Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduit...Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.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
Cardiovascular diseases cause huge morbidity and mortality worldwide.Recently,vascular stents have been most frequently used to treat cardiovascular diseases thanks to their effectiveness at dilating blood vessels and...Cardiovascular diseases cause huge morbidity and mortality worldwide.Recently,vascular stents have been most frequently used to treat cardiovascular diseases thanks to their effectiveness at dilating blood vessels and main-taining the circulation of blood.However,stent expansion leads to endothelium injury posing thrombogenic and in-stent restenosis(ISR).In addition,the bioinertness and an acute lack of endothelium-like function on the surface of implanted vascular stents compromise their performance.Functional coatings of vascular stents to mimic endothelium-and extracellular matrix(ECM)-like functions could prevent thrombosis,inhibit the over-growth of smooth muscle cells(SMCs),and promote the rapid restoration of native endothelium,hence effec-tively suppressing stent-related complications.Noticeably,ECM-based coatings including a multitude of bioactive molecular,such as growth factors,heparin,hyaluronic acid(HA)and so on,have been proven to play important effects on regulating ECs/SMCs behavior and improving blood compatibility of stents.Additionally,nitric oxide(NO),which is fundamental to the endothelium-mediated anti-thrombogenesity,anti-intimal hyperplasia and anti-inflammation,has been leveraged to improve vascular stent functions.Therefore,this review will highlight different strategies and biological role of ECM and NO based functional coatings on vascular stent.Lastly,some potential important factors for stents development are suggested as well.展开更多
基金supported by the National Natural Science Foundation of China,No.82202718the Natural Science Foundation of Beijing,No.L212050the China Postdoctoral Science Foundation,Nos.2019M664007,2021T140793(all to ZL)。
文摘Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.
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 grants from the National Natural Science Foundation of China(82172106,32050410286)and Tian-jin"Project+Team"Key Training Foundation(XC202035)Science and Technology Commission of Shanghai Municipality(19441902600,20S31900900,20DZ2254900)。
文摘Cardiovascular diseases cause huge morbidity and mortality worldwide.Recently,vascular stents have been most frequently used to treat cardiovascular diseases thanks to their effectiveness at dilating blood vessels and main-taining the circulation of blood.However,stent expansion leads to endothelium injury posing thrombogenic and in-stent restenosis(ISR).In addition,the bioinertness and an acute lack of endothelium-like function on the surface of implanted vascular stents compromise their performance.Functional coatings of vascular stents to mimic endothelium-and extracellular matrix(ECM)-like functions could prevent thrombosis,inhibit the over-growth of smooth muscle cells(SMCs),and promote the rapid restoration of native endothelium,hence effec-tively suppressing stent-related complications.Noticeably,ECM-based coatings including a multitude of bioactive molecular,such as growth factors,heparin,hyaluronic acid(HA)and so on,have been proven to play important effects on regulating ECs/SMCs behavior and improving blood compatibility of stents.Additionally,nitric oxide(NO),which is fundamental to the endothelium-mediated anti-thrombogenesity,anti-intimal hyperplasia and anti-inflammation,has been leveraged to improve vascular stent functions.Therefore,this review will highlight different strategies and biological role of ECM and NO based functional coatings on vascular stent.Lastly,some potential important factors for stents development are suggested as well.