Nitric oxide(NO)and hydrogen sulfide(H_(2)S)gasotransmitters exhibit potential therapeutic effects in the car-diovascular system.Herein,biomimicking multilayer structures of biological blood vessels,bilayer smalldiame...Nitric oxide(NO)and hydrogen sulfide(H_(2)S)gasotransmitters exhibit potential therapeutic effects in the car-diovascular system.Herein,biomimicking multilayer structures of biological blood vessels,bilayer smalldiameter vascular grafts(SDVGs)with on-demand NO and H_(2)S release capabilities,were designed and fabri-cated.The keratin-based H_(2)S donor(KTC)with good biocompatibility and high stability was first synthesized and then electrospun with poly(L-lactide-co-caprolactone)(PLCL)to be used as the outer layer of grafts.The elec-trospun poly(ε-caprolactone)(PCL)mats were aminolyzed and further chelated with copper(II)ions to construct glutathione peroxidase(GPx)-like structural surfaces for the catalytic generation of NO,which acted as the inner layer of grafts.The on-demand release of NO and H_(2)S selectively and synergistically promoted the proliferation and migration of human umbilical vein endothelial cells(HUVECs)while inhibiting the proliferation and migration of human umbilical artery smooth muscle cells(HUASMCs).Dual releases of NO and H_(2)S gaso-transmitters could enhance their respective production,resulting in enhanced promotion of HUVECs and inhi-bition of HUASMCs owing to their combined actions.In addition,the bilayer grafts were conducive to forming endothelial cell layers under flow shear stress.In rat abdominal aorta replacement models,the grafts remained patency for 6 months.These grafts were capable of facilitating rapid endothelialization and alleviating neo-intimal hyperplasia without obvious injury,inflammation,or thrombosis.More importantly,the grafts were expected to avoid calcification with the degradation of the grafts.Taken together,these bilayer grafts will be greatly promising candidates for SDVGs with rapid endothelialization and anti-calcification properties.展开更多
The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the t...The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the two figures are as below.The authors apologize for any inconvenience caused and state that this does not change the discussion and the scientific conclusions of the article.展开更多
The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the t...The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the two figures are as below.The authors apologize for any inconvenience caused and state that this does not change the discussion and the scientific conclusions of the article.展开更多
Good’s buffers have been widely applied in cell/organ culture over the past half a century as biocompatible pH stabilizers.However,the emergence of severe adverse effects,such as cellular uptake,lysosomal autophagic ...Good’s buffers have been widely applied in cell/organ culture over the past half a century as biocompatible pH stabilizers.However,the emergence of severe adverse effects,such as cellular uptake,lysosomal autophagic activation,and visible light-induced cytotoxicity,raises serious questions over its biocompatibility while underlying mechanism was unclear.Here we report that riboflavin(RF,component of cell culture medium)generates ^(1)O_(2),⋅OH,and O_(2)^(·-)under visible light exposure during regular cell manipulation.These short half-life reactive oxygen species(ROS)react with tertiary amine groups of HEPES,producing 106.6μM of H_(2)O_(2).Orders of magnitude elevated half-life of ROS in the medium caused severe cytotoxicity and systematic disorder of normal cell functions.We have further designed and validated zwitterionic betaines as the new generation biocompatible organic pH buffers,which is able to completely avoid the adverse effects that found on HEPES and derivate Good’s buffers.These findings may also open a new avenue for zwitterionic betaine based materials for biomedical applications.展开更多
Developing advanced technologies to address the bacterial associated infections is an urgent requirement for metallic implants and devices.Here,we report a novel phosphonate/quaternary amine block polymer as the high-...Developing advanced technologies to address the bacterial associated infections is an urgent requirement for metallic implants and devices.Here,we report a novel phosphonate/quaternary amine block polymer as the high-efficiency antibacterial coating for metallic substrates.Three pDEMMP-b-pTMAEMA block polymers that bearing identical phosphonate segments(repeat units of 15)but varied cationic segments(repeat units of 8,45,and 70)were precisely prepared.Stable cationic polymer coatings were constructed on TC4 substrates based on the strong covalent binding between phosphonate group and metallic substrate.Robust relationship between the segment chain length of the