Due to the limited effects of current treatments on brain repair and regeneration,stroke continues to be the predominant cause of death and long-term disability on a global scale.In recent years,hydrogel-based biomate...Due to the limited effects of current treatments on brain repair and regeneration,stroke continues to be the predominant cause of death and long-term disability on a global scale.In recent years,hydrogel-based biomaterials combined with stem cells and extracellular vesicles have emerged as promising new treatments to improve brain regeneration after stroke.However,the clinical translation of hydrogel-based biomaterials for the treatment of brain injury is still far from satisfactory.In this review,we first summarise the present status of stroke-related clinical treatments and the advantages provided by hydrogel-based materials in combination with stem cells and extracellular vesicles in preclinical studies.We then focus on the possible causes of the gap between preclinical studies and clinical translation of hydrogel-based biomaterials from the perspective of biocompatibility and safety,the choices of preclinical models,the lack of clinical noninvasive imaging methods,standardisation and quality control,manufacturing scalability,and regulatory compliance.With the progress in the abovementioned areas,we believe that the clinical translation of hydrogel-based biomaterials will greatly improve brain regeneration after stroke and that this improvement will be realised by the general public in the near future.展开更多
The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system(CNS)injury.Maintaining brain immune homeostasis is crucial for restoring neuro...The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system(CNS)injury.Maintaining brain immune homeostasis is crucial for restoring neurovascular function.In this study,an interactive bridge was developed via an immunomodulatory hydrogel microsphere to link the interaction network between microglia and the neurovascular unit,thereby precisely regulating immune-neurovascular crosstalk and achieving neural function recovery.This immunomodulatory crosstalk microsphere(MP/RIL4)was composed of microglia-targeted RAP12 peptide-modified interleukin-4(IL-4)nanoparticles and boronic ester-functionalized hydrogel using biotin-avidin reaction and air-microfluidic techniques.We confirmed that the immunomodulatory microspheres reduced the expression of pro-inflammatory factors including IL-1β,iNOS,and CD86,while upregulating levels of anti-inflammatory factors such as IL-10,Arg-1,and CD206 in microglia.In addition,injection of the MP/RIL4 significantly mitigated brain atrophy volume in a mouse model of ischemic stroke,promoted neurobehavioral recovery,and enhanced the crosstalk between immune cells and the neurovascular unit,thus increasing angiogenesis and neurogenesis of stroke mice.In summary,the immunomodulatory microspheres,capable of orchestrating the interaction between immune cells and neurovascular unit,hold considerable therapeutic potential for ischemic stroke and other CNS diseases.展开更多
基金the National Key R&D Program of China,No.2019YFA0112000(to YT)the National Natural Science Foundation of China(NSFC),Nos.82071284(to YT),82371307(to YT),82172529(to JW),32060184(to HM)+4 种基金Natural Science Foundation of Shanghai,No.21ZR1451700(to HL)Young Leading Scientists Cultivation Plan supported by Shanghai Municipal Education Commission,No.ZXWH1082101(to YT)Interdisciplinary Program of Shanghai Jiao Tong University,No.ZH2018QNA16(to YT)Key Projects of the National Center for Translational Medicine SUITM-202306(to YT)and Joint Special Funds for the Department of Science and Technology of Yunnan Province-Kunming Medical University,No.202101AY070001-044(to HM).
文摘Due to the limited effects of current treatments on brain repair and regeneration,stroke continues to be the predominant cause of death and long-term disability on a global scale.In recent years,hydrogel-based biomaterials combined with stem cells and extracellular vesicles have emerged as promising new treatments to improve brain regeneration after stroke.However,the clinical translation of hydrogel-based biomaterials for the treatment of brain injury is still far from satisfactory.In this review,we first summarise the present status of stroke-related clinical treatments and the advantages provided by hydrogel-based materials in combination with stem cells and extracellular vesicles in preclinical studies.We then focus on the possible causes of the gap between preclinical studies and clinical translation of hydrogel-based biomaterials from the perspective of biocompatibility and safety,the choices of preclinical models,the lack of clinical noninvasive imaging methods,standardisation and quality control,manufacturing scalability,and regulatory compliance.With the progress in the abovementioned areas,we believe that the clinical translation of hydrogel-based biomaterials will greatly improve brain regeneration after stroke and that this improvement will be realised by the general public in the near future.
基金supported by National Natural Science Foundation of China 81930051(WC)“Chenguang Program”(22CGA16)supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission,the National Key R&D Program of China#2019YFA0112000(YT)+4 种基金National Natural Science Foundation of China 82071284(YT),82371307(YT),82372120(HR)Shanghai Rising-Star Program(21QA1405200,YT)Young Leading Scientists Cultivation Plan supported by Shanghai Municipal Education Commission(ZXWH1082101,YT)“Two Hundred Talent”Program supported by Shanghai Jiao Tong University School of Medicine(20240701,HR)the Fundamental Research Funds for the Central Universities(YG2023ZD02,YT).
文摘The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system(CNS)injury.Maintaining brain immune homeostasis is crucial for restoring neurovascular function.In this study,an interactive bridge was developed via an immunomodulatory hydrogel microsphere to link the interaction network between microglia and the neurovascular unit,thereby precisely regulating immune-neurovascular crosstalk and achieving neural function recovery.This immunomodulatory crosstalk microsphere(MP/RIL4)was composed of microglia-targeted RAP12 peptide-modified interleukin-4(IL-4)nanoparticles and boronic ester-functionalized hydrogel using biotin-avidin reaction and air-microfluidic techniques.We confirmed that the immunomodulatory microspheres reduced the expression of pro-inflammatory factors including IL-1β,iNOS,and CD86,while upregulating levels of anti-inflammatory factors such as IL-10,Arg-1,and CD206 in microglia.In addition,injection of the MP/RIL4 significantly mitigated brain atrophy volume in a mouse model of ischemic stroke,promoted neurobehavioral recovery,and enhanced the crosstalk between immune cells and the neurovascular unit,thus increasing angiogenesis and neurogenesis of stroke mice.In summary,the immunomodulatory microspheres,capable of orchestrating the interaction between immune cells and neurovascular unit,hold considerable therapeutic potential for ischemic stroke and other CNS diseases.
