Rapid Hemostasis Research Articles

A novel macroporous carboxymethyl chitosan/sodium alginate sponge dressing capable of rapid hemostasis and drug delivery

Carboxymethyl chitosan (CMCS) and sodium alginate (SA), which are excellent polysaccharide-based hemostatic agents, are capable of forming polyelectrolyte complexes (PEC) through electrostatic interactions. However, CMCS/SA PEC sponges prepared by the conventional sol-gel process exhibited slow liquid absorption rate and poor mechanical properties post-swelling. In this work, a novel strategy involving freeze casting followed by acetic acid vapor treatment to induce electrostatic interactions was developed to fabricate novel PEC sponges with varying CMCS/SA mass ratios. Compared to sol-gel process sponge, the novel sponge exhibited a higher density of electrostatic interactions, resulting in denser pore walls that resist re-gelation and swelling according to FTIR, XRD, and SEM analyses. Additionally, the liquid absorption kinetics, as well as compression and tension tests, demonstrated that the novel sponge had significantly improved rapid blood absorption capacity and mechanical properties. Furthermore, in vitro coagulation and drug release studies showed that the novel sponge had a lower blood clotting index and clotting time, along with a slower drug release rate after loading with berberine hydrochloride, showcasing its potential as a rapid hemostatic dressing with controlled drug release capabilities.

Sprayable biomimetic double mask with rapid autophasing and hierarchical programming for scarless wound healing.

Current sprayable hydrogel masks lack the stepwise protection, cleansing, and nourishment of extensive wounds, leading to delayed healing with scarring. Here, we develop a sprayable biomimetic double wound mask (BDM) with rapid autophasing and hierarchical programming for scarless wound healing. The BDMs comprise hydrophobic poly (lactide-co-propylene glycol-co-lactide) dimethacrylate (PLD) as top layer and hydrophilic gelatin methacrylate (GelMA) hydrogel as bottom layer, enabling swift autophasing into bilayered structure. After photocrosslinking, BDMs rapidly solidify with strong interfacial bonding, robust tissue adhesion, and excellent joint adaptiveness. Upon implementation, the bottom GelMA layer could immediately release calcium ion for rapid hemostasis, while the top PLD layer could maintain a moist, breathable, and sterile environment. These traits synergistically suppress the inflammatory tumor necrosis factor-α pathway while coordinating the cyclic guanosine monophosphate/protein kinase G-Wnt/calcium ion signaling pathways to nourish angiogenesis. Collectively, our BDMs with self-regulated construction of bilayered structure could hierarchically program the healing progression with transformative potential for scarless wound healing.

Recyclable thermo-responsive elastin-based adhesives with tough underwater adhesion and rapid hemostasis ability

Protein-based underwater adhesives have attracted tremendous attention due to their excellent biocompatibility compared to adhesives prepared with synthetic polymers. However, the fabrication of protein-based adhesives always requires multiple successive steps, and their underwater adhesion is quite limited. Inspired by the human elastic fibers, bone matrix, and marine adhesive proteins, a thermo-responsive underwater adhesive was fabricated through a facial one-step complexation of elastin (ELN), hydroxyapatite (HAP), and tannic acid (TA) based on multiple non-covalent molecular interactions. During underwater adhesion, the adhesive can perform sufficient flowability to adhere seamlessly and strongly to the substrates upon heating at 37 ℃ and then significantly increase its cohesion through cooling down to 25 ℃ to sustain adhesion. The regulation of the balance between adhesion and cohesion in response to temperature change enables the adhesive to exhibit a robust underwater adhesion ranging from 0.3 to 1.1 MPa to the substrates with low, medium, or high surface energy, outperforming most protein-based adhesives. Importantly, the adhesive can be further processed into powders with well-maintained underwater adhesion by a simple drying and grinding method, facilitating adhesion onto irregular-shaped target sites, reusability, and closed-loop recycling. The adhesive powder also possesses a rapid in vivo hemostatic property, suggesting a potential biomedical application.

