7 for extremity. This review highlighted the following concepts: emergency peripheric osteosynthesis can be safely performed in patients with concomitant sTBI (grade C). Invasive intracranial pressure monitoring is mandatory during extra-cranial surgery in patients with sTBI (grade C). The outcome of STP with concomitant sTBI mainly depends on the seriousness of sTBI, independently from the presence of extra-cranial injuries (grade C). After exclusion of early-hospital mortality, the impact of extra-cranial injuries on mortality in patients with concomitant sTBI is uncertain (grade C). There are no recommendations regarding the combined surgical management of patients with concomitant ICH and NCEH (grade D). This review revealed the lack of evidence for the emergency surgical management of patients with concomitant ICH and NCEH. Hence, we introduce the concept of combined cranial and extra-cranial surgery. This damage-control surgical strategy aims to reduce the time spent with intracranial hypertension and to hasten the admission in the intensive care unit. Further studies are required to validate this concept in clinical practice.

Strongly-adhesive easily-detachable carboxymethyl cellulose aerogel for noncompressible hemorrhage control

Hemostats that can strongly adhere to wound tissue and are easy to remove when stopping bleeding are favored for the control of noncompressible hemorrhage. Here, we prepared a citric acid (CA)-crosslinked and N-hydroxysuccinimide (NHS) ester-activated carboxymethyl cellulose (CMC-NHS) aerogel for noncompressible hemostasis. CA was used to crosslink CMC to form a strengthened structure. NHS ester was introduced to activate the adhesion of CMC-NHS aerogel to wound tissue and promoted blood coagulation through the formation of amide crosslinks between CMC and erythrocytes and free blood proteins. The plentiful carboxyl groups could also trigger the intrinsic coagulation pathway. Thus, the aerogel could quickly adhere to wound tissue to stop bleeding, and then could be easily removed when fully hydrated as CMC was dissolved at the adhesion interface. The aerogel also had good biocompatibility and antibacterial capability. Overall, CMC-NHS aerogel is a competitive hemostat for the control of noncompressible hemorrhage.