The monomer of phosphorylcholine derivative, O-(5-（2-methacryloxy）-3, 3-dimethyl-3-azapentyl)-O’-（ω-hydroxy-octyl）-phosphatequaternary ammonium salt, was designed and synthesized successfully. It was characteriz...The monomer of phosphorylcholine derivative, O-(5-（2-methacryloxy）-3, 3-dimethyl-3-azapentyl)-O’-（ω-hydroxy-octyl）-phosphatequaternary ammonium salt, was designed and synthesized successfully. It was characterized by the spectra ofHNMR and Mass spectra （ESI+）, and every signal was assigned. Then the lubricating characteristics of the phosphorylcholinederivative were investigated on the tribological setup of ball-oh-flat. The Ultra-High Molecular Weight Polyethylene（UHMWPE） flat was rotated against a stainless steel ball with 6 mm diameter. The load was 2.3 N, which corresponded to amaximal Hertz contact pressure of 29 MPa. Water, phosphorylcholine derivative, and Acrylic Acid （AA） solution were used aslubricants, respectively. Compared with AA, the phosphorylcholine derivative shows significant lubrication. It can be stronglyhydrated under water due to the charged segment in chemical structure. The thick water layers within the chains serves asboundary lubricants, and this is thought to be the molecular origins of lubricating behavior.展开更多
Modification of poly(tetrafluoroethylene)(PTFE) films with 2-methacryloyloxyethyl phosphorylcholine(MPC) was performed by low-temperature plasma treatment and grafting polymerization.Surface properties of PTFE were ch...Modification of poly(tetrafluoroethylene)(PTFE) films with 2-methacryloyloxyethyl phosphorylcholine(MPC) was performed by low-temperature plasma treatment and grafting polymerization.Surface properties of PTFE were characterized by attenuated total reflectance Fourier transform infrared(ATR-FTIR) spectra,X-ray photoelectron spectroscopy(XPS) ,and static contact angle.The results show that MPC has been grafted onto PTFE film surface successfully.Contact angle for the modified PTFE films in the water decreased from 108°to 58.25°,while surface energy increased from 17.52 mN/m to 45.47 mN/m.The effects of plasma treatment time,monomer concentration and grafting time on degree of grafting were determined.In the meanwhile,blood compatibility of the PTFE films was studied by checking thrombogenic time of blood plasma.展开更多
A new phosphorylcholine, (6-hydroxy) hexyl-2-(trimethylammonio) ethyl phosphate (HTEP), was synthesized andcharasterized. Segmented polyurethane (SPU) containing phosphorylcholine structure was synthesized based ondip...A new phosphorylcholine, (6-hydroxy) hexyl-2-(trimethylammonio) ethyl phosphate (HTEP), was synthesized andcharasterized. Segmented polyurethane (SPU) containing phosphorylcholine structure was synthesized based ondiphenylmethane diisocyanate (MDI), soft segment polytetramethylene glycol (PTMG) and HTEP, with 1,4-butanediol (BD)as a chain extender. The existence of phosphorylcholine structure on the surface of SPU was revealed by attenuated totalreflectance Fourier transform infrard spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and water contactangle measurements. The blood compatibilities of the polymers were evaluated by hemolytic testing and a platelet-richplasma (PRP) adhesion experiment, which was viewed by scanning electron microscopy (SEM) with polyurethane as areference. The novel segmented polyurethane containing phosphorylcholine structure showed improved blood compatibility.展开更多
The water-soluble Ag nanoparticles capped with novel zwitterionic thioalkylated phosphorylcholine were synthesized.The Ag nanoparticles showed remarkable stability in saline media with salt concen-trations as high as ...The water-soluble Ag nanoparticles capped with novel zwitterionic thioalkylated phosphorylcholine were synthesized.The Ag nanoparticles showed remarkable stability in saline media with salt concen-trations as high as 2.0 mol/L and plasma using UV-vis absorption spectroscopy.Similarly,compared with tiopronin and citrate-protected Ag nanoparticles,the zwitterionic phosphorylcholine Ag nanopar-ticles did not precipitate out of solution when charged polyelectrolytes or biopolymers were added.The zwitterionic phosphorylcholine might be a better ligand for stabilizing metal nanoparticles.展开更多