polymer coating and the antibacterial property endowed to the substrates have been established based on quantitative and qualitative evaluations.Results showed that the antibacterial rate of the modified TC4 surface were 95.8%of S.aureus and 92.9%of E.coli cells attached.Interestingly,unlike the cationic free polymer or cationic hydrogels,the surface anchored cationic polymers do compromise the viability of the attached C2C12 cells but without significant cytotoxicity.In addition,the phosphonate/quate rnary amine block polymers can be easily constructed on titanium,stainless steel,and Ni/Cr alloy with significantly improved antibacterial property,indicating the generality of the block polymer for surface antibacterial modification of bio-metals.展开更多
Nitric oxide(NO)plays an important role in wound healing,due to its ability to contract wound surfaces,dilate blood vessels,participate in inflammation as well as promote collagen synthesis,angiogenesis and fibroblast...Nitric oxide(NO)plays an important role in wound healing,due to its ability to contract wound surfaces,dilate blood vessels,participate in inflammation as well as promote collagen synthesis,angiogenesis and fibroblast proliferation.Herein,keratin was first nitrosated to afford S-nitrosated keratin(KSNO).As a NO donor,KSNO was then co-electrospun with polyurethane(PU).These as-spun PU/KSNO biocomposite mats could release NO sustainably for 72 h,matching the renewal time of the wound dressing.Moreover,these mats exhibited excellent cytocompatibility with good cell adhesion and cell migration.Further,the biocomposite mats exhibited antibacterial properties without inducing severe inflammatory responses.The wound repair in vivo demonstrated that these mats accelerated wound healing by promoting tissue formation,collagen deposition,cell migration,re-epithelialization and angiogenesis.Overall,PU/KSNO mats may be promising candidates for wound dressing.展开更多
Antifouling ability and blood compatibility are critically important in the development of medical metallic implants for clinical applications.Here,we report the zwitterionic-phosphonate block polymer as a new type of...Antifouling ability and blood compatibility are critically important in the development of medical metallic implants for clinical applications.Here,we report the zwitterionic-phosphonate block polymer as a new type of high-efficiency antifouling coating for metallic substrates.Six block polymers(pSBMA-b-pDEMMP)with different segment lengths(nSBMA:nDEMMP=10:25,40:25,100:25,75:5,75:40,75:100)were prepared and anchored on titanium alloy(TC4)substrates.1H nuclear magnetic resonance(NMR)results clearly showed the precise preparation of the block polymers.XPS analysis and water contact angle measurement indicated the successful construction of the block polymer on TC4 substrates.The relationship between the antifouling performance of the polymer coating and the length of pDEMMP and pSBMA segments in the block polymer was established.Results showed that the polymer containing the pSBMA segment above 40 repeat units could significantly inhibit protein adsorption,platelet adhesion,bacterial adhesion and cell adhesion,while the pDEMMP segment above 5 repeat units is able to generate stable zwitterionic polymer coating on TC4 substrates.This ease of production and high-efficiency antifouling modification strategy elucidated here may find broad application for biomedical implants and devices in clinical applications.展开更多
Composite biomaterials made of biodegradable polylactic acid （PLA） and bioactive magnesium （Mg） salt are developed for orthopaedic implants or metal implant coatings. The releasing of Mg salt into the biological e...Composite biomaterials made of biodegradable polylactic acid （PLA） and bioactive magnesium （Mg） salt are developed for orthopaedic implants or metal implant coatings. The releasing of Mg salt into the biological environment benefits the bone growth, while with the releasing of Mg salt and degradation of PLA there forms a porous scaffold for tissue engineering. The size and morphology of the salt and voids are adjustable with such preparation conditions as salt content, pH of casting solution, and the solidification rate, so that we can control the salt releasing and degradation rate of PLA. Dielectric spectroscopy is used to investigate the dispersive structures of Mg salt and voids in the polymer matrix and to monitor the in situ releasing of Mg salts in the simulated body fluid （SBF）. The current study provides us with an orthopedic biomaterial with controllable multi-phase structures, and a tool to investigate the in vivo behaviors of biomaterials.展开更多
基金supported by the National Natural Science Fund of China(81873923)Jiangsu Higher Education Institutions(19KJA310001 and PAPD)Jiangsu Collaborative Innovation Center of Biomedical Functional Materials.