Oxygen-Propelled Dual-Modular Microneedles with Dopamine-Enhanced RNA Delivery for Regulating Each Stage of Diabetic Wounds.

Diabetic wounds are characterized by the disruption and cessation of essential healing stages, which include hemostasis, inflammation, proliferation, and remodeling. However, traditional treatments for diabetic wounds concentrate on individual stages of the healing process. Herein, this study utilizes mask-mediated sequential polymerization and varied cross-linking techniques to develop dual-modular microneedles (MNs) with fast- and slow-module, exhibiting varying degradation rates tailored for the full spectrum of diabetic wound healing. First, MNs incorporating calcium ions and dopamine synergistically promote rapid hemostasis. Second, fast-module physically cross-linked MNs rapidly D-mannose/dopamine-enhanced tripolyphosphate-quaternized chitosan (mDTC) nanoparticles (NPs) loaded with microRNA-147 (miRNA-147) to manage inflammation and oxidative stress in diabetic wounds. Additionally, dopamine in these NPs enhances their internalization and safeguards miRNA-147 from oxidative stress and RNase degradation. Finally, slow-module chemically cross-linked MNs facilitate the continuous release of deferoxamine (DFO) and dopamine, accelerating angiogenesis and tissue regeneration during the proliferation and remodeling stages. Manganese/dopamine-enhanced calcium peroxide NPs within the MNs initiate a blast-like generation of oxygen bubbles, not only enhancing the delivery of miRNA-mDTC NPs and DFO but also alleviating tissue hypoxia. Consequently, dual-modular MNs are instrumental in promoting rapid and complete healing of diabetic wounds through all stages of healing.

Alginate Cryogels for Rapid Hemostasis and Toluidine Blue-Mediated Photodynamic Inactivation of Bacteria.

The development of new wound dressings with fast hemostatic and bactericidal properties for prehospital care is critical. Antibacterial photodynamic therapy (aPDT) has attracted attention due to its broad-spectrum antibacterial activity and minimal bacterial resistance. However, photosensitizers used in aPDT often face issues such as poor water solubility, short-lived singlet oxygen (1O2), and limited 1O2 diffusion range. In this study, sodium alginate was covalently modified with the photosensitizer toluidine blue O (TBO) and phenylboronic acid (PBA). The modified alginate was then cross-linked with Ca(II) ions and lyophilized to form a cryogel, named SA@Ca(II)@TBO@PBA (SCTP). This cryogel functions as an antibacterial photodynamic wound dressing. The chemical immobilization of TBO and PBA enhanced the cryogel's targeting ability. PBA formed reversible covalent bonds with diol groups on bacterial cell surfaces, allowing the cryogel to capture bacteria effectively and enhance aPDT. The bactericidal efficiency of the cryogel was tested through in vitro antibacterial assays, and its hemostatic properties were confirmed in vivo. The results indicate that this cryogel has excellent hemostatic and antibacterial capabilities, showing great promise as a wound dressing for clinical applications.

Cellulose nonwoven fabric coated with a chitosan/hyaluronic acid composite membrane for rapid arterial hemostasis

In scenarios of arterial bleeding, common hemostatic agents or dressings often fail due to the loss of active components, high blood loss, and high bleeding pressure. To overcome these challenges, we have developed a novel bio-based hemostatic membrane capable of rapid hemostasis under high pressure. A biomass hemostatic membrane with rapid hemostatic function under high pressure was prepared based on polyelectrolyte electrostatic self-assembly and a “concrete reinforcement” strategy. Hyaluronic acid (HA) was sprayed by airflow to form CSH hydrogel bubbles in the Chitosan (CS) solution. Then CSH hydrogel bubbles were deposited onto cellulose nonwoven (CN) by vacuum filtration, and the CSH composite membrane was obtained after drying. The hemostatic effect of several CSH composite membrane was evaluated in the analysis of venous bleeding in vitro (1.5 KPa). Among them, CS1HA0.4@CN had a small amount of blood loss, but the amount of blood loss was only about 0.29 g, the other samples did not show any blood loss. In vitro arterial bleeding analysis, CS1HA0.2@CN showed significant hemostasis in just 20 s and successfully stabilized the blood flow at 0.002 mL/s within 40 s. Despite being subjected to a high pressure of 96.235 KPa, the CSH composite membrane effectively maintains its hemostatic capability. Consequently, it is viewed as a promising solution for emergency arterial hemostasis.

