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
Small-diameter vascular grafts fabricated from synthetic biodegradable polymers exhibit beneficial mechanical properties but often face poor regenerative potential.Different tissue engineering approaches have been emp...Small-diameter vascular grafts fabricated from synthetic biodegradable polymers exhibit beneficial mechanical properties but often face poor regenerative potential.Different tissue engineering approaches have been employed to improve tissue regeneration in vascular grafts,but there remains a requirement for a new generation of synthetic grafts that can orchestrate the host response to achieve robust vascular regeneration.Vascular stem/progenitor cells(SPCs)are mostly found in quiescent niches but can be activated in response to injury and participate in endothelium and smooth muscle regeneration during neo-artery formation.Here,we developed a functional vascular graft by surface immobilization of stem cell antigen-1(Sca-1)antibody on an electrospun poly(ε-caprolactone)graft(PCL-Sca-1 Ab).PCL-Sca-1 Ab promoted capture and retainment of Sca-1+SPCs in vitro.In rat abdominal aorta replacement models,PCL-Sca-1 Ab stimulated in vivo recruitment of Sca-1+SPCs,and drove SPCs differentiation towards vascular cell lineages.The origin of infiltrated Sca-1+SPCs was further investigated using a bone marrow transplantation mouse model,which revealed that Sca-1+SPCs originating from the resident tissues and bone marrow contributed to rapid vascular regeneration of vascular grafts.Our data indicated that PCL-Sca-1 Ab vascular grafts may serve as a useful strategy to develop next generation cell-free vascular grafts.展开更多
Vascular regeneration and patency maintenance,without anticoagulant administration,represent key developmental trends to enhance small-diameter vascular grafts(SDVG)performance.In vivo engineered autologous biotubes h...Vascular regeneration and patency maintenance,without anticoagulant administration,represent key developmental trends to enhance small-diameter vascular grafts(SDVG)performance.In vivo engineered autologous biotubes have emerged as SDVG candidates with pro-regenerative properties.However,mechanical failure coupled with thrombus formation hinder translational prospects of biotubes as SDVGs.Previously fabricated poly(ε-caprolactone)skeleton-reinforced biotubes(PBs)circumvented mechanical issues and achieved vascular regeneration,but orally administered anticoagulants were required.Here,highly efficient and biocompatible functional modifications were introduced to living cells on PB lumens.The 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(DMPE)-PEG-conjugated anti-coagulant bivalirudin(DPB)and DMPE-PEG-conjugated endothelial progenitor cell(EPC)-binding TPS-peptide(DPT)modifications possessed functionality conducive to promoting vascular graft patency.Co-modification of DPB and DPT swiftly attained luminal saturation without influencing cell viability.DPB repellent of non-specific proteins,DPB inhibition of thrombus formation,and DPB protection against functional masking of DPT’s EPC-capture by blood components,which promoted patency and rapid endothelialization in rat and canine artery implantation models without anticoagulant administration.This strategy offers a safe,facile,and fast technical approach to convey additional functionalization to living cells within tissue-engineered constructs.展开更多
Translation of exosome-based therapies to pharmaceutical use is hindered by difficulties in large-scale and cost-effective production of clinical-grade exosomes.The rational design of nanovesicles that mimic the funct...Translation of exosome-based therapies to pharmaceutical use is hindered by difficulties in large-scale and cost-effective production of clinical-grade exosomes.The rational design of nanovesicles that mimic the functionalities and physicochemical properties of exosomes may circumvent these issues.In this study,membranes and secretome from efficacy-potentiated mesenchymal stem cells(MSCs)were developed into size-controllable nanovesicles(Meseomes).MSCs were primed with interferon-y(IFNy)and tumor necrosis factor-a(TNFa),harvested,and exosome-mimicking Meseomes were subsequently synthesized via one-step extrusion.Meseomes demonstrated significant enhancement of pro-angiogenic,pro-proliferative,antiinflammatory,and anti-fibrotic effects on endothelial cells,macrophages,and hepatic stellate cells in vitro.Meseomes from primed MSCs benefited from an enrichment of bioactive and therapeutic molecules compared to nanovesicles from unprimed MSCs,as validated by liquid chromatography-mass spectrometry(LC-MS)proteomic analysis.Systemic administration of Meseomes to acute liver injury models resulted in the recovery of liver function,attenuated tissue necrosis.Further assessment of locally administered Meseomes in acute hindlimb ischemia models resulted in the salvage of the majority of the ischemic hindlimb(>80%),which was due to enhanced angiogenesis and M2 macrophage polarization.The versatility and therapeutic efficacy of our developed acellular Meseomes offer an appealing alternative to traditional cell or exosome therapies for regenerative and translational medicine.展开更多
Erratum to Nano Research 2022,15(2):1680–1690 https://doi.org/10.1007/s12274-021-3868-z The article Exosome-mimicking nanovesicles derived from efficacy-potentiated stem cell membrane and secretome for regeneration o...Erratum to Nano Research 2022,15(2):1680–1690 https://doi.org/10.1007/s12274-021-3868-z The article Exosome-mimicking nanovesicles derived from efficacy-potentiated stem cell membrane and secretome for regeneration of injured tissue,written by Chunxiao Qi et al.,was erroneously published with duplicated microscopy panels in Fig.3(d).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 grants from the National Natural Science Foundation of China(Nos.81925021,82050410449,81921004 and 81871500)and Science&Technology Project of Tianjin of China(No.18JCJQJC46900).