文摘Nitric oxide(NO)and hydrogen sulfide(H_(2)S)gasotransmitters exhibit potential therapeutic effects in the car-diovascular system.Herein,biomimicking multilayer structures of biological blood vessels,bilayer smalldiameter vascular grafts(SDVGs)with on-demand NO and H_(2)S release capabilities,were designed and fabri-cated.The keratin-based H_(2)S donor(KTC)with good biocompatibility and high stability was first synthesized and then electrospun with poly(L-lactide-co-caprolactone)(PLCL)to be used as the outer layer of grafts.The elec-trospun poly(ε-caprolactone)(PCL)mats were aminolyzed and further chelated with copper(II)ions to construct glutathione peroxidase(GPx)-like structural surfaces for the catalytic generation of NO,which acted as the inner layer of grafts.The on-demand release of NO and H_(2)S selectively and synergistically promoted the proliferation and migration of human umbilical vein endothelial cells(HUVECs)while inhibiting the proliferation and migration of human umbilical artery smooth muscle cells(HUASMCs).Dual releases of NO and H_(2)S gaso-transmitters could enhance their respective production,resulting in enhanced promotion of HUVECs and inhi-bition of HUASMCs owing to their combined actions.In addition,the bilayer grafts were conducive to forming endothelial cell layers under flow shear stress.In rat abdominal aorta replacement models,the grafts remained patency for 6 months.These grafts were capable of facilitating rapid endothelialization and alleviating neo-intimal hyperplasia without obvious injury,inflammation,or thrombosis.More importantly,the grafts were expected to avoid calcification with the degradation of the grafts.Taken together,these bilayer grafts will be greatly promising candidates for SDVGs with rapid endothelialization and anti-calcification properties.
文摘The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the two figures are as below.The authors apologize for any inconvenience caused and state that this does not change the discussion and the scientific conclusions of the article.
文摘The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the two figures are as below.The authors apologize for any inconvenience caused and state that this does not change the discussion and the scientific conclusions of the article.
基金support from National Natural Science Foundation of China(No.21504046)Natural Science Foundation of Jiangsu Province(No.BK20150970)+1 种基金the Six Talent Peaks Project in Jiangsu Province(SWYY-060)the Projects of Nanjing Normal University(No.184080H20192,184080H10386).
文摘Good’s buffers have been widely applied in cell/organ culture over the past half a century as biocompatible pH stabilizers.However,the emergence of severe adverse effects,such as cellular uptake,lysosomal autophagic activation,and visible light-induced cytotoxicity,raises serious questions over its biocompatibility while underlying mechanism was unclear.Here we report that riboflavin(RF,component of cell culture medium)generates ^(1)O_(2),⋅OH,and O_(2)^(·-)under visible light exposure during regular cell manipulation.These short half-life reactive oxygen species(ROS)react with tertiary amine groups of HEPES,producing 106.6μM of H_(2)O_(2).Orders of magnitude elevated half-life of ROS in the medium caused severe cytotoxicity and systematic disorder of normal cell functions.We have further designed and validated zwitterionic betaines as the new generation biocompatible organic pH buffers,which is able to completely avoid the adverse effects that found on HEPES and derivate Good’s buffers.These findings may also open a new avenue for zwitterionic betaine based materials for biomedical applications.
