Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair.Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominen...Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair.Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominent donor-site complications.Instead,imitating the native neural microarchitecture using synthetic conduits is expected to offer an alternative strategy for improving nerve regeneration.Here,we designed nerve conduits composed of high-resolution anisotropic microfiber grid-cordes with randomly organized nanofiber sheaths to interrogate the positive effects of these biomimetic structures on peripheral nerve regeneration.Anisotropic microfiber-grids demonstrated the capacity to directionally guide Schwann cells and neurites.Nanofiber sheaths conveyed adequate elasticity and permeability,whilst exhibiting a barrier function against the infiltration of fibroblasts.We then used the composite nerve conduits bridge 30-mm long sciatic nerve defects in canine models.At 12 months post-implant,the morphometric and histological recovery,gait recovery,electrophysiological function,and degree of muscle atrophy were assessed.The newly regenerated nerve tissue that formed within the composite nerve conduits showed restored neurological functions that were superior compared to sheaths-only scaffolds and Neurolac nerve conduit controls.Our findings demonstrate the feasibility of using synthetic biophysical cues to effectively bridge long-gap peripheral nerve injuries and indicates the promising clinical application prospects of biomimetic composite nerve conduits.展开更多
The peripheral nervous system is able to regenerate after injury, and regeneration is associated with the expression of many genes and proteins. MicroRNAs are evolutionarily conserved, small, non-coding RNA molecules ...The peripheral nervous system is able to regenerate after injury, and regeneration is associated with the expression of many genes and proteins. MicroRNAs are evolutionarily conserved, small, non-coding RNA molecules that regulate gene expression at the level of translation. In this paper, we focus on the identification and functional annotation of novel microRNAs in the proximal sciatic nerve after rat sciatic nerve transection. Using Solexa sequencing, computational analysis, and quantitative reverse transcription PCR verification, we identified 98 novel microRNAs expressed on days 0, 1, 4, 7, and 14 after nerve transection. Furthermore, we predicted the target genes of these microRNAs and analyzed the biological processes in which they were involved. The identified biological processes were consistent with the known time-frame of peripheral nerve injury and repair. Our data provide an important resource for further study of the role and regulation of microRNAs in peripheral nerve injury and regeneration.展开更多
To find a promising alternative to neurons or schwann cells (SCs) for peripheral nerve repair applications,this study sought to isolate stem cells from fetal rat dorsal root ganglion (DRG) explants.Molecular expressio...To find a promising alternative to neurons or schwann cells (SCs) for peripheral nerve repair applications,this study sought to isolate stem cells from fetal rat dorsal root ganglion (DRG) explants.Molecular expression analysis confirmed neural stem cell characteristics of DRG-derived neurospheres in terms of expressing neural stem cell-specific genes and a set of well-defined genes related to stem cell niches and glial fate decision.Under the influence of neurotrophic factors,bFGF and NGF,the neurospheres gave rise to neurofilament-expressing neurons and S100-expressing Schwann cell-like cells by different pathways.This study suggests that a subpopulation of stem cells that reside in DRGs is the progenitor of neurons and glia,which could directly induce the differentiation toward neurons,or SCs.展开更多
Peripheral nerve functional recovery after nerve injury generally requires multiple growth factors by synergistic effect.However,the optical combination of multiple synergistic growth factors for axonal regeneration h...Peripheral nerve functional recovery after nerve injury generally requires multiple growth factors by synergistic effect.However,the optical combination of multiple synergistic growth factors for axonal regeneration has been scarcely considered up to now.Meanwhile,the use of growth factors in promoting nerve regeneration was limited by its short biological half-life in vivo,its vulnerability to structure disruption or hydrolyzation,leading to loss of bioactivity.Herein,a novel polymeric nanoparticle delivery system composed of heparin andε-poly-L-lysine(PL)was prepared for control release of nerve growth factor(NGF)and basic fibroblast growth factor(bFGF).The nanoparticles were synthesized by polyelectrolyte complexation in aqueous solution at room temperature,followed by cross-linking with biological genipin.The obtained nanoparticles had a spherical shape,with a mean diameter of about 246 nm,and high growth factors encapsulation efficiency as well as good stability.NGF and bFGF were encapsulated in the nanoparticles and showed a continuous and slow release behavior in vitro.The bioactivities of the released growth factors were evaluated,and exhibited the synergistic effect.The controlled release of the dual synergistic growth factors would improve the treatment of peripheral nerve injury to mimic the natural cellular microenvironments.展开更多
基金National Natural Science Foundation of China projects(81921004,D.K.)National Natural Science Foundation of China projects(32201122,X.D.)+3 种基金National Natural Science Foundation of China projects(82272156,M.Z.)China Postdoctoral Science Foundation(2022M711705 X.D.)Key Military Medical Project(No.BLB21J008,D.K.)Tianjin Natural Science Foundation(C100303 F M.).
文摘Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair.Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominent donor-site complications.Instead,imitating the native neural microarchitecture using synthetic conduits is expected to offer an alternative strategy for improving nerve regeneration.Here,we designed nerve conduits composed of high-resolution anisotropic microfiber grid-cordes with randomly organized nanofiber sheaths to interrogate the positive effects of these biomimetic structures on peripheral nerve regeneration.Anisotropic microfiber-grids demonstrated the capacity to directionally guide Schwann cells and neurites.Nanofiber sheaths conveyed adequate elasticity and permeability,whilst exhibiting a barrier function against the infiltration of fibroblasts.We then used the composite nerve conduits bridge 30-mm long sciatic nerve defects in canine models.At 12 months post-implant,the morphometric and histological recovery,gait recovery,electrophysiological function,and degree of muscle atrophy were assessed.The newly regenerated nerve tissue that formed within the composite nerve conduits showed restored neurological functions that were superior compared to sheaths-only scaffolds and Neurolac nerve conduit controls.Our findings demonstrate the feasibility of using synthetic biophysical cues to effectively bridge long-gap peripheral nerve injuries and indicates the promising clinical application prospects of biomimetic composite nerve conduits.
基金supported by the National High Technology Research and Development Program of China (Grant No. 2006AA02A128)the National Natural Science Foundation of China (Grant No. 30870811)+1 种基金the Jiangsu Provincial Natural Science Foundation (Grant No. BK2008010)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
文摘The peripheral nervous system is able to regenerate after injury, and regeneration is associated with the expression of many genes and proteins. MicroRNAs are evolutionarily conserved, small, non-coding RNA molecules that regulate gene expression at the level of translation. In this paper, we focus on the identification and functional annotation of novel microRNAs in the proximal sciatic nerve after rat sciatic nerve transection. Using Solexa sequencing, computational analysis, and quantitative reverse transcription PCR verification, we identified 98 novel microRNAs expressed on days 0, 1, 4, 7, and 14 after nerve transection. Furthermore, we predicted the target genes of these microRNAs and analyzed the biological processes in which they were involved. The identified biological processes were consistent with the known time-frame of peripheral nerve injury and repair. Our data provide an important resource for further study of the role and regulation of microRNAs in peripheral nerve injury and regeneration.
基金supported by the National High Technology Research and Development Program of China (Grant No. 2006AA02A128)the National Natural Science Foundation of China (Grant No. 30670667)the Natural Science Foundation of Jiangsu Province (Grant No. BK2008010)
文摘To find a promising alternative to neurons or schwann cells (SCs) for peripheral nerve repair applications,this study sought to isolate stem cells from fetal rat dorsal root ganglion (DRG) explants.Molecular expression analysis confirmed neural stem cell characteristics of DRG-derived neurospheres in terms of expressing neural stem cell-specific genes and a set of well-defined genes related to stem cell niches and glial fate decision.Under the influence of neurotrophic factors,bFGF and NGF,the neurospheres gave rise to neurofilament-expressing neurons and S100-expressing Schwann cell-like cells by different pathways.This study suggests that a subpopulation of stem cells that reside in DRGs is the progenitor of neurons and glia,which could directly induce the differentiation toward neurons,or SCs.
基金supported by the National High Technology Research and Development Program of China(2012AA020502)National Natural Science Foundation of China(81171457,81371687)+3 种基金Natural Science Foundation of Jiangsu Province of China(BK20130390)Natural Science Foundation of Nantong City(BK2012089)the Natural Science Research Program of Jiangsu Education Department(13KJB310014)the Priority of Academic Program Development of Jiangsu Higher Education Institutions and Natural Science Foundation of Nantong University(10Z014)
文摘Peripheral nerve functional recovery after nerve injury generally requires multiple growth factors by synergistic effect.However,the optical combination of multiple synergistic growth factors for axonal regeneration has been scarcely considered up to now.Meanwhile,the use of growth factors in promoting nerve regeneration was limited by its short biological half-life in vivo,its vulnerability to structure disruption or hydrolyzation,leading to loss of bioactivity.Herein,a novel polymeric nanoparticle delivery system composed of heparin andε-poly-L-lysine(PL)was prepared for control release of nerve growth factor(NGF)and basic fibroblast growth factor(bFGF).The nanoparticles were synthesized by polyelectrolyte complexation in aqueous solution at room temperature,followed by cross-linking with biological genipin.The obtained nanoparticles had a spherical shape,with a mean diameter of about 246 nm,and high growth factors encapsulation efficiency as well as good stability.NGF and bFGF were encapsulated in the nanoparticles and showed a continuous and slow release behavior in vitro.The bioactivities of the released growth factors were evaluated,and exhibited the synergistic effect.The controlled release of the dual synergistic growth factors would improve the treatment of peripheral nerve injury to mimic the natural cellular microenvironments.
