Following injury in central nervous system（CNS）,there are pathological changes in the injured region,which include neuronal death,axonal damage and demyelination,inflammatory response and activation of glial cells.T...Following injury in central nervous system（CNS）,there are pathological changes in the injured region,which include neuronal death,axonal damage and demyelination,inflammatory response and activation of glial cells.The proliferation of a large number of astrocytes results in the formation of glial scar.展开更多
Diseases and disorders associated with nervous system such as injuries by trauma and neurodegeneration are shown to be one of the most serious problems in medicine, requiring innovative strategies to trigger and enhan...Diseases and disorders associated with nervous system such as injuries by trauma and neurodegeneration are shown to be one of the most serious problems in medicine, requiring innovative strategies to trigger and enhance the nerve regeneration. Tissue engineering aims to provide a highly biomimetic environment by using a combination of cells, materials and suitable biological cues, by which the lost body part may be regenerated or even fully rebuilt. Electrospinning, being able to produce extracellular matrix （ECM）-like nanostructures with great flexibility in design and choice of materials, have demonstrated their great po- tential for fabrication of nerve tissue engineered scaffolds. The review here begins with a brief description of the anatomy of native nervous system, which provides basic knowledge and ideas for the design of nerve tissue scaffolds, followed by five main parts in the design of electrospun nerve tissue engineered scaffolds including materials selection, structural design, in vitro bioreactor, functionalization and cellular support. Performances of biomimetic electrospun nanofibrous nerve implant devices are also reviewed. Finally, future directions for advanced electrospun nerve tissue engineered scaffolds are discussed.展开更多
The harsh local micro-environment following spinal cord injury(SCI)remains a great challenge for neural regeneration.Local reconstitution of a favorable micro-environment by biocompatible scaffolds with desirable func...The harsh local micro-environment following spinal cord injury(SCI)remains a great challenge for neural regeneration.Local reconstitution of a favorable micro-environment by biocompatible scaffolds with desirable functions has thus been an area of concern.Herein,a hybrid hydrogel was developed using Fmoc-grafted chitosan(FC)and Fmoc peptide(FI).Dynamic reversibleπ-πstacking interactions of the fluorenyl rings enabled the FC/FI hybrid hydrogel to exhibit excellent injectable and self-healing properties,as characterized by visual appearances and rheological tests.Furthermore,the FC/FI hybrid hydrogel showed a slow and persistent release of curcumin(Cur),which was named as FC/FI-Cur hydrogel.In vitro studies confirmed that with the support of FC/FI-Cur hydrogel,neurite outgrowth was promoted,and Schwann cell(SC)migration away from dorsal root ganglia(DRG)spheres with enhanced myelination was substantiated.The FC/FI-Cur hydrogel well reassembled extracellular matrix at the lesion site of rat spinal cord and exerted outstanding effects in modulating local inflammatory reaction by regulating the phenotypes of infiltrated inflammatory cells.In addition,endogenous SCs were recruited in the FC/FI-Cur graft and participated in the remyelination process of the regenerated nerves.These outcomes favored functional recovery,as evidenced by improved hind limbs movement and enhanced electrophysiological properties.Thus,our study not only advanced the development of multifunctional hydrogels but also provided insights into comprehensive approaches for SCI repair.展开更多
Peripheral nerves are fragile and easily damaged,usually resulting in nervous tissue loss,motor and sensory function loss.Advances in neuroscience and engineering have been significantly contributing to bridge the dam...Peripheral nerves are fragile and easily damaged,usually resulting in nervous tissue loss,motor and sensory function loss.Advances in neuroscience and engineering have been significantly contributing to bridge the damage nerve and create permissive environment for axonal regrowth across lesions.We have successfully designed two self-assembling peptides by modifying RADA 16-I with two functional motifs IKVAV and RGD.Nanofiber hydrogel formed when combing the two neutral solutions together,defined as RADA 16-Mix that overcomes the main drawback of RADA16-I associated with low pH.In the present study,we transplanted the RADA 16-Mix hydrogel into the transected rat sciatic nerve gap and effect on axonal regeneration was examined and compared with the traditional RADA16-I hydrogel.The regenerated nerves were found to grow along the walls of the large cavities formed in the graft of RADA16-I hydrogel,while the nerves grew into the RADA 16-Mix hydrogel toward distal position.RADA 16-Mix hydrogel induced more axons regeneration and Schwann cells immigration than RADA16-I hydrogel,resulting in better functional recovery as determined by the gait-stance duration percentage and the formation of new neuromuscular junction structures.Therefore,our results indicated that the functional SAP RADA16-Mix nanofibrous hydrogel provided a better environment for peripheral nerve regeneration than RADA16-I hydrogel and could be potentially used in peripheral nerve injury repair.展开更多
基金supported by National Basic Research Program of China(973 Program,2014CB542205)Hong Kong RGC grant+2 种基金Hong Kong Health and Medical Research Fundfoundation for Distinguished Young Talents in Higher Education of Guangdong(Yq2013023)the Leading Talents of Guangdong Province(87014002)
文摘Following injury in central nervous system（CNS）,there are pathological changes in the injured region,which include neuronal death,axonal damage and demyelination,inflammatory response and activation of glial cells.The proliferation of a large number of astrocytes results in the formation of glial scar.
文摘Diseases and disorders associated with nervous system such as injuries by trauma and neurodegeneration are shown to be one of the most serious problems in medicine, requiring innovative strategies to trigger and enhance the nerve regeneration. Tissue engineering aims to provide a highly biomimetic environment by using a combination of cells, materials and suitable biological cues, by which the lost body part may be regenerated or even fully rebuilt. Electrospinning, being able to produce extracellular matrix （ECM）-like nanostructures with great flexibility in design and choice of materials, have demonstrated their great po- tential for fabrication of nerve tissue engineered scaffolds. The review here begins with a brief description of the anatomy of native nervous system, which provides basic knowledge and ideas for the design of nerve tissue scaffolds, followed by five main parts in the design of electrospun nerve tissue engineered scaffolds including materials selection, structural design, in vitro bioreactor, functionalization and cellular support. Performances of biomimetic electrospun nanofibrous nerve implant devices are also reviewed. Finally, future directions for advanced electrospun nerve tissue engineered scaffolds are discussed.
基金This work was supported by the National Natural Science Foundation of China(31870964,32071354)Natural Science Foundation of Guangdong Province(2018A030313858)+1 种基金Guangzhou People’s Livelihood Science and Technology Tackling Project(201903010095)the Fundamental Research Funds for the Central Universities to Sun Yat-sen University.
文摘The harsh local micro-environment following spinal cord injury(SCI)remains a great challenge for neural regeneration.Local reconstitution of a favorable micro-environment by biocompatible scaffolds with desirable functions has thus been an area of concern.Herein,a hybrid hydrogel was developed using Fmoc-grafted chitosan(FC)and Fmoc peptide(FI).Dynamic reversibleπ-πstacking interactions of the fluorenyl rings enabled the FC/FI hybrid hydrogel to exhibit excellent injectable and self-healing properties,as characterized by visual appearances and rheological tests.Furthermore,the FC/FI hybrid hydrogel showed a slow and persistent release of curcumin(Cur),which was named as FC/FI-Cur hydrogel.In vitro studies confirmed that with the support of FC/FI-Cur hydrogel,neurite outgrowth was promoted,and Schwann cell(SC)migration away from dorsal root ganglia(DRG)spheres with enhanced myelination was substantiated.The FC/FI-Cur hydrogel well reassembled extracellular matrix at the lesion site of rat spinal cord and exerted outstanding effects in modulating local inflammatory reaction by regulating the phenotypes of infiltrated inflammatory cells.In addition,endogenous SCs were recruited in the FC/FI-Cur graft and participated in the remyelination process of the regenerated nerves.These outcomes favored functional recovery,as evidenced by improved hind limbs movement and enhanced electrophysiological properties.Thus,our study not only advanced the development of multifunctional hydrogels but also provided insights into comprehensive approaches for SCI repair.
基金The authors thank for funding supports from the National Program on Key Basic Research Project(973 Program,2014CB542205)Hong Kong RGC grant(17124514)+5 种基金Foundation for Distinguished Young Talents in Higher Education of Guangdong(Yq2013023)Pearl River Nova Program of Guangzhou(2014J2200001)China Postdoctoral Science Foundation(2013M540684)the Leading Talents of Guangdong Province(87014002)National Natural Science Foundation of China(51103062)The authors wish to acknowledge the support from the Hong Kong Scholars Program(XJ2012024).
文摘Peripheral nerves are fragile and easily damaged,usually resulting in nervous tissue loss,motor and sensory function loss.Advances in neuroscience and engineering have been significantly contributing to bridge the damage nerve and create permissive environment for axonal regrowth across lesions.We have successfully designed two self-assembling peptides by modifying RADA 16-I with two functional motifs IKVAV and RGD.Nanofiber hydrogel formed when combing the two neutral solutions together,defined as RADA 16-Mix that overcomes the main drawback of RADA16-I associated with low pH.In the present study,we transplanted the RADA 16-Mix hydrogel into the transected rat sciatic nerve gap and effect on axonal regeneration was examined and compared with the traditional RADA16-I hydrogel.The regenerated nerves were found to grow along the walls of the large cavities formed in the graft of RADA16-I hydrogel,while the nerves grew into the RADA 16-Mix hydrogel toward distal position.RADA 16-Mix hydrogel induced more axons regeneration and Schwann cells immigration than RADA16-I hydrogel,resulting in better functional recovery as determined by the gait-stance duration percentage and the formation of new neuromuscular junction structures.Therefore,our results indicated that the functional SAP RADA16-Mix nanofibrous hydrogel provided a better environment for peripheral nerve regeneration than RADA16-I hydrogel and could be potentially used in peripheral nerve injury repair.