Versatile Underwater Pressure Sensitive Adhesive: UV Curing Synthesis and Substrate-Independent Adhesion.

The demand for underwater pressure sensitive adhesives (PSAs) is rapidly increasing in fields such as underwater engineering and biomedicine. However, the achievement of underwater adhesion of PSAs remains a challenge because of the hydration layer that hinders the interaction between the adhesive and the substrate. Herein, a new type of underwater PSA was synthesized by the copolymerization of hydrophobic unsaturated poly(1,2-butylene oxide) (UPBO) and hydrophilic itaconic acid monomers using solvent-free ultraviolet curing. The PSA has demonstrated substrate-independent underwater adhesion strengths ranging from 108 to 141 kPa on both hydrophilic (glass, wood, steel) and hydrophobic (PET, PMMA, PTFE) substrates. The underwater adhesion performance of PSA remains stable during 30 adhesion-detachment cycles and incubation in water for 20 days. Notably, PSA shows cytocompatibility, antimicrobial, and degradable properties and can be used for rapid hemostasis of skin wounds. Experimental characterizations confirm that the process of underwater adhesion is achieved by hydrophobic alkyl side chains of the PBO chain segments, which repel water at the adhesive-substrate interface. This study should provide both practical and facile design strategies for multifunctional underwater PSAs that can be used in a variety of applications.

Advancing Bioactive Material for Mandibular Bone Regeneration: Transformation of Fibrous Mat into 3D Matrix Cotton for Enhanced Shape Retention and Rapid Hemostasis.

Transformation of a fibrous mat into a three-dimensional (3D) scaffold opens up abundant innovative prospects in biomedical research, particularly for studying both soft as well as hard tissues. Electrospun nanofibers, which mimic the extracellular matrix have attracted significant attention in various studies. This research focuses on rapidly converting a fibrous mat made of polycaprolactone (PCL)/pluronic F-127 (PF-127) with different percentages of monetite calcium phosphate (MCP) into desirable 3D matrix cotton using a unique gas foaming technology. These matrix cottons possess biomimetic properties and have oriented porous structures. Using this innovative technique, various shapes of 3D matrix cotton, such as squares, hollow tubes, and other customizable forms, were successfully produced. Importantly, these 3D matrix cottons showed a consistent distribution of monetite particles with total porosity ranging from 90% to 98%. The structure of the 3D matrix cotton, its water/blood absorption capacity, the potential for causing non-hemolysis, and rapid hemostatic properties were thoroughly investigated. Additionally, periodontal cells were cultured on the 3D matrix cotton to assess their viability and morphology, revealing promising results. Furthermore, a coculture study involving NIH-3T3 and MG-63 cells on the 3D matrix cotton showed spheroidal formation within 24 h. Notably, in vitro assessments indicated that the matrix cotton containing 15% monetite (PCL-MMC15%) exhibited superior absorbent capabilities, excellent cell viability, and rapid hemostatic characteristics. Subsequently, the effectiveness of PCL-MMC15% in promoting mandibular bone regeneration was evaluated through an in vivo study on rabbits using a mandibular injury model. The results demonstrated that PCL-MMC15% facilitated the resolution of defects in the mandibular region by initiating new bone formation. Therefore, the presented 3D matrix cotton (PCL-MMC15%) shows significant promise for applications in both mandibular bone regeneration and hemostasis.

Rapid haemostasis to achieve dressing longevity: evaluation trial results using StatSeal catheter exit site protection.

