Thrombotic microenvironment responsive crosslinking cyclodextrin metal-organic framework nanocarriers for precise targeting and thrombolysis.

Global public health is seriously threatened by thrombotic disorders because of their high rates of mortality and disability. Most thrombolytic agents, especially protein-based pharmaceuticals, have a short half-life in circulation, reducing their effectiveness in thrombolysis. The creation of an intelligent drug delivery system that delivers medication precisely and releases it under regulated conditions at nearby thrombus sites is essential for effective thrombolysis. In this article, we present a unique medication delivery system (MCRUA) that selectively targets platelets and releases drugs by stimulation from the thrombus' microenvironment. The thrombolytic enzyme urokinase-type plasminogen-activator (uPA) and the anti-inflammatory medication Aspirin (acetylsalicylic acid, ASA) are both loaded onto pH-sensitive CaCO3/cyclodextrin crosslinking metal-organic frameworks (MC) that make up the MCRUA system. c(RGD) is functionalized on the surface of MC, which is functionalized by RGD to an esterification reaction. Additionally, the thrombus site's acidic microenvironment causes MCRUA to disintegrate to release uPA for thrombolysis and aiding in vessel recanalization. Moreover, cyclodextrin-encapsulated ASA enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy. When used for thrombotic disorders, our drug delivery system (MCRUA) promotes thrombolysis, suppresses rethrombosis, and enhances biosafety with fewer hemorrhagic side effects.

Dual-targeting fucoidan-based microvesicle for arterial thrombolysis and re-occlusion inhibition.

Arterial thrombosis is a critical thrombotic disease that poses a significant threat to human health. However, the existing clinical treatment of arterial thrombosis lacks effective targeting and precise drug release capability. In this study, we developed a system for targeted delivery and on-demand release in arterial thrombosis treatment. The carrier was constructed using chitosan (CS) and fucoidan (Fu) through layer-by-layer assembly, with subsequent surface modification using cRGD peptide. Upon encapsulation of urokinase-type plasminogen activator (uPA), the resulting therapeutic drug delivery system, uPA-CS/Fu@cRGD, demonstrated dual-targeting abilities towards P-selectin and αIIbß3, as well as pH and platelet-responsive release properties. Importantly, we have demonstrated that the dual targeting effect exhibits higher targeting efficiency at shear rates simulating thrombosed arterial conditions (1800 s-1) compared to single targeting for the first time. In the mouse common iliac artery model, uPA-CS/Fu@cRGD exhibited great thrombolytic capability while promoting the down-regulation of coagulation factors (FXa and PAI-1) and inflammatory factors (TNF-α and IL-6), thus improving the thrombus microenvironment and exerting potential in preventing re-occlusion. Our dual-target and dual-responsive, fucoidan-based macrovesicle represent a promising platform for advanced drug target delivery applications, with potential to prevent coagulation tendencies as well as improving thrombolytic and reducing the risk of re-occlusion.

Facilely Prepared Thirsty Granules Arouse Tough Wet Adhesion on Overmoist Wounds for Hemostasis and Tissue Repair.

Bioadhesives have been widely used in hemostasis and tissue repair, but the overmoist and wet nature of wound surface (due to the presence of blood and/or wound exudate) has led to poor wet adhesion of bioadhesives, which interrupts the continuous care of wounds. Here, a thirsty polyphenolic silk granule (Tan@SF-pwd-hydro), which absorbs blood and exudate to self-convert to robust bioadhesives (Tan@SF-gel-hydro) in situ, was facilely developed in this study for enhanced wet adhesion toward hemostasis and tissue repair. Tan@SF-pwd-hydro could shield wounds' wetness and immediately convert itself to Tan@SF-gel-hydro to seal wounds for hemorrhage control and wound healing. The maximum adhesiveness of Tan@SF-gel-hydro over wet pigskin was as high as 59.8 ± 2.1 kPa. Tan@SF-pwd-hydro is a promising transformative dressing for hemostasis and tissue repair since its hemostatic time was approximately half of that of the commercial hemostatic product, CeloxTM, and its healing period was much shorter than that of the commercial bioadhesive product, TegadermTM. This pioneering study utilized adverse wetness over wounds to arouse robust adhesiveness by converting thirsty granules to bioadhesives in situ, creatively turning adversity into opportunities. The facile fabrication approach also offers new perspectives for manufacturing sustainability of biomaterials.

