Uncontrollable non-compressible hemorrhage and traumatic infection have been major causes of mortality and disability in both civilian and military populations.A dressing designed for point-of-care control of noncompr...Uncontrollable non-compressible hemorrhage and traumatic infection have been major causes of mortality and disability in both civilian and military populations.A dressing designed for point-of-care control of noncompressible hemorrhage and prevention of traumatic infections represents an urgent medical need.Here,a novel self-gelling sponge OHN@ε-pL is developed,integrating N-succinimidyl ester oxidized hyaluronic acid(OHN)andε-poly-L-lysine(ε-pL).Upon application to the wound site,the sponge can rapidly absorb interfacial fluids and undergo a phase transition from sponge to gel.The transformed gel facilitates robust tissue adhesion and achieves synergistic hemostasis by enriching coagulation factors within the sponge phase and providing a barrier effect in the gel phase.The in vitro and in vivo studies revealed that the optimized OHN@ε-pL_(3) sponge possesses self-gelling capability,tissue adhesion,enhanced coagulation ability,and exhibits excellent biocompatibility and antibacterial efficacy.In hemostasis,OHN@ε-pL_(3) sponges exhibited reduced blood loss and decreased hemostatic time compared to commercial hemostatic agents,as demonstrated in rat liver,femoral vein,and tail truncation bleeding models.Furthermore,the OHN@ε-pL_(3) sponge exhibited superior performance in accelerating wound closure and healing of S.aureus-infected wounds.Collectively,OHN@ε-pL sponges represent a promising candidate for medical dressings,specifically for managing uncontrollable noncompressible hemorrhage and traumatic infections.展开更多
Traditional hemostatic materials are difficult to meet the needs of non-compressible bleeding and for coagulopathic patients.In addition,open wounds are susceptible to infection,and then develop into chronic wounds.Ho...Traditional hemostatic materials are difficult to meet the needs of non-compressible bleeding and for coagulopathic patients.In addition,open wounds are susceptible to infection,and then develop into chronic wounds.However,the development of integrated dressings that do not depend on coagulation pathway and improve the microenvironment of chronic wounds remains a challenge.Inspired by the porous structure and composition of the natural extracellular matrix,adipic dihydrazide modified gelatin(GA),dodecylamine-grafted hyaluronic acid(HD),and MnO_(2) nanozyme(manganese dioxide)@DFO(deferoxamine)@PDA(polydopamine)(MDP)nanoparticles were combined to prepare GA/HD/MDP cryogels through amidation reaction and hydrogen bonding.These cryogels exhibited good fatigue resistance,photothermal antibacterial(about 98%killing ratios of both Escherichia coli and methicillin-resistant Staphylococcus aureus(MRSA)after 3 min near-infrared irradiation),reactive oxygen species scavenging,oxygen release,and angiogenesis properties.Furthermore,in the liver defect model of rats with coagulopathy,the cryogel displayed less bleeding and shorter hemostasis time than commercial gelatin sponge.In MRSA-infected diabetic wounds,the cryogel could decrease wound inflammation and oxidative stress,alleviate the hypoxic environment,promote collagen deposition,and induce vascular regeneration,showing a better repair effect compared with the Tegaderm^(TM)film.These results indicated that GA/HD/MDP cryogels have great potential in non-compressible hemorrhage for coagulopathic patients and in healing infected wounds for diabetic patients.展开更多
Background: In combat operations, patients with traumatic injuries require expeditious evacuation to improve survival. Studies have shown that long transport times are associated with increased morbidity and mortality...Background: In combat operations, patients with traumatic injuries require expeditious evacuation to improve survival. Studies have shown that long transport times are associated with increased morbidity and mortality. Limited data exist on the influence of transport time on patient outcomes with specific injury types. The objective of this study was to determine the impact of the duration of time from the initial request for medical evacuation to arrival at a medical treatment facility on morbidity and mortality in casualties with traumatic extremity amputation and noncompressible torso injury(NCTI).Methods: We completed a retrospective review of MEDEVAC patient care records for United States military personnel who sustained traumatic amputations and NCTI during Operation Enduring Freedom between January 2011 and March 2014. We grouped patients as traumatic amputation and NCTI(AMP+NCTI), traumatic amputation only(AMP),and neither