Traumatic brain injury (TBI) represents a major global health challenge due to its complex pathophysiology and long-term neurological sequelae.Current treatments are insufficient to promote neural repair and functiona...Traumatic brain injury (TBI) represents a major global health challenge due to its complex pathophysiology and long-term neurological sequelae.Current treatments are insufficient to promote neural repair and functional recovery,highlighting the urgent need for innovative strategies.Biomaterial-based approaches have emerged as transformative solutions,offering new possibilities for TBI treatment and cranial repair.This review explores the role of extracellular matrix (ECM) simulation in TBI repair,emphasizing ECM-inspired biomaterials that replicate natural microenvironments to support cell adhesion,migration,and differentiation.Advanced biomaterials regulate cell behavior through biophysical and biochemicalcues,enhancing neural regeneration.Strategies for activating key signaling pathways,such as PI3K/Akt and Nrf2/HO-1,are discussed,showing how biomaterials promote neuroprotection,reduce inflammation,and support tissue repair.The review also highlights the potential of 3D printing technology to design personalized scaffolds to address TBI repair's structural and functional complexities.Finally,neural interfaces are presented as cutting-edge bioelectronic systems that integrate with neural tissues,reducing mechanical mismatch and promoting functional recovery.These interfaces provide a platform for precise neural stimulation and real-time monitoring.By integrating ECM simulation,advanced biomaterials,3D printing,and neural interfaces,this review provides a comprehensive framework for addressing the challenges of TBI repair.These innovations hold promise for developing personalized,next-generation therapies to improve patient outcomes and advance regenerative medicine.Future researchshould focus on developing dynamic,intelligent biomaterials,advancing 3D printing for precise tissue reconstruction,and integrating biomaterials with gene and drug therapies to create personalized,multi-faceted treatment approaches for traumatic brain injury repair.展开更多
Arterial thrombosis is in part contributed by excessive platelet aggregation,which can lead to blood clotting and subsequent heart attack and stroke.Platelets are sensitive to the haemodynamic environment.Rapid haemod...Arterial thrombosis is in part contributed by excessive platelet aggregation,which can lead to blood clotting and subsequent heart attack and stroke.Platelets are sensitive to the haemodynamic environment.Rapid haemodynamcis and disturbed blood flow,which occur in vessels with growing thrombi and atherosclerotic plaques or is caused by medical device implantation and intervention,promotes platelet aggregation and thrombus formation.In such situations,conventional antiplatelet drugs often have suboptimal efficacy and a serious side effect of excessive bleeding.Investigating the mechanisms of platelet biomechanical activation provides insights distinct from the classic views of agonist-stimulated platelet thrombus formation.In this work,we review the recent discoveries underlying haemodynamic force-reinforced platelet binding and mechanosensing primarily mediated by three platelet receptors:glycoprotein Ib(GPIb),glycoprotein IIb/IIIa(GPIIb/IIIa)and glycoprotein VI(GPVI),and their implications for development of antithrombotic‘mechano-medicine’.展开更多
Cerebral venous sinus thrombosis(CVST)is a type of stroke associated with COVID-19 vaccine-induced immune thrombotic thrombocytopenia.The precise etiology of CVST often remains elusive due to the highly heterogeneous ...Cerebral venous sinus thrombosis(CVST)is a type of stroke associated with COVID-19 vaccine-induced immune thrombotic thrombocytopenia.The precise etiology of CVST often remains elusive due to the highly heterogeneous nature of its governing mechanisms,specifically,Virchow’s triad that involves altered blood flow,endothelial dysfunction,and hypercoagulability,which varies substantially amongst individuals.Existing diagnostic and monitoring approaches lack the capability to reflect the combination of these patient-specific thrombotic determinants.In response to this challenge,we introduce a Vein-Chip platform that recapitulates the CVST vascular anatomy from magnetic resonance venography and the associated hemodynamic flow profile using the“Chinese Movable Type-like”soft stereolithography technique.The resultant full-lumen personalized Vein-Chips,functionalized with endothelial cells,enable in-vitro thrombosis assays that can elucidate distinct thrombogenic scenarios between normal vascular conditions and those of endothelial dysfunction.The former displayed minimal platelet aggregation and negligible fibrin deposition,while the latter presented significant fibrin extrusion from platelet aggregations.The low-cost movable typing technique further enhances the potential for commercialization and broader utilization of personalized Vein-Chips in surgical labs and at-home monitoring.Future research and development in this direction will pave the way for improved management and prevention of CVST,ultimately benefiting both patients and healthcare systems.展开更多