Peripherally inserted central catheters (PICCs) are vital in delivering intravenous therapy. Despite their advantages, PICCs can lead to complications such as catheter exit site bleeding, which can cause patient distress and increase infection risk. This study evaluated the efficacy of StatSeal, a topical haemostatic device, in managing PICC exit site bleeding. StatSeal uses a hydrophilic polymer and potassium ferrate to form a seal, reducing access site bleeding and minimising dressing changes. For this study, Patients were recruited at Frimley Health NHS Foundation Trust; the trial involved 177 patients with StatSeal, and shows that 99% did not require additional dressing changes within the standard 7-day period. The findings demonstrate StatSeal's effectiveness in improving patient outcomes by reducing exit site bleeding and associated complications, enhancing the efficiency of vascular access maintenance and potentially lowering associated healthcare costs. The trial emphasises the importance of innovative solutions such as StatSeal to advance PICC care and improve patient experience.

Amphiphilic Janus cotton gauze with enhanced moisture management and blood coagulation for rapid hemostasis and wound healing

Cotton gauze is commonly used in initial emergency care. However, its high hydrophilicity and limited clotting capacity can lead to the excessive absorption of blood, resulting in unnecessary blood loss. Herein, an amphiphilic Janus cotton gauze with excellent moisture management and enhanced blood coagulation has been developed via in situ generating bioactive glass (BG) onto the cotton gauze (CG), and then attaching cardanol (CA) onto one side of the BG-loaded CG (CG@BG) via click reaction. The Janus gauze (CA-CG@BG) has asymmetric wetting properties with a hydrophilic side (CA-CG@BGHL) and a hydrophobic side (HBCA-CG@BG). When applied to hemostatic, the porous and active BG on CA-CG@BGHL can rapidly initiate coagulation cascade to form a robust thrombus. CA on HBCA-CG@BG can entangled with each other, creating a hydrophobic barrier that prevents blood from flowing out. The hemostatic performance of CA-CG@BG is superior to that of CG in both rats and pigs. Interestingly, CA-CG@BG possesses unidirectional exudate removal. When applied to wound healing, the exudate can penetrate the hydrophobic HBCA-CG@BG to the hydrophilic CA-CG@BGHL, resulting in faster wound healing than CG. CA-CG@BG exhibits excellent cytocompatibility and hemocompatibility. This unique Janus dressing shows promise as a potential material for clinical applications in the future.

Neutrophil extracellular traps-inspired DNA hydrogel for wound hemostatic adjuvant

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.

On-demand engineered double-network gelatin/silicate composited hydrogels with enhanced wet adhesion and stable release of bioactive ion for promoting wound healing

Silicate bioceramics have demonstrated great potential in hydrogel dressings for wound healing due to their special origins of promoting endothelial cell angiogenesis and inhibiting apoptosis of cardiomyocyte. However, there are still some deficiencies, such as insufficient biological activity, instability of silicate ion release, and lower wet adhesion on wounds with tissue exudate, limiting their further clinical applications. Herein, inspired by mussels, a multifunctional double-network hydrogel (FS/PAM-Gel-PDA) wound dressing composited gelatin with silicate ceramic powder with satisfactory wet adhesion, stable release of bioactive ions, hemostasis, and the ability of promoting vascular regeneration was engineered through specifically grafting dopamine to gelatin and introducing ferrous silicate ceramic powder into the hydrogel. The comprehensive experimental results substantiate that the FS/PAM-Gel-PDA has wet-adhesion strength of up to 21.78 kPa, and remains stably adherent to porcine myocardial tissues intuitively after bending, twisting, soaking in water, and stretching. The test results of ion release behavior in vitro show that the oxidation and agglomeration of ferrous silicate ceramic powder can be effectively inhibited by using dopamine to form an antioxidant layer on the surface of ceramic powder, and thus, the stable release of Fe2+ and SiO44− effective ions can be realized. The animal experiment exhibits that FS/PAM-Gel-PDA can achieve rapid hemostasis in the lethal liver defect model. Meanwhile, the FS/PAM-Gel-PDA reveals the remarkable ability to promote wound healing in a full-thickness skin injury model, which can obviously accelerate skin re-epithelialization. To sum up, the FS/PAM-Gel-PDA has excellent wet adhesion and stable release of active ions to accelerate angiogenesis, which shows great potential in promoting wound healing.Graphical

Superporous sponge prepared by secondary network compaction with enhanced permeability and mechanical properties for non-compressible hemostasis in pigs

Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications.

