Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord inj...Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen＇s method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.展开更多
Tissue engineering and regenerative medicine is a new interdisciplinary subject integrating life science,material science,engineering technology,and clinical medicine.Over the last ten years,significant advancements h...Tissue engineering and regenerative medicine is a new interdisciplinary subject integrating life science,material science,engineering technology,and clinical medicine.Over the last ten years,significant advancements have been achieved in the study of biomaterials and tissue engineering.Progress in the field of tissue engineering and regenerative medicine can result in optimal tissue regeneration and effective functional reconstruction.Spinal cord injury(SCI)is the most severe complication of spinal trauma and frequently results in significant functional impairments in the lower extremities of the affected segment.Repair of SCI is a medical challenge worldwide.Advancements in tissue engineering theory and technology offer fresh opportunities for addressing SCI,as well as providing new strategies and methodologies to tackle the challenges associated with repairing and reconstructing spinal cord function.This article provides an overview of the latest developments in tissue engineering and SCI repair,focusing on biomaterials,cells,and active factors.It also introduces nine key components related to SCI and proposes innovative approaches for repairing and functionally reconstructing the injured spinal cord.展开更多
Background:The extracellular matrix(ECM)provides essential physical support and biochemical cues for diverse biological activities,including tissue remodelling and regeneration,and thus is commonly applied in the cons...Background:The extracellular matrix(ECM)provides essential physical support and biochemical cues for diverse biological activities,including tissue remodelling and regeneration,and thus is commonly applied in the construction of artificial peripheral nerve grafts.Nevertheless,the specific functions of essential peripheral nerve ECM components have not been fully determined.Our research aimed to differentially represent the neural activities of main components of ECM on peripheral nerve regeneration.Methods:Schwann cells from sciatic nerves and neurons from dorsal root ganglia were isolated and cultured in vitro.The cells were seeded onto noncoated dishes,Matrigel-coated dishes,and dishes coated with the four major ECM components fibronectin,laminin,collagen I,and collagen IV.The effects of these ECM components on Schwann cell proliferation were determined via methylthiazolyldiphenyl-tetrazolium bromide(MTT),Cell Counting Kit-8,and 5-ethynyl-2’-deoxyuridine(EdU)assays,whereas their effects on cell migration were determined via wound healing and live-cell imaging.Neurite growth in neurons cultured on different ECM components was observed.Furthermore,the two types of collagen were incorporated into chitosan artificial nerves and used to repair sciatic nerve defects in rats.Immunofluorescence analysis and a behavioural assessment,including gait,electrophysiology,and target muscle analysis,were conducted.Results:ECM components,especially collagen I,stimulated the DNA synthesis and movement of Schwann cells.Direct measurement of the neurite lengths of neurons cultured on ECM components further revealed the beneficial effects of ECM components on neurite outgrowth.Injection of collagen I into chitosan and poly(lactic-co-glycolic acid)artificial nerves demonstrated that collagen I facilitated axon regeneration and functional recovery after nerve defect repair by stimulating the migration of Schwann cells and the formation of new blood vessels.In contrast,collagen IV recruited excess fibroblasts and inflammatory macrophages and thus had disadvantageous effects on nerve regeneration.Conclusions:These findings reveal the modulatory effects of specific ECM components on cell populations of peripheral nerves,reveal the contributing roles of collagen I in microenvironment construction and axon regeneration,and highlight the use of collagen I for the healing of injured peripheral nerves.展开更多
Peripheral nerve injury is a complex and challenging medical condition due to the limited ability of nerves to regenerate, resulting in the loss of both sensory and motor function. Hydrogels have emerged as a promisin...Peripheral nerve injury is a complex and challenging medical condition due to the limited ability of nerves to regenerate, resulting in the loss of both sensory and motor function. Hydrogels have emerged as a promising biomaterial for promoting peripheral nerve regeneration, while conventional hydrogels are generally unable to support endogenous cell infiltration due to limited network dynamics, thereby compromising the therapeutic outcomes. Herein, we present a cell adaptable hydrogel containing a tissue-mimetic silk fibroin network and a dynamically crosslinked bisphosphonated-alginate network. The dynamic network of this hydrogel can respond to cell-generated forces to undergo the cell-mediated reorganization, thereby effectively facilitating the rapid infiltration of Schwann cells and macrophages, as well as the ingrowth of axons. We further show that the magnesium ions released from the hydrogel not only promote neurite outgrowth but also regulate the polarization of macrophages in a sequential manner, contributing to the formation of a regenerative microenvironment. Therefore, this hydrogel effectively prevents muscle atrophy and promotes the regeneration and functional recovery of nerve defects of up to 10 mm within 8 weeks. The findings from this study demonstrate that adaptable hydrogels are promising inductive biomaterials for enhancing the therapeutic outcomes of peripheral nerve injury treatments.展开更多
文摘Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen＇s method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.
基金supported by grants from the National Natural Science Foundation of China(92368207)the Chinese Academy of Engineering(2023-SBZD-11)the Natural Science Foundation of Jiangsu Province(BK20232023).
文摘Tissue engineering and regenerative medicine is a new interdisciplinary subject integrating life science,material science,engineering technology,and clinical medicine.Over the last ten years,significant advancements have been achieved in the study of biomaterials and tissue engineering.Progress in the field of tissue engineering and regenerative medicine can result in optimal tissue regeneration and effective functional reconstruction.Spinal cord injury(SCI)is the most severe complication of spinal trauma and frequently results in significant functional impairments in the lower extremities of the affected segment.Repair of SCI is a medical challenge worldwide.Advancements in tissue engineering theory and technology offer fresh opportunities for addressing SCI,as well as providing new strategies and methodologies to tackle the challenges associated with repairing and reconstructing spinal cord function.This article provides an overview of the latest developments in tissue engineering and SCI repair,focusing on biomaterials,cells,and active factors.It also introduces nine key components related to SCI and proposes innovative approaches for repairing and functionally reconstructing the injured spinal cord.
基金supported by grants from the National Key R&D Program of China(2022YFC24098002022YFC2409802)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_3381)+3 种基金the Natural Science Foundation of Jiangsu Province(BK20231338)Jiangsu Provincial Key Medical Center and Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Jiangsu College Students Innovation and Entrepreneurship Training Program(202310304120Y)the Science and Technology Plan Program of Nantong(MS2023050).
文摘Background:The extracellular matrix(ECM)provides essential physical support and biochemical cues for diverse biological activities,including tissue remodelling and regeneration,and thus is commonly applied in the construction of artificial peripheral nerve grafts.Nevertheless,the specific functions of essential peripheral nerve ECM components have not been fully determined.Our research aimed to differentially represent the neural activities of main components of ECM on peripheral nerve regeneration.Methods:Schwann cells from sciatic nerves and neurons from dorsal root ganglia were isolated and cultured in vitro.The cells were seeded onto noncoated dishes,Matrigel-coated dishes,and dishes coated with the four major ECM components fibronectin,laminin,collagen I,and collagen IV.The effects of these ECM components on Schwann cell proliferation were determined via methylthiazolyldiphenyl-tetrazolium bromide(MTT),Cell Counting Kit-8,and 5-ethynyl-2’-deoxyuridine(EdU)assays,whereas their effects on cell migration were determined via wound healing and live-cell imaging.Neurite growth in neurons cultured on different ECM components was observed.Furthermore,the two types of collagen were incorporated into chitosan artificial nerves and used to repair sciatic nerve defects in rats.Immunofluorescence analysis and a behavioural assessment,including gait,electrophysiology,and target muscle analysis,were conducted.Results:ECM components,especially collagen I,stimulated the DNA synthesis and movement of Schwann cells.Direct measurement of the neurite lengths of neurons cultured on ECM components further revealed the beneficial effects of ECM components on neurite outgrowth.Injection of collagen I into chitosan and poly(lactic-co-glycolic acid)artificial nerves demonstrated that collagen I facilitated axon regeneration and functional recovery after nerve defect repair by stimulating the migration of Schwann cells and the formation of new blood vessels.In contrast,collagen IV recruited excess fibroblasts and inflammatory macrophages and thus had disadvantageous effects on nerve regeneration.Conclusions:These findings reveal the modulatory effects of specific ECM components on cell populations of peripheral nerves,reveal the contributing roles of collagen I in microenvironment construction and axon regeneration,and highlight the use of collagen I for the healing of injured peripheral nerves.
基金supported by National Natural Science Foundation of China(32230057,32271385,32371400)Natural Science Foundation of Jiangsu Province(BK20231338)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(21KJA 430011).
文摘Peripheral nerve injury is a complex and challenging medical condition due to the limited ability of nerves to regenerate, resulting in the loss of both sensory and motor function. Hydrogels have emerged as a promising biomaterial for promoting peripheral nerve regeneration, while conventional hydrogels are generally unable to support endogenous cell infiltration due to limited network dynamics, thereby compromising the therapeutic outcomes. Herein, we present a cell adaptable hydrogel containing a tissue-mimetic silk fibroin network and a dynamically crosslinked bisphosphonated-alginate network. The dynamic network of this hydrogel can respond to cell-generated forces to undergo the cell-mediated reorganization, thereby effectively facilitating the rapid infiltration of Schwann cells and macrophages, as well as the ingrowth of axons. We further show that the magnesium ions released from the hydrogel not only promote neurite outgrowth but also regulate the polarization of macrophages in a sequential manner, contributing to the formation of a regenerative microenvironment. Therefore, this hydrogel effectively prevents muscle atrophy and promotes the regeneration and functional recovery of nerve defects of up to 10 mm within 8 weeks. The findings from this study demonstrate that adaptable hydrogels are promising inductive biomaterials for enhancing the therapeutic outcomes of peripheral nerve injury treatments.