Thrombosis,a leading cause of cardiovascular morbidity and mortality,involves the formation of blood clots within blood vessels.Current animal models and in vitro systems have limitations in recapitulating the complex...Thrombosis,a leading cause of cardiovascular morbidity and mortality,involves the formation of blood clots within blood vessels.Current animal models and in vitro systems have limitations in recapitulating the complex human vasculature and hemodynamic conditions,limiting the research in understanding the mechanisms of thrombosis.Bioprinting has emerged as a promising approach to construct biomimetic vascular models that closely mimic the structural and mechanical properties of native blood vessels.This review discusses the key considerations for designing bioprinted vascular conduits for thrombosis studies,including the incorporation of key structural,biochemical and mechanical features,the selection of appropriate biomaterials and cell sources,and the challenges and future directions in the field.The advancements in bioprinting techniques,such as multimaterial bioprinting and microfluidic integration,have enabled the development of physiologically relevant models of thrombosis.The future of bioprinted models of thrombosis lies in the integration of patient-specific data,real-time monitoring technologies,and advanced microfluidic platforms,paving the way for personalized medicine and targeted interventions.As the field of bioprinting continues to evolve,these advanced vascular models are expected to play an increasingly important role in unraveling the complexities of thrombosis and improving patient outcomes.The continued advancements in bioprinting technologies and the collaboration between researchers from various disciplines hold great promise for revolutionizing the field of thrombosis research.展开更多
Addressing the pressing demand for rapid and inexpensive coagulation testing in cardiovascular care,this study introduces a novel application of repurposed COVID-19 rapid antigen tests(RATs)as paper-based lateral flow...Addressing the pressing demand for rapid and inexpensive coagulation testing in cardiovascular care,this study introduces a novel application of repurposed COVID-19 rapid antigen tests(RATs)as paper-based lateral flow assays(LFAs)combined with machine learning for coagulation status evaluation.By further developing a mobile app prototype,we present a platform that enables clinicians to perform immediate and accurate anticoagulant dosing adjustments using existing post-pandemic resources.Our proof-of-concept employs a random forest machine learning classifier to interpret image feature variations on RAT NC membrane,correlating red blood cell(RBC)wicked diffusion distance in recalcified citrated whole blood with changes in coagulative viscosity,easily interpreted.Enhanced by confocal imaging studies of paper microfluidics,our approach provides insights into the mechanisms dissecting coagulation components,achieving high classification precision,recall,and F1-scores.The inverse relationship between RBC wicked diffusion distance and enoxaparin concentration paves the way for machine learning to inform real-time dose prescription adjustments,aligning with individual patient profiles to optimize therapeutic outcomes.This study not only demonstrates the potential of leveraging surplus RATs for coagulation management but also exemplifies a cost-effective,rapid,and smart strategy to enhance clinical decision-making in the post-pandemic era.展开更多
基金financially supported by the Natural Science Foundation of Sichuan(No.2022NSFSC1474)Sichuan Administration of Traditional Chinese Medicine Research Special Foundation(No.2024zd034)
文摘Traumatic brain injury (TBI) represents a major global health challenge due to its complex pathophysiology and long-term neurological sequelae.Current treatments are insufficient to promote neural repair and functional recovery,highlighting the urgent need for innovative strategies.Biomaterial-based approaches have emerged as transformative solutions,offering new possibilities for TBI treatment and cranial repair.This review explores the role of extracellular matrix (ECM) simulation in TBI repair,emphasizing ECM-inspired biomaterials that replicate natural microenvironments to support cell adhesion,migration,and differentiation.Advanced biomaterials regulate cell behavior through biophysical and biochemicalcues,enhancing neural regeneration.Strategies for activating key signaling pathways,such as PI3K/Akt and Nrf2/HO-1,are discussed,showing how biomaterials promote neuroprotection,reduce inflammation,and support tissue repair.The review also highlights the potential of 3D printing technology to design personalized scaffolds to address TBI repair's structural and functional complexities.Finally,neural interfaces are presented as cutting-edge bioelectronic systems that integrate with neural tissues,reducing mechanical mismatch and promoting functional recovery.These interfaces provide a platform for precise neural stimulation and real-time monitoring.By integrating ECM simulation,advanced biomaterials,3D printing,and neural interfaces,this review provides a comprehensive framework for addressing the challenges of TBI repair.These innovations hold promise for developing personalized,next-generation therapies to improve patient outcomes and advance regenerative medicine.Future researchshould focus on developing dynamic,intelligent biomaterials,advancing 3D printing for precise tissue reconstruction,and integrating biomaterials with gene and drug therapies to create personalized,multi-faceted treatment approaches for traumatic brain injury repair.