Transformation of Natural Resin Resina Draconis to 3D Functionalized Fibrous Scaffolds for Efficient Chronic Wound Healing.

Chronic wound healing is a major challenge in clinical practice. Secondary dressing damage and antibiotic resistance are the main obstacles for traditional wound dressings. Resina draconis (RD), a natural resin traditionally used in powder form for wound care, is now considered unsuitable due to the lack of gas permeability and moist environment required for wound healing. Here, RD is incorporated in situ by constructing a 3D coiled fibrous scaffold with polycaprolactone/polyethylene oxide. Due to the high porosity of 3D scaffold, the RD-3D dressings have a favorable swelling capacity, providing permeability and moisture for wound repair. Meanwhile, the transformation of RD powder into 3D dressings fully demonstrates capabilities of RD in rapid hemostasis, bactericidal, and inflammation-regulating activities. In vivo evaluations using pressure ulcer and infected wound models confirm the high efficacy of RD-3D dressing in early wound healing, particularly beneficial in the infected wound model compared to recombinant bovine FGF-basic. Further biological analysis shows that resveratrol, loureirin A, and loureirin B, as potentially bioactive components of RD, individually contribute to different aspects of wound healing. Collectively, RD-3D integrated dressings represent a simple, cost-effective, and safe approach to wound healing, providing an alternative therapy for translating medical dressings from bench to bedside.

Tranexamic acid-loaded catechol-modified hyaluronic acid/carboxymethyl chitosan double cross-linked porous gel micropowders for rapid hemostasis and wound healing

Acquiring rapid and effective hemostasis remains a critical clinical challenge. Current researches focus on concentrating blood components to speed up the hemostatic while ignore the effect of anti-fibrinolysis in promoting blood coagulation. Herein, we designed a novel tranexamic acid (TA)-loaded physicochemical double cross-linked multifunctional catechol-modified hyaluronic acid-dopamine/carboxymethyl chitosan porous gel micropowders (TA&Fe3+@HA-DA/CMCS PGMs) for rapid hemostasis and wound healing. TA&Fe3+@HA-DA/CMCS PGMs exhibited high water absorption rate (505.9 ± 62.1 %) and rapid hemostasis (79 ± 4 s) in vivo. Catechol groups, Fe3+ and the protonated amino groups of CMCS induced bacterial death. Moreover, TA&Fe3+@HA-DA/CMCS PGMs displayed sufficient adhesion to a variety of wet rat tissues. TA&Fe3+@HA-DA/CMCS PGMs on various bleeding wounds, including rat liver injury and tail severed models showed excellent hemostasis performance. The TA&Fe3+@HA-DA/CMCS PGMs could promote the healing of full-thickness skin wounds on the backs of rats. The advantages of TA&Fe3+@HA-DA/CMCS PGMs including rapid hemostasis, effective wound healing, good tissue adhesion, antibacterial properties and ease of use make it potentially valuable in clinical application.

Insight into hemostatic performance and mechanism of natural mixed-dimensional Attapulgite clay