In this work, the biocompatibility of a biomimetic, fully biodegradable ionomer phosphorylcholine (PC)-functionalized poly(butylene succinate) (PBS-PC) was investigated by means of hemolysis, platelet adhesion, protei...In this work, the biocompatibility of a biomimetic, fully biodegradable ionomer phosphorylcholine (PC)-functionalized poly(butylene succinate) (PBS-PC) was investigated by means of hemolysis, platelet adhesion, protein adsorption and cytotox- icity experiments. The reference materials were poly(butylene succinate) (PBS) and chloroethylphosphoryl functionalized poly(butylene succinate) (PBS-Cl). The hemolysis rates (HR) of the leaching solutions of PBS, PBS-Cl and PBS-PC were all lower than the safe value, and the rate of PBS-PC was reduced to 1.07%. Scanning electron microscopy (SEM) measurements showed that platelet adhesion and aggregation were significant on both PBS and PBS-Cl surface. In contrast, very few platelets were observed on PBS-PC surface. Bicinchoninic acid (BCA) measurements revealed that the adsorption amounts of bovine serum albumin (BSA) and bovine plasma fibrinogen (BPF) on PBS-PC surface were 52% and 72% reduction respectively compared with those on PBS surface. Moreover, non-cytotoxicity of both PBS-PC particles and its leaching solution was sug- gested by MTT assay using mouse L929 fibroblast cells. All the results demonstrated that the biocompatibility of PBS could be greatly improved by PC end-capping strategy. This PC functionalized polyester may have potential applications in biological environments as a novel carrier for controlled drug release and scaffold for tissue engineering.展开更多
Zwitterionic materials are now widely used to fabricate various functionalized surfaces for biomedical applications due to their excellent non-fouling properties.However,a newly-discovered zwitterionic material,cholin...Zwitterionic materials are now widely used to fabricate various functionalized surfaces for biomedical applications due to their excellent non-fouling properties.However,a newly-discovered zwitterionic material,choline phosphate(CP),was reported to be cell-adhesive,which makes it different from traditional non-fouling zwitterionic materials such as sulfobetaine,carboxybetaine and phosphorylcholine(PC).To further investigate the properties of CP,a comparative study was conducted and the widely-reported zwitterionic PC was employed as a control which has the same chemical component but opposite orientation of charged groups with CP.For this purpose,CP and PC-functionalized surfaces were prepared by surface-initiated atom transfer radical polymerization(Si-ATRP),and their non-fouling properties were probed by protein adsorption and eukaryotic cell adhesion measurement.Results showed that CP-functionalized surfaces exhibited almost equivalent amounts of adsorbed proteins to that of PC,but they were more beneficial to cells initial adhesion and further spreading in serum-free medium,indicating that CP had a promising prospect of application in tissue engineering.展开更多
Inspired by nature,hydrophilic diblock brush copolymers containing both phosphorylcholine groups and poly(ethylene oxide)(PEO)side chains were synthesized by successive reversible addition-fragmentation chain transfer...Inspired by nature,hydrophilic diblock brush copolymers containing both phosphorylcholine groups and poly(ethylene oxide)(PEO)side chains were synthesized by successive reversible addition-fragmentation chain transfer(RAFT)polymerization of the zwitterionic monomer 2-methacryloyloxyethyl phosphorylcholine(MPC)and the PEO-containing macromonomer poly(ethylene oxide)methyl ether methacrylate(PEOMEMA)for the first time.The lubricating effect of several diblock brush copolymers and one gradient copolymer of MPC and PEOMEMA was evaluated by tribological measurements in polydimethylsiloxane(PDMS)-glass and cartilage-glass systems which were placed in phosphate-buffered saline(PBS)solutions of the polymers.The best lubrication was provided by