A sandwich-like silk fibroin/polysaccharide composite dressing with continual biofluid draining for wound exudate management.

Optimal wound healing requires a wet microenvironment without over-hydration. Inspired by capillarity and transpiration, we have developed a sandwich-like fibers/sponge dressing with continuous exudate drainage to maintain appropriate wound moisture. This dressing is prepared by integrating a three-layer structure using the freeze-drying method. Layer I, as the side that contacts with the skin directly, consists of a hydrophobic silk fibroin membrane; Layer II, providing the pumping action, is made of superabsorbent chitosan-konjac glucomannan sponge; Layer III, accelerating evaporation sixfold compared to natural evaporation, is constructed with a graphene oxide soaked hydrophilic cellulose acetate membrane. Animal experiments showed that the composite dressing had superior wound-healing characteristics, with wounds decreasing to 24.8% of their original size compared to 28.5% for the commercial dressing and 43.2% for the control. The enhanced wound healing can be ascribed to the hierarchical porous structure serves as the fluid-driving factor in this effort; the hydrophilicity of a membrane composed of silk fibroin nanofibers is adjustable to regulate fluid-transporting capacity; and the photothermal effect of graphene oxide guarantees exudates that have migrated to the top layer to evaporate continuously. These findings indicate the unidirectional wicking dressing has the potential to become the next generation of clinical dressings.

Chitosan/silk fibroin nanofibers-based hierarchical sponges accelerate infected diabetic wound healing via a HClO self-producing cascade catalytic reaction.

The diabetic chronic wound healing is extremely restricted by issues such as hyperglycemia, excessive exudate and reactive oxygen species (ROS), and bacterial infection, causing significant disability and fatality rate. Herein, the chitosan/silk fibroin nanofibers-based hierarchical 3D sponge (CSSF-P/AuGCs) with effective exudate transfer and wound microenvironment modulation are produced by integrating cascade reactor (AuGC) into sponge substrates with parallel-arranged microchannels. When applied to diabetic wounds, the uniformly parallel-arranged microchannels endow CSSF-P/AuGCs with exceptional exudate absorption capacity, keeping the wound clean and moist; additionally, AuGCs efficiently depletes glucose in wounds to generate H2O2, which is then converted into HClO via cascade catalytic reaction to eliminate bacterial infection and reduce inflammation. Experiments in vitro demonstrated that the antibacterial activity of CSSF-P/AuGCs against S. aureus and E. coli was 92.7 and 94.27 %, respectively. Experiments on animals indicated that CSSF-P/AuGC could cure wounds in 11 days, displaying superior wound-healing abilities when compared to the commercial medication Tegaderm™. This versatile CSSF-P/AuGCs dressing may be an attractive choice for expediting diabetic wound healing with little cytotoxicity, providing a novel therapeutic method for establishing a favorable pathological microenvironment for tissue repair.

In situ generation of bioadhesives using dry tannic silk particles: a wet-adhesion strategy relying on removal of hydraulic layer over wet tissues for wound care.

Tissue adhesives have been widely used in biomedical applications. However, the presence of a hydrated layer on the surface of wet tissue severely hinders their adhesion capacities, resulting in ineffective wound treatment. To address this issue, a dry particle dressing (plas@SF/tann-hydro-pwd) capable of removing the hydrated layer and converting in situ to bioadhesives (plas@SF/tann-hydro-gel) was fabricated via simple physical mixing based on the hydrophobic-hydrogen bonding synergistic effect and Schiff-base reaction. It was found that the plas@SF/tann-hydro-gel bioadhesive, which was changed from plas@SF/tann-hydro-pwd dressing by adsorption of water, exhibited good wet adhesion to diverse biological tissues. In addition, the wet adhesion qualities of the plas@SF/tann-hydro-gel adhesive was studied under a variety of demanding conditions, including a wide range of temperatures, varying pH levels, highly concentrated salt solutions, and simulated fluids. Experiments on animals had showed that the adhesive plas@SF/tann-hydro-gel has superior wet adhesion qualities and superior wound healing properties compared to the commercial product Tegaderm™. This study develops a new wet-adhesion technique employing dry particle dressing to eliminate the hydrated layer over wet tissues for the in situ creation of gel bioadhesives for wound healing.

Catechol-chitosan/carboxymethylated cotton-based Janus hemostatic patch for rapid hemostasis in coagulopathy.