Clay minerals have attracted wide attention as biomedical materials due to the unique crystal structure, abundant morphology and good biocompatibility. However, the relevant studies on the abundant natural mixed clay deposits were scarcely reported. Herein, the hemostatic performance of natural mixed-dimensional attapulgite clay (MDAPT) composed of one-dimensional attapulgite and multiple two-dimensional clay were systematically investigated based on the structural evolution using oxalic acid for different time. The results of hemostatic evaluation showed that MDAPT leached by oxalic acid with 1 h presented the shortest clotting time (134 ± 12.17 s), a 15.09 % and 41.74 % reduction of relative hemoglobin absorbance at 180 s and 120 s when compared with the control group, respectively, and an increase of 19.45 % of the blood clotting index in vitro, as well as MDAPT obtained the shortest bleeding time (158.5 ± 6.9 s), nearly 66 % and 31 % reduction blood loss as compared to the blank group and the YNBY group in vivo. This improvement was primarily ascribed to the synergistic effect of lamellar non-expandable illite, and nano rod-like attapulgite. Furthermore, the rapid hemostasis of MDAPT was also due to the joint effect of superhydrophobic property toward blood, minimizing blood loss, surface negative charge, metal ions from MDAPT structural skeleton, promoting an average increase of 21 % for platelet activation. The results suggested that MDAPT could be served as a promising efficient inorganic hemostatic materials, which provided a feasible strategy to realize the high-valued utilization of natural mixed clay resources.

Platelet-Rich Plasma-Embedded Porous Polycaprolactone Film with a Large Surface Area for Effective Hemostasis.

Uncontrollable and widespread bleeding caused by surgery or sudden accidents can lead to death if not treated with appropriate hemostasis. To prevent excessive life-threatening bleeding, various hemostatic agents based on polymeric biomaterials with various additives for accelerated blood coagulation have been adopted in clinical fields. In particular, platelet-rich plasma (PRP), which contains many blood coagulation factors that can accelerate blood clot formation, is considered as one of the most effective hemostatic additives. We investigated a PRP-embedded porous film using discarded (expired) PRP and a film with a leaf-stacked structure (FLSS), as a hemostatic agent to induce rapid hemostasis. The film, which contained an LSS on one side (PCL-FLSS), was fabricated by a simple heating-cooling technique using tetraglycol and polycaprolactone (PCL) film. Activated PRP was obtained by the thawing of frozen PRP at the end of its expiration date (the platelet cell membrane is disrupted during the freezing and thawing of PRP, thus releasing various coagulation factors) and embedded in the PCL-FLSS (PRP-FLSS). From in vitro and in vivo experiments using a rat hepatic bleeding model, it was recognized that PRP-FLSS is not only biocompatible but also significantly accelerates blood clotting and thus prevents rapid bleeding, probably due to a synergistic effect of the sufficient supply of various blood coagulants from activated PRP embedded in the LSS layer and the large surface area of the LSS itself. The study suggests that PRP-FLSS, a combination of a porous polymer matrix with a unique morphology and discarded biofunctional resources, can be an advanced hemostatic agent as well as an upcycling platform to avoid the waste of biofunctional resources.

A bioactive composite sponge based on biomimetic collagen fibril and oxidized alginate for noncompressible hemorrhage and wound healing

The study focuses on developing a bioactive shape memory sponge to address the urgent demand for short-term rapid hemostasis and long-term wound healing in noncompressible hemorrhage cases. A composite sponge was created by spontaneously generating pores and double cross-linking under mild conditions using biomimetic collagen fibril (BCF) and oxidized alginate (OA) as natural backbone, combined with an inert calcium source (Ca) from CaCO3-GDL slow gelation mechanism. The optimized BCF/OACa (5/5) sponge efficiently absorbed blood after compression and recovered to its original state within 11.2 ± 1.3 s, achieving physical hemostatic mechanism. The composite sponge accelerated physiological coagulation by promoting platelet adhesion and activation through BCF, as well as enhancing endogenous and exogenous hemostatic pathways by Ca2+. Compared to commercial PVA expanding hemostatic sponge, the composite sponge reduced bleeding volume and shortened hemostasis time in rat liver injury pick and perforation wound models. Additionally, it stimulated fibroblast migration and differentiation, thus promoting wound healing. It is biodegradable with low inflammatory response and promotes granulation tissue regeneration. In conclusion, this biocomposite sponge provides multiple hemostatic pathways and biochemical support for wound healing, is biologically safe and easy to fabricate, process and use, with significant potential for clinical translation and application.