基金supported by grants from Sydney Research Accelerator(SOAR)prize(L.A.J.)The Royal College of Pathologists of Australasia Kanematsu research award(L.A.J.)+2 种基金the Cardiac Society of Australia and New Zealand BAYER Young Investigator Research Grant(L.A.J.)We thank Zaverio Ruggeri,Yilong Wang,Liping Liu,Jing-fei Dong and Yi Qian for helpful discussion.Y.C.is a MERU(Medolago-Ruggeri)Foundation post-doctoral awardee.L.A.J.is an Australian Research Council DECRA fellow(DE190100609)a National Heart Foundation Future Leader fellow(102532).
文摘Arterial thrombosis is in part contributed by excessive platelet aggregation,which can lead to blood clotting and subsequent heart attack and stroke.Platelets are sensitive to the haemodynamic environment.Rapid haemodynamcis and disturbed blood flow,which occur in vessels with growing thrombi and atherosclerotic plaques or is caused by medical device implantation and intervention,promotes platelet aggregation and thrombus formation.In such situations,conventional antiplatelet drugs often have suboptimal efficacy and a serious side effect of excessive bleeding.Investigating the mechanisms of platelet biomechanical activation provides insights distinct from the classic views of agonist-stimulated platelet thrombus formation.In this work,we review the recent discoveries underlying haemodynamic force-reinforced platelet binding and mechanosensing primarily mediated by three platelet receptors:glycoprotein Ib(GPIb),glycoprotein IIb/IIIa(GPIIb/IIIa)and glycoprotein VI(GPVI),and their implications for development of antithrombotic‘mechano-medicine’.
基金National Health and Medical Research Council(NHMRC)of Australia,Grant/Award Numbers:APP2003904,GNT2022247NSW Cardiovascular Capacity Building Program,Grant/Award Number:Early-Mid Career Researcher Grant+7 种基金MRFF Cardiovascular Health Mission Grants,Grant/Award Numbers:APP2016165,APP2023977Ramaciotti Foundations,Grant/Award Number:2020HIG76National Heart Foundation,Grant/Award Numbers:106979,106879Office of Global and Research Engagement,Grant/Award Number:International Sustainable Development Goal ProgramSydney Nano Research Schemes,Grant/Award Number:Grand ChallengeNational Heart Foundation Future Leader Fellow Level 2,Grant/Award Number:105863Snow Medical Research Foundation Fellow,Grant/Award Number:2022SF176New South Wales Government。
文摘Cerebral venous sinus thrombosis(CVST)is a type of stroke associated with COVID-19 vaccine-induced immune thrombotic thrombocytopenia.The precise etiology of CVST often remains elusive due to the highly heterogeneous nature of its governing mechanisms,specifically,Virchow’s triad that involves altered blood flow,endothelial dysfunction,and hypercoagulability,which varies substantially amongst individuals.Existing diagnostic and monitoring approaches lack the capability to reflect the combination of these patient-specific thrombotic determinants.In response to this challenge,we introduce a Vein-Chip platform that recapitulates the CVST vascular anatomy from magnetic resonance venography and the associated hemodynamic flow profile using the“Chinese Movable Type-like”soft stereolithography technique.The resultant full-lumen personalized Vein-Chips,functionalized with endothelial cells,enable in-vitro thrombosis assays that can elucidate distinct thrombogenic scenarios between normal vascular conditions and those of endothelial dysfunction.The former displayed minimal platelet aggregation and negligible fibrin deposition,while the latter presented significant fibrin extrusion from platelet aggregations.The low-cost movable typing technique further enhances the potential for commercialization and broader utilization of personalized Vein-Chips in surgical labs and at-home monitoring.Future research and development in this direction will pave the way for improved management and prevention of CVST,ultimately benefiting both patients and healthcare systems.