Uncontrolled bleeding is the leading cause of death, and the death risk of bleeding from coagulopathy is even higher. By infusing the relevant coagulation factors, bleeding in patients with coagulopathy can be clinically treated. However, there are not many emergency hemostatic products accessible for coagulopathy patients. In response, a Janus hemostatic patch (PCMC/CCS) with a two-layer structure of partly carboxymethylated cotton (PCMC) and catechol-grafted chitosan (CCS) was developed. Ultra-high blood absorption (4000 %) and excellent tissue adhesion (60 kPa) were both displayed by PCMC/CCS. The proteomic analysis revealed that PCMC/CCS has significantly contributed to the creative generation of FV, FIX, and FX, as well as to the substantial enrichment of FVII and FXIII, re-paving the initially blocked coagulation pathway of coagulopathy to promote hemostasis. The in vivo bleeding model of coagulopathy demonstrated that PCMC/CCS was substantially more effective than gauze and commercial gelatin sponge at achieving hemostasis in just 1 min. The study provides one of the first investigations on procoagulant mechanisms in anticoagulant blood conditions. Rapid hemostasis in coagulopathy will be significantly affected by the results of this experiment.

Bioinspired Hemostatic Strategy via Pulse Ejections for Severe Bleeding Wounds.

Efficient hemostasis during emergency trauma with massive bleeding remains a critical challenge in prehospital settings. Thus, multiple hemostatic strategies are critical for treating large bleeding wounds. In this study, inspired by bombardier beetles to eject toxic spray for defense, a shape-memory aerogel with an aligned microchannel structure was proposed, employing thrombin-carrying microparticles loaded as a built-in engine to generate pulse ejections for enhanced drug permeation. Bioinspired aerogels, after contact with blood, can rapidly expand inside the wound, offering robust physical barrier blocking, sealing the bleeding wound, and generating a spontaneous local chemical reaction causing an explosive-like generation of CO2 microbubbles, which provide propulsion thrust to accelerate burst ejection from arrays of microchannels for deeper and faster drug diffusion. The ejection behavior, drug release kinetics, and permeation capacity were evaluated using a theoretical model and experimentally demonstrated. This novel aerogel showed remarkable hemostatic performance in severely bleeding wounds in a swine model and demonstrated good degradability and biocompatibility, displaying great potential for clinical application in humans.

Dual modes reinforced silk adhesives for tissue repair: Integration of textiles and inorganic particles in silk gel for enhanced mechanical and adhesive strength.

Skin wound healing in dynamic environments remains challenging. Conventional gels are not ideal dressing materials for wound healing due to difficulties in completely sealing wounds and the inability to deliver drugs quickly and precisely to the injury. To tackle these issues, we propose a multifunctional silk gel that rapidly forms strong adhesions to tissue, has excellent mechanical properties, and delivers growth factors to the wound. Specifically, the presence of Ca2+ in the silk protein leads to a solid adhesion to the wet tissue through a chelation reaction with water-trapping behavior; the integrated chitosan fabric and CaCO3 particles ensure enhanced mechanical strength of the silk gel for better adhesion and robustness during wound repair; and the preloaded growth factor further promoted wound healing. The results showed the adhesion and tensile breaking strength were as high as 93.79 kPa and 47.20 kPa, respectively. MSCCA@CaCO3-aFGF could remedy the wound model in 13 days, with 99.41 % wound shrinkage without severe inflammatory responses. Due to strong adhesion properties and mechanical strength, MSCCA@CaCO3-aFGF can be a promising alternative to conventional sutures and tissue closure staples for wound closure and healing. Therefore, MSCCA@CaCO3-aFGF is expected to be a strong candidate for the next generation of adhesives.

Gas-jet propelled hemostats for targeted hemostasis in wounds with irregular shape and incompressibility.