PALC-02. PALLIATIVE RADIOTHERAPY FOR HAEMOSTASIS IN CHILDREN WITH CEREBRAL METASTATIC HAEMORRHAGE

Abstract BACKGROUND Among children, bleeding from brain metastases is rare. Bleeding could be caused by: cancer, treatments and chemotherapy/other drugs such as Bevacizumab, NSAIDs and anticoagulants. We report a case of brain RT after metastases bleeding. METHODS A 14-years-old boy with a negative previous medical history presented to the Emergency Department with seizures and loss of consciousness. Full-body CT scan revealed brain and renal haemorrhages and a right testicular lesion. Serum βhCG was 223,773 mIU/mL. Neurosurgical bleeding control and right orchiectomy were performed: the histopathology revealed a metastatic mixed non-seminomatous germ cell neoplasia of the testis. First-line chemotherapy (4 cycles of Cisplatin/Etoposide/Ifosfamide) and second-line treatments (Paclitaxel/Ifosfamide/Cisplatin and Gemcitabine/Paclitaxel/Oxaliplatin) were performed. Suddenly, he presented with left-sided hyposthenia and partial left hemibody seizure. CT scan revealed 2 haemorrhagic brain lesions, one in each hemisphere. Surgery was not feasible. We started anti-oedema and anti-epileptic therapy, and whole brain RT (WBRT, 36 Gy/12 fx, BEDα/β= 10 Gy= 46.8 Gy). After 5 days from the start, RT had a 7-day stop because of acute oedema and clinical deterioration. Fourth-line chemotherapy was administered with CarboPEB (1st of further 4 cycles), and then WBRT was restarted. At the end of WBRT a stereotactic RT boost to both the haemorrhagic lesions was delivered (20 Gy/10 fx, BEDα/β= 10 Gy= 24.0 Gy). As of today, eight months after the end of therapy, the patient is free from disease and βhCG is negative. CONCLUSION Palliative RT in children is a non-conventional indication, but potentially effective at providing rapid haemostasis, especially in selected cases (surgery not feasible/contraindicated, adult-type histologies, …) and it is ensuring a good tumor control and low-grade acute toxicities. Hypofractionation is suggested to balance patient comfort and treatment effectiveness, especially when life expectancy is short. The optimal RT schedule, dose and fractionations need to be further investigated.

Marine‐Derived Nanozyme‐Crosslinked Self‐Adaptive Hydrogels for Programmed Regulating the Regeneration Process

AbstractSelf‐adaptive hydrogels that can specifically respond to pathological cues and match the highly ordered tissue regeneration process are significantly on‐demand for effective wound management. Herein, multifunctional marine‐derived gold clusterzyme (AuNCs)‐based self‐adaptive hydrogels with microenvironment triggered release behavior are elaborately fabricated for on‐demand antioxidant, anti‐inflammatory and immunoregulation. The marine mussel‐derived catechol ligands (L‐3,4‐dihydroxyphenylalanine) endow AuNCs with enhanced superoxide dismutase‐mimic activity due to their high affinity to superoxide anion free radical (O2−•) and unique electron transfer mechanism, leading to 100% inhibition of O2−•. Upon uniformly crosslinking with phenylboronic acid‐modified marine‐derived sodium alginate (PBA‐Sa), the obtained AuNCs@PBA‐Sa hydrogels exhibit outstanding self‐healing property, tunable degradation and good removability. Meanwhile, AuNCs can greatly enhance the mechanical property and confer the hydrogel with favorable tissue adhesion for rapid hemostasis. Furthermore, injectable AuNCs@PBA‐Sa hydrogels can not only adapt their shape to the irregular wound, but also smartly adapt their microstructure to the physiological microenvironment of diabetic wound, leading to the responsive release of AuNCs upon the break of boronate ester bonds. The released gold clusterzymes can actively induce the generation of M2‐macrophage, demonstrating an outstanding anti‐inflammatory and pro‐regeneration effect. Therefore, the present multifunctional clusterzyme‐based self‐adaptive hydrogels hold great potential for remolding the dynamic tissue regeneration microenvironment and smart wound management.