基金the grant supports from the National Natural Science Foundation of China(No.21504046)the Six Talent Peaks Project in Jiangsu Province(SWYY-060)+1 种基金the Projects of Nanjing Normal University(No.184080H20192184080H10386)。
文摘Developing advanced technologies to address the bacterial associated infections is an urgent requirement for metallic implants and devices.Here,we report a novel phosphonate/quaternary amine block polymer as the high-efficiency antibacterial coating for metallic substrates.Three pDEMMP-b-pTMAEMA block polymers that bearing identical phosphonate segments(repeat units of 15)but varied cationic segments(repeat units of 8,45,and 70)were precisely prepared.Stable cationic polymer coatings were constructed on TC4 substrates based on the strong covalent binding between phosphonate group and metallic substrate.Robust relationship between the segment chain length of the polymer coating and the antibacterial property endowed to the substrates have been established based on quantitative and qualitative evaluations.Results showed that the antibacterial rate of the modified TC4 surface were 95.8%of S.aureus and 92.9%of E.coli cells attached.Interestingly,unlike the cationic free polymer or cationic hydrogels,the surface anchored cationic polymers do compromise the viability of the attached C2C12 cells but without significant cytotoxicity.In addition,the phosphonate/quate rnary amine block polymers can be easily constructed on titanium,stainless steel,and Ni/Cr alloy with significantly improved antibacterial property,indicating the generality of the block polymer for surface antibacterial modification of bio-metals.
基金support from Jiangsu Higher Education Institutions(19KJA310001,PAPD).
文摘Nitric oxide(NO)plays an important role in wound healing,due to its ability to contract wound surfaces,dilate blood vessels,participate in inflammation as well as promote collagen synthesis,angiogenesis and fibroblast proliferation.Herein,keratin was first nitrosated to afford S-nitrosated keratin(KSNO).As a NO donor,KSNO was then co-electrospun with polyurethane(PU).These as-spun PU/KSNO biocomposite mats could release NO sustainably for 72 h,matching the renewal time of the wound dressing.Moreover,these mats exhibited excellent cytocompatibility with good cell adhesion and cell migration.Further,the biocomposite mats exhibited antibacterial properties without inducing severe inflammatory responses.The wound repair in vivo demonstrated that these mats accelerated wound healing by promoting tissue formation,collagen deposition,cell migration,re-epithelialization and angiogenesis.Overall,PU/KSNO mats may be promising candidates for wound dressing.
基金This work was financially supported by the Six Talent Peaks Project in Jiangsu Province(No.SWYY-060)the National Natural Science Foundation of China(No.21504046)the Projects of Nanjing Normal University(Nos.184080H20192,184080H10386 and 184080H202B283).
文摘Antifouling ability and blood compatibility are critically important in the development of medical metallic implants for clinical applications.Here,we report the zwitterionic-phosphonate block polymer as a new type of high-efficiency antifouling coating for metallic substrates.Six block polymers(pSBMA-b-pDEMMP)with different segment lengths(nSBMA:nDEMMP=10:25,40:25,100:25,75:5,75:40,75:100)were prepared and anchored on titanium alloy(TC4)substrates.1H nuclear magnetic resonance(NMR)results clearly showed the precise preparation of the block polymers.XPS analysis and water contact angle measurement indicated the successful construction of the block polymer on TC4 substrates.The relationship between the antifouling performance of the polymer coating and the length of pDEMMP and pSBMA segments in the block polymer was established.Results showed that the polymer containing the pSBMA segment above 40 repeat units could significantly inhibit protein adsorption,platelet adhesion,bacterial adhesion and cell adhesion,while the pDEMMP segment above 5 repeat units is able to generate stable zwitterionic polymer coating on TC4 substrates.This ease of production and high-efficiency antifouling modification strategy elucidated here may find broad application for biomedical implants and devices in clinical applications.
基金financially supported by the National Natural Scientific Foundation of China(Nos.50773077,20934005 and 51273091)the Hong Kong Special Administration Region Earmarked Projects(CUHK4042/09P,2160396)
文摘Composite biomaterials made of biodegradable polylactic acid （PLA） and bioactive magnesium （Mg） salt are developed for orthopaedic implants or metal implant coatings. The releasing of Mg salt into the biological environment benefits the bone growth, while with the releasing of Mg salt and degradation of PLA there forms a porous scaffold for tissue engineering. The size and morphology of the salt and voids are adjustable with such preparation conditions as salt content, pH of casting solution, and the solidification rate, so that we can control the salt releasing and degradation rate of PLA. Dielectric spectroscopy is used to investigate the dispersive structures of Mg salt and voids in the polymer matrix and to monitor the in situ releasing of Mg salts in the simulated body fluid （SBF）. The current study provides us with an orthopedic biomaterial with controllable multi-phase structures, and a tool to investigate the in vivo behaviors of biomaterials.