AMP nor NCTI(Non-AMP/NCTI). Analysis was performed using chi-squared tests, Fisher's exact tests,Cochran-Armitage Trend tests, Shapiro-Wilks tests, Wilcoxon and Kruskal-Wallis techniques and Cox proportional hazards regression modeling.Results: We reviewed 1267 records, of which 669 had an injury severity score(ISS) of 10 or greater and were included in the analysis. In the study population, 15.5% sustained only amputation injuries(n=104, AMP only), 10.8% sustained amputation and NCTI(n=72, AMP+NCTI), and 73.7% did not sustain either an amputation or an NCTI(n=493,Non-AMP/NCTI). AMP+NCTI had the highest mortality(16.7%) with transport time greater than 60 min. While the AMP+NCTI group had decreasing survival with longer transport times, AMP and Non-AMP/NCTI did not exhibit the same trend.Conclusions: A decreased transport time from the point of injury to a medical treatment facility was associated with decreased mortality in patients who suffered a combination of amputation injury and NCTI. No significant association between transport time and outcomes was found in patients who did not sustain NCTI. Priority for rapid evacuation of combat casualties should be given to those with NCTI.展开更多
BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBO...BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBOA)can alleviate ischemic burden;however,its security and eff ectiveness prior to operative hemorrhage control remains unknown.Hence,we aimed to estimate the effi cacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun.METHODS:Twenty Landrace pigs were randomized into control(no aortic occlusion)(n=5),intervention with complete REBOA(cREBOA)(n=5),continuous pREBOA(C-pREBOA)(n=5),and sequential pREBOA(S-pREBOA)(n=5)groups.In the cREBOA and C-pREBOA groups,the balloon was inflated for 60 min.The hemodynamic and laboratory values were compared at various observation time points.Tissue samples immediately after animal euthanasia from the myocardium,liver,kidneys,and duodenum were collected for histological assessment using hematoxylin and eosin staining.RESULTS:Compared with the control group,the survival rate of the REBOA groups was prominently improved(all P<0.05).The total volume of blood loss was markedly lower in the cREBOA group(493.14±127.31 mL)compared with other groups(P<0.01).The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups(P<0.05).At 120 min,the S-pREBOA group showed higher alanine aminotransferase(P<0.05)but lower blood urea nitrogen compared with the cREBOA group(P<0.05).CONCLUSION:In this trauma model with liver injury,a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure,despite persistent hemorrhage.Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures,and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.展开更多
Non-compressible hemorrhage poses a severe threat to life globally,yet achieving effective hemostasis and facilitating tissue repair remain a significant challenge and desired requirement.Herein,the all-in-one extra-c...Non-compressible hemorrhage poses a severe threat to life globally,yet achieving effective hemostasis and facilitating tissue repair remain a significant challenge and desired requirement.Herein,the all-in-one extra-cellular matrix(ECM)-based powder,composed of modified small intestinal submucosa(SIS)and sodium algi-nate,was ingeniously designed to realize one-stop management for non-compressible hemorrhage.Specifically,upon contact bleeding site,the powder’s extreme liquid absorption allows for the rapid removal of interfacial blood.Simultaneously,based on the instant self-assembly strategy of covalent/non-covalent interaction,the powder can transform to wet bio-adhesive hydrogel within 5 s,effectively sealing the wound.Using the inherent bioactivities,the ECM-based powder exhibits satisfactory biocompatibility,enhanced cell recruitment,angio-genesis and endothelial cell functions.Ulteriorly,excellent hemostasis performance have verified in rabbit liver non-compressible hemorrhage and heart/artery massive hemorrhage models,significantly reducing the blood loss.More importantly,after hemostasis,the impaired liver demonstrates functional restoration that the more vessels and bile ducts formation,facilitated by the biodegradation of ECM-derived powders in vivo and the multi-biological cues response.Collectively,leveraging the merits of powder and hydrogel,this novel powder fulfills the all-in-one need for both non-compressible hemorrhage control and subsequent tissue repair,signifying it a valuable material in first aid.展开更多
基金supported by the China Postdoctoral Science Foundation(Grant No.2023M740626)National Natural Science Foundation of China(Grant No.82102324)Natural Science Foundation of Chongqing(Grant No.CSTB2022BSXM-JCX0028).