基金supported by the National Health and Medical Research Council(NHMRC)of Australia(APP2003904-L.A.J.)NSW Cardiovascular Capacity Building Program(Early-Mid Career Researcher Grant-L.A.J.,H22/98586-K.L.)+7 种基金MRFF Cardiovascular Health Mission Grants(MRF2016165-L.A.J.,MRF2023977-L.A.J.)MRFF Early to Mid-Career Researchers Grant(MRF2028865-L.A.J.)NSW Government Boosting Business Innovation Program(BBIP)International Stream(L.A.J.)National Heart Foundation Vanguard Grant(106979-L.A.J.)Office of Global and Research Engagement(International Sustainable Development Goal Program-L.A.J.)a Snow Medical Research Foundation Fellow(2022SF176)a National Heart Foundation Future Leader Fellow Level 2(105863)an Australian Research Council Future Fellow(FT230100249).
文摘Thrombosis,a leading cause of cardiovascular morbidity and mortality,involves the formation of blood clots within blood vessels.Current animal models and in vitro systems have limitations in recapitulating the complex human vasculature and hemodynamic conditions,limiting the research in understanding the mechanisms of thrombosis.Bioprinting has emerged as a promising approach to construct biomimetic vascular models that closely mimic the structural and mechanical properties of native blood vessels.This review discusses the key considerations for designing bioprinted vascular conduits for thrombosis studies,including the incorporation of key structural,biochemical and mechanical features,the selection of appropriate biomaterials and cell sources,and the challenges and future directions in the field.The advancements in bioprinting techniques,such as multimaterial bioprinting and microfluidic integration,have enabled the development of physiologically relevant models of thrombosis.The future of bioprinted models of thrombosis lies in the integration of patient-specific data,real-time monitoring technologies,and advanced microfluidic platforms,paving the way for personalized medicine and targeted interventions.As the field of bioprinting continues to evolve,these advanced vascular models are expected to play an increasingly important role in unraveling the complexities of thrombosis and improving patient outcomes.The continued advancements in bioprinting technologies and the collaboration between researchers from various disciplines hold great promise for revolutionizing the field of thrombosis research.
基金supported by the National Health and Medical Research Council(NHMRC)of Australia(APP2003904-L.A.J.)NSW Cardiovascular Capacity Building Program(Early-Mid Career Researcher Grant-L.A.J.,P.Q.and Z.W.)+12 种基金MRFF Cardiovascular Health Mission Grants(MRF2016165-L.A.J.)MRF2023977-L.A.J.,and MRFF Early-to-Mid Career Researchers Grant(MRF2028865-L.A.J.)NSW Government Boosting Business Innovation Program(BBIP)International Stream(L.A.J.)National Heart Foundation Vanguard Grant(106979-L.A.J.)University of Sydney External Research Collaboration Seed Fund(L.A.J.and Z.W.)Lining Arnold Ju is a Snow Medical Research Foundation Fellow(2022SF176)a National Heart Foundation Future Leader Fellow Level 2(105863)Y.C.Z.is a NHMRC PhD Scholar(GNT2022247-Y.C.Z)a National Heart Foundation PhD Scholar(106879)National Health and Medical Research Council(Australia)Investigator Emerging Leadership 1 grant(GNT2018376)Heart foundation future leader fellowship with Paul Korner Award(106780)McCusker Charitable Foundation.
文摘Addressing the pressing demand for rapid and inexpensive coagulation testing in cardiovascular care,this study introduces a novel application of repurposed COVID-19 rapid antigen tests(RATs)as paper-based lateral flow assays(LFAs)combined with machine learning for coagulation status evaluation.By further developing a mobile app prototype,we present a platform that enables clinicians to perform immediate and accurate anticoagulant dosing adjustments using existing post-pandemic resources.Our proof-of-concept employs a random forest machine learning classifier to interpret image feature variations on RAT NC membrane,correlating red blood cell(RBC)wicked diffusion distance in recalcified citrated whole blood with changes in coagulative viscosity,easily interpreted.Enhanced by confocal imaging studies of paper microfluidics,our approach provides insights into the mechanisms dissecting coagulation components,achieving high classification precision,recall,and F1-scores.The inverse relationship between RBC wicked diffusion distance and enoxaparin concentration paves the way for machine learning to inform real-time dose prescription adjustments,aligning with individual patient profiles to optimize therapeutic outcomes.This study not only demonstrates the potential of leveraging surplus RATs for coagulation management but also exemplifies a cost-effective,rapid,and smart strategy to enhance clinical decision-making in the post-pandemic era.