Since hemostats are likely to be flushed off a wound by a massive gushing of blood, achieving rapid and effective hemostasis in complex bleeding wounds with powder hemostats continues to be a significant therapeutic challenge. In order to counter the flushing effect of gushing blood, a gas-jet propelled powder hemostat ((COL/PS)4@CaCO3-T-TXA+) has been developed. (COL/PS)4@CaCO3-T-TXA+ dives into the deep bleeding sites of complex wounds for targeted hemostasis. In preparation, protamine sulfate and collagen are first electrostatically deposited on CaCO3, which is then loaded with thrombin, and finally doped with protonated tranexamic acid (TXA-NH3+) to produce the final therapeutic medicine (COL/PS)4@CaCO3-T-TXA+. When applied to bleeding tissues, CaCO3 and TXA-NH3+ from (COL/PS)4@CaCO3-T-TXA+ immediately react with each other in blood to release countless CO2 macro-bubbles, which direct the hemostatic powder, (COL/PS)4@CaCO3-T-TXA+, precisely towards deep bleeding sites from complex wounds. Then the carried thrombin is released to accomplish targeted hemostasis. According to animal studies, (COL/PS)4@CaCO3-T-TXA+ has better effects in rabbit hepatic hemorrhage models; the hemorrhage quickly stops within 30 s, which is roughly 20% less than with the commercial product CeloxTM. The present study provides a new strategy for using powder hemostats to quickly and effectively stop bleeding in complex bleeding wounds.

Dual-Driven Hemostats Featured with Puncturing Erythrocytes for Severe Bleeding in Complex Wounds.

Achieving rapid hemostasis in complex and deep wounds with secluded hemorrhagic sites is still a challenge because of the difficulty in delivering hemostats to these sites. In this study, a Janus particle, SEC-Fe@CaT with dual-driven forces, bubble-driving, and magnetic field- (MF-) mediated driving, was prepared via in situ loading of Fe3O4 on a sunflower sporopollenin exine capsule (SEC), and followed by growth of flower-shaped CaCO3 clusters. The bubble-driving forces enabled SEC-Fe@CaT to self-diffuse in the blood to eliminate agglomeration, and the MF-mediated driving force facilitated the SEC-Fe@CaT countercurrent against blood to access deep bleeding sites in the wounds. During the movement in blood flow, the meteor hammer-like SEC from SEC-Fe@CaT can puncture red blood cells (RBCs) to release procoagulants, thus promoting activation of platelet and rapid hemostasis. Animal tests suggested that SEC-Fe@CaT stopped bleeding in as short as 30 and 45 s in femoral artery and liver hemorrhage models, respectively. In contrast, the similar commercial product Celox™ required approximately 70 s to stop the bleeding in both bleeding modes. This study demonstrates a new hemostat platform for rapid hemostasis in deep and complex wounds. It was the first attempt integrating geometric structure of sunflower pollen with dual-driven movement in hemostasis.

Microcluster colloidosomes for hemostat delivery into complex wounds: A platform inspired by the attack action of torpedoes.

Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature, thereby causing massive blood loss and significantly increased mortality. Inspired by the attack action of torpedoes, we synthesized microcluster (MC) colloidosomes equipped with magnetic-mediated navigation and "blast" systems to deliver hemostats into the cavity of vase-type wounds. CaCO3/Fe2O3 (CF) microparticles functionalized with Arg-Gly-Asp (RGD) modified polyelectrolyte multilayers were co-assembled with oppositely charged zwitterionic carbon dots (CDs) to form MC colloidosomes, which were loaded with thrombin and protonated tranexamic acid (TXA-NH3 +). The composite microparticles moved against blood flow under magnetic mediation and simultaneously disassembled for the burst release of thrombin stimulated by TXA-NH3 +. The CO2 bubbles generated during disassembly produced a "blast" that propelled thrombin into the wound cavity. Severe bleeding in a vase-type hemorrhage model in the rabbit liver was rapidly controlled within ∼60 s. Furthermore, in vivo subcutaneous muscle and liver implantation models demonstrated excellent biodegradability of MC colloidosomes. This study is the first to propose a novel strategy based on the principle of torpedoes for transporting hemostats into vase-type wounds to achieve rapid hemostasis, creating a new paradigm for combating trauma treatment.

Recent advances in materials for hemostatic management.

Traumatic hemorrhage can be a fatal event, particularly when large quantities of blood are lost in a short period of time. Therefore, hemostasis has become a crucial part of emergency treatment. For small wounds, hemostasis can be achieved intrinsically depending on the body's own blood coagulation mechanism; however, for large-area wounds, particularly battlefield and complex wounds, materials delivering rapid and effective hemostasis are required. In parallel with the constant progress in science, technology, and society, advances in hemostatic materials have also undergone various iterations by integrating new ideas with old concepts. There are various natural and synthetic hemostatic materials, including hemostatic powders, adhesives, hydrogels, and tourniquets, for the treatment of severe external trauma. This review covers the differences among the currently available hemostatic materials and comprehensively describes the hemostatic effects of different materials based on the underlying mechanisms. Finally, solutions for current issues related to trauma bleeding are discussed, and the prospects of hemostatic materials are proposed.