文摘Uncontrollable non-compressible hemorrhage and traumatic infection have been major causes of mortality and disability in both civilian and military populations.A dressing designed for point-of-care control of noncompressible hemorrhage and prevention of traumatic infections represents an urgent medical need.Here,a novel self-gelling sponge OHN@ε-pL is developed,integrating N-succinimidyl ester oxidized hyaluronic acid(OHN)andε-poly-L-lysine(ε-pL).Upon application to the wound site,the sponge can rapidly absorb interfacial fluids and undergo a phase transition from sponge to gel.The transformed gel facilitates robust tissue adhesion and achieves synergistic hemostasis by enriching coagulation factors within the sponge phase and providing a barrier effect in the gel phase.The in vitro and in vivo studies revealed that the optimized OHN@ε-pL_(3) sponge possesses self-gelling capability,tissue adhesion,enhanced coagulation ability,and exhibits excellent biocompatibility and antibacterial efficacy.In hemostasis,OHN@ε-pL_(3) sponges exhibited reduced blood loss and decreased hemostatic time compared to commercial hemostatic agents,as demonstrated in rat liver,femoral vein,and tail truncation bleeding models.Furthermore,the OHN@ε-pL_(3) sponge exhibited superior performance in accelerating wound closure and healing of S.aureus-infected wounds.Collectively,OHN@ε-pL sponges represent a promising candidate for medical dressings,specifically for managing uncontrollable noncompressible hemorrhage and traumatic infections.
基金jointly supported by the National Natural Science Foundation of China(No.52273149,82171143)Fundamental Research Funds for the Central Universities and the World-Class Universities(Disciplines)Characteristic Development Guidance Funds for the Central Universities.
文摘Traditional hemostatic materials are difficult to meet the needs of non-compressible bleeding and for coagulopathic patients.In addition,open wounds are susceptible to infection,and then develop into chronic wounds.However,the development of integrated dressings that do not depend on coagulation pathway and improve the microenvironment of chronic wounds remains a challenge.Inspired by the porous structure and composition of the natural extracellular matrix,adipic dihydrazide modified gelatin(GA),dodecylamine-grafted hyaluronic acid(HD),and MnO_(2) nanozyme(manganese dioxide)@DFO(deferoxamine)@PDA(polydopamine)(MDP)nanoparticles were combined to prepare GA/HD/MDP cryogels through amidation reaction and hydrogen bonding.These cryogels exhibited good fatigue resistance,photothermal antibacterial(about 98%killing ratios of both Escherichia coli and methicillin-resistant Staphylococcus aureus(MRSA)after 3 min near-infrared irradiation),reactive oxygen species scavenging,oxygen release,and angiogenesis properties.Furthermore,in the liver defect model of rats with coagulopathy,the cryogel displayed less bleeding and shorter hemostasis time than commercial gelatin sponge.In MRSA-infected diabetic wounds,the cryogel could decrease wound inflammation and oxidative stress,alleviate the hypoxic environment,promote collagen deposition,and induce vascular regeneration,showing a better repair effect compared with the Tegaderm^(TM)film.These results indicated that GA/HD/MDP cryogels have great potential in non-compressible hemorrhage for coagulopathic patients and in healing infected wounds for diabetic patients.
基金Department of Defense Joint Program Committee(JPC-6)
文摘Background: In combat operations, patients with traumatic injuries require expeditious evacuation to improve survival. Studies have shown that long transport times are associated with increased morbidity and mortality. Limited data exist on the influence of transport time on patient outcomes with specific injury types. The objective of this study was to determine the impact of the duration of time from the initial request for medical evacuation to arrival at a medical treatment facility on morbidity and mortality in casualties with traumatic extremity amputation and noncompressible torso injury(NCTI).Methods: We completed a retrospective review of MEDEVAC patient care records for United States military personnel who sustained traumatic amputations and NCTI during Operation Enduring Freedom between January 2011 and March 2014. We grouped patients as traumatic amputation and NCTI(AMP+NCTI), traumatic amputation only(AMP),and neither AMP nor NCTI(Non-AMP/NCTI). Analysis was performed using chi-squared tests, Fisher's exact tests,Cochran-Armitage Trend tests, Shapiro-Wilks tests, Wilcoxon and Kruskal-Wallis techniques and Cox proportional hazards regression modeling.Results: We reviewed 1267 records, of which 669 had an injury severity score(ISS) of 10 or greater and were included in the analysis. In the study population, 15.5% sustained only amputation injuries(n=104, AMP only), 10.8% sustained amputation and NCTI(n=72, AMP+NCTI), and 73.7% did not sustain either an amputation or an NCTI(n=493,Non-AMP/NCTI). AMP+NCTI had the highest mortality(16.7%) with transport time greater than 60 min. While the AMP+NCTI group had decreasing survival with longer transport times, AMP and Non-AMP/NCTI did not exhibit the same trend.Conclusions: A decreased transport time from the point of injury to a medical treatment facility was associated with decreased mortality in patients who suffered a combination of amputation injury and NCTI. No significant association between transport time and outcomes was found in patients who did not sustain NCTI. Priority for rapid evacuation of combat casualties should be given to those with NCTI.
基金supported by military logistics scientific research project(AHJ16J004)。
文摘BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBOA)can alleviate ischemic burden;however,its security and eff ectiveness prior to operative hemorrhage control remains unknown.Hence,we aimed to estimate the effi cacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun.METHODS:Twenty Landrace pigs were randomized into control(no aortic occlusion)(n=5),intervention with complete REBOA(cREBOA)(n=5),continuous pREBOA(C-pREBOA)(n=5),and sequential pREBOA(S-pREBOA)(n=5)groups.In the cREBOA and C-pREBOA groups,the balloon was inflated for 60 min.The hemodynamic and laboratory values were compared at various observation time points.Tissue samples immediately after animal euthanasia from the myocardium,liver,kidneys,and duodenum were collected for histological assessment using hematoxylin and eosin staining.RESULTS:Compared with the control group,the survival rate of the REBOA groups was prominently improved(all P<0.05).The total volume of blood loss was markedly lower in the cREBOA group(493.14±127.31 mL)compared with other groups(P<0.01).The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups(P<0.05).At 120 min,the S-pREBOA group showed higher alanine aminotransferase(P<0.05)but lower blood urea nitrogen compared with the cREBOA group(P<0.05).CONCLUSION:In this trauma model with liver injury,a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure,despite persistent hemorrhage.Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures,and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.
基金Sichuan Science and Tech-nology Program(2024NSFSC0002,MZGC20240011)the National Natural Science Foundation of China(324B2047)+3 种基金“1.3.5”Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD23037)the Frontiers Medical Center,Tianfu Jincheng Lab-oratory Foundation(TFJC2023010002)Dai-Bing Luo(Analytical&Testing Center,Sichuan University)Mao-Jia Chen and Jie-Hao Chen(Animal Laboratory Center,West China Hospital,Sichuan University)for the support in mechanical testing and animal experiment,respectively.
文摘Non-compressible hemorrhage poses a severe threat to life globally,yet achieving effective hemostasis and facilitating tissue repair remain a significant challenge and desired requirement.Herein,the all-in-one extra-cellular matrix(ECM)-based powder,composed of modified small intestinal submucosa(SIS)and sodium algi-nate,was ingeniously designed to realize one-stop management for non-compressible hemorrhage.Specifically,upon contact bleeding site,the powder’s extreme liquid absorption allows for the rapid removal of interfacial blood.Simultaneously,based on the instant self-assembly strategy of covalent/non-covalent interaction,the powder can transform to wet bio-adhesive hydrogel within 5 s,effectively sealing the wound.Using the inherent bioactivities,the ECM-based powder exhibits satisfactory biocompatibility,enhanced cell recruitment,angio-genesis and endothelial cell functions.Ulteriorly,excellent hemostasis performance have verified in rabbit liver non-compressible hemorrhage and heart/artery massive hemorrhage models,significantly reducing the blood loss.More importantly,after hemostasis,the impaired liver demonstrates functional restoration that the more vessels and bile ducts formation,facilitated by the biodegradation of ECM-derived powders in vivo and the multi-biological cues response.Collectively,leveraging the merits of powder and hydrogel,this novel powder fulfills the all-in-one need for both non-compressible hemorrhage control and subsequent tissue repair,signifying it a valuable material in first aid.