文摘Small-diameter vascular grafts fabricated from synthetic biodegradable polymers exhibit beneficial mechanical properties but often face poor regenerative potential.Different tissue engineering approaches have been employed to improve tissue regeneration in vascular grafts,but there remains a requirement for a new generation of synthetic grafts that can orchestrate the host response to achieve robust vascular regeneration.Vascular stem/progenitor cells(SPCs)are mostly found in quiescent niches but can be activated in response to injury and participate in endothelium and smooth muscle regeneration during neo-artery formation.Here,we developed a functional vascular graft by surface immobilization of stem cell antigen-1(Sca-1)antibody on an electrospun poly(ε-caprolactone)graft(PCL-Sca-1 Ab).PCL-Sca-1 Ab promoted capture and retainment of Sca-1+SPCs in vitro.In rat abdominal aorta replacement models,PCL-Sca-1 Ab stimulated in vivo recruitment of Sca-1+SPCs,and drove SPCs differentiation towards vascular cell lineages.The origin of infiltrated Sca-1+SPCs was further investigated using a bone marrow transplantation mouse model,which revealed that Sca-1+SPCs originating from the resident tissues and bone marrow contributed to rapid vascular regeneration of vascular grafts.Our data indicated that PCL-Sca-1 Ab vascular grafts may serve as a useful strategy to develop next generation cell-free vascular grafts.
基金supported by the National Natural Science Foundation of China(NSFC)projects 81921004(D.K.),82127808(D.K.),32222043(K.W.),82250610231(A.C.M.)National Key R&D Program of China 2022YFA1105102(K.W.)+3 种基金Tianjin Natural Science Foundation 20JCYBJC01150(K.W.)Tianjin Natural Science Foundation 18JCZDJC37600(K.W.)NCC Fund NCC2020PY18(K.W.)Tianjin"Project+Team"Key Training Foundation XC202035(K.W.).
文摘Vascular regeneration and patency maintenance,without anticoagulant administration,represent key developmental trends to enhance small-diameter vascular grafts(SDVG)performance.In vivo engineered autologous biotubes have emerged as SDVG candidates with pro-regenerative properties.However,mechanical failure coupled with thrombus formation hinder translational prospects of biotubes as SDVGs.Previously fabricated poly(ε-caprolactone)skeleton-reinforced biotubes(PBs)circumvented mechanical issues and achieved vascular regeneration,but orally administered anticoagulants were required.Here,highly efficient and biocompatible functional modifications were introduced to living cells on PB lumens.The 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(DMPE)-PEG-conjugated anti-coagulant bivalirudin(DPB)and DMPE-PEG-conjugated endothelial progenitor cell(EPC)-binding TPS-peptide(DPT)modifications possessed functionality conducive to promoting vascular graft patency.Co-modification of DPB and DPT swiftly attained luminal saturation without influencing cell viability.DPB repellent of non-specific proteins,DPB inhibition of thrombus formation,and DPB protection against functional masking of DPT’s EPC-capture by blood components,which promoted patency and rapid endothelialization in rat and canine artery implantation models without anticoagulant administration.This strategy offers a safe,facile,and fast technical approach to convey additional functionalization to living cells within tissue-engineered constructs.
基金supported by the National Natural Science Foundation of China(NSFC)projects(Nos.81901905,81830060,and 82050410449)China Postdoctoral Science Foundation(No.2019M660989).
文摘Translation of exosome-based therapies to pharmaceutical use is hindered by difficulties in large-scale and cost-effective production of clinical-grade exosomes.The rational design of nanovesicles that mimic the functionalities and physicochemical properties of exosomes may circumvent these issues.In this study,membranes and secretome from efficacy-potentiated mesenchymal stem cells(MSCs)were developed into size-controllable nanovesicles(Meseomes).MSCs were primed with interferon-y(IFNy)and tumor necrosis factor-a(TNFa),harvested,and exosome-mimicking Meseomes were subsequently synthesized via one-step extrusion.Meseomes demonstrated significant enhancement of pro-angiogenic,pro-proliferative,antiinflammatory,and anti-fibrotic effects on endothelial cells,macrophages,and hepatic stellate cells in vitro.Meseomes from primed MSCs benefited from an enrichment of bioactive and therapeutic molecules compared to nanovesicles from unprimed MSCs,as validated by liquid chromatography-mass spectrometry(LC-MS)proteomic analysis.Systemic administration of Meseomes to acute liver injury models resulted in the recovery of liver function,attenuated tissue necrosis.Further assessment of locally administered Meseomes in acute hindlimb ischemia models resulted in the salvage of the majority of the ischemic hindlimb(>80%),which was due to enhanced angiogenesis and M2 macrophage polarization.The versatility and therapeutic efficacy of our developed acellular Meseomes offer an appealing alternative to traditional cell or exosome therapies for regenerative and translational medicine.
文摘Erratum to Nano Research 2022,15(2):1680–1690 https://doi.org/10.1007/s12274-021-3868-z The article Exosome-mimicking nanovesicles derived from efficacy-potentiated stem cell membrane and secretome for regeneration of injured tissue,written by Chunxiao Qi et al.,was erroneously published with duplicated microscopy panels in Fig.3(d).