Magnetic field-mediated Janus particles with sustained driving capability for severe bleeding control in perforating and inflected wounds.

Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge. Therefore, we present a novel hemostatic strategy based on magnetic field-mediated guidance. The biphasic Janus magnetic particle (MSS@Fe2O3-T) comprised aggregates of α-Fe2O3 nanoparticles (Fe2O3 NPs) as the motion actuator, negatively modified microporous starch (MSS) as the base hemostatic substrate, and thrombin as the loaded hemostatic drug. Before application, the particles were first wrapped using NaHCO3 and then doped with protonated tranexamic acid (TXA-NH3 +), which ensured their high self-dispersibility in liquids. During application, the particles promptly self-diffused in blood by bubble propulsion and travelled to deep bleeding sites against reverse rushing blood flow under magnetic guidance. In vivo tests confirmed the superior hemostatic performance of the particles in perforating and inflected wounds ("V"-shaped femoral artery and "J"-shaped liver bleeding models). The present strategy, for the first time, extends the range of magnetically guided drug carriers to address the challenges in the hemorrhage control of perforating and inflected wounds.

Magnetically Guided Nanoworms for Precise Delivery to Enhance In Situ Production of Nitric Oxide to Combat Focal Bacterial Infection In Vivo.

Overexploitation of antibiotics increases the emergence of multidrug-resistant agents (MDRAs), which may potentially cause a global crisis with severe health consequences. Hence, there is great demand for next-generation antibacterial platforms based on antibiotic-free strategies or targeted therapies to mitigate the emergence of MDRAs. Herein, an all-in-one hollow nanoworm (A-Fe/AuAg@PDA) is developed with a core comprising citrate-capped Au-Ag nanoparticles (Cit-AuAg NPs) loaded with Fe2O3 and an l-arginine (L-Arg)-modified polydopamine (PDA) outer shell, possessing exceptional magnetic-targeting ability and a photothermal therapeutic effect. Following intravenous injection, A-Fe/AuAg@PDA can be precisely delivered to the targeted infection sites by an externally applied magnetic field. The in situ produced NO, together with Ag ions and reactive oxygen species, synergistically results in the highly effective elimination of in vivo bacterial infection. With the aid of functional worm-like A-Fe/AuAg@PDA nanocarriers possessing superior biocompatibility, the combination of magnetic guidance therapy and near-infrared-triggered in situ generation of NO may provide a novel approach for eradicating abscesses in the body. To our knowledge, this is the first study highlighting the magnetically guided delivery of worm-like nanocarriers for the antibiotic-free therapy of bacterial infections using in situ generated NO gas, which demonstrates high potential for application in clinical gas therapy.

Chestnut-like macro-acanthosphere triggered hemostasis: a featured mechanism based on puncturing red blood cells.

Acute hemorrhage that occurs after trauma is a life-threatening condition. Hence, to halt massive bleeding, there is a critical need to develop a suitable therapy. In this study, we developed self-propelling chestnut-like particles (Pro-MAS) comprising a macro-acanthosphere (MAS) coated with calcium carbonate and protonated tranexamic acid to puncture red blood cells (RBCs) and thus activate hemostasis. In vitro assessments revealed that Pro-MAS was biocompatible, biodegradable, and nontoxic; furthermore, it was capable of puncturing RBCs to release procoagulants and activate platelet aggregation for hemostasis. Animal tests showed that self-propelling Pro-MAS effectively traveled through blood flow to the deep ends of wounds; hemorrhage was controlled within 90 s and 4 min in the injured liver and bleeding femoral artery, respectively. Compared with a commercial hemostat, superior hemostasis was achieved with Pro-MAS, which could be ascribed to its functional and structural features. Overall, traveling Pro-MAS possessed sufficient impact force to puncture RBCs and sufficient momentum to reach the targeted bleeding sites. The present study demonstrated the ability of a novel platform, self-propelling MAS particles, to trigger hemostasis by puncturing RBCs. To the best of our knowledge, this is the first trial in which the release of endogenous procoagulants is promoted without the addition of exogenous procoagulants for severe hemorrhage control.

Biogenetic Acellular Dermal Matrix Maintaining Rich Interconnected Microchannels for Accelerated Tissue Amendment.

Given that many people suffer from extensive skin damage, wound repair has drawn tremendous attention in research. Among the various assistant dressing materials that promote healing, a porcine acellular dermal matrix (PADM), as a skin substitute, can efficiently accelerate healing by promoting cell migration and proliferation. However, a simple, low-cost preparation process remains a challenge facing PADM development, particularly because of the inferior elasticity. To overcome these drawbacks, a CaCl2-ethanol-H2O solution (ternary solution) combined with an additional enzyme treatment was used to obtain a transparent, porous, and elastic PADM that retained the major extracellular matrix composition of the dermis. Our results indicated that alterations in the fiber organization and secondary structural changes in the collagen occurred after treatment. Furthermore, the in vivo wound healing and histological analyses clearly revealed an extremely expedited wound repair process following the application of the biocompatible PADM. In conclusion, this study provides new insights into the development of a transparent PADM with a porous structure and good elasticity that can be used as a skin substitute to accelerate the wound healing process. Moreover, this effective technique could potentially be used to extrapolate other decellularized materials in the future.

Erythrocyte membrane-camouflaged nanoworms with on-demand antibiotic release for eradicating biofilms using near-infrared irradiation.

The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics. Bacterial infections are detrimental to our life and health. To reduce the abuse of antibiotics and treat biofilm-related bacterial infections, a biomimetic nano-antibacterial system, RBCM-NW-G namely, that controls the release of antibiotics through near infrared was prepared. The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading, and then, biomimetics are applied with red blood cell membranes (RBCM). RBCM-NW-G, which retains the performance of RBCM, shows enhanced permeability and retention effects. Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection. In addition, the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility. Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect, silver iron, and antibiotics. Finally, by constructing a mouse infection model, the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.

A self-adapting hydrogel based on chitosan/oxidized konjac glucomannan/AgNPs for repairing irregular wounds.

Wound dressings play a critical role in the cutaneous healing process. The uncertainty of an injury leads to an irregular wound. However, incomplete contact between a general dressing and wound reduces the effectiveness of the dressing. Therefore, self-adapting hydrogels that are adhesive, injectable, and self-healable are being developed to efficiently treat irregular skin wounds. Here, we present an approach based on dynamic Schiff-base bond formation to prepare self-adapting hydrogel dressings that automatically adapt to irregular wounds under natural conditions and sustain total contact with the injured site. Spectroscopic investigations suggested the formation of dynamic covalent Schiff-base bonds, which are closely associated with the rapid formation of the hydrogel, between the aldehyde groups of oxidized konjac glucomannan and amine groups in the backbone of protonated chitosan and protonated tranexamic acid. Rheological analysis confirmed the self-healing property of the hydrogel, that is, the recovery of the broken hydrogel network. Histological analysis indicated that this self-adapting hydrogel provides a clear advantage over the commercial hydrogel dressing (AquacelAg™) in the in vivo wound-healing process. Our rapidly gelating hydrogel formulations with self-healing ability, tissue adhesiveness, and antibacterial activity are very promising self-adapting biomaterials for repairing irregular wounds.

Puff pastry-like chitosan/konjac glucomannan matrix with thrombin-occupied microporous starch particles as a composite for hemostasis.

Hemorrhage control is key for reducing mortality following severe trauma. In this study, we produced a puff pastry-like chitosan/konjac glucomannan matrix loaded with thrombin-occupied microporous starch particles to initiate hemostasis. The composite showed a hierarchical porous structure system consisting of porous and rough structures with evenly distributed microporous starch particles. Thrombin was evenly and independently distributed on the microporous starch particles within the hierarchical system and served to accelerate hemostasis. Meanwhile, the composite displayed excellent water absorption capacity, high zeta potential, roughness, and porosity. The composite was found to elicit desirable pro-thrombin time (PT), activated partial thrombin time (APTT), and whole blood clotting indices (BCI). Experiments using animal models demonstrated that the composite could effectively control wound hemorrhage. Furthermore, the composite showed good biocompatibility and effective degradability. Together, our results show that the puff pastry-like hemostat with hierarchical porous structure offers significant potential for use in hemostasis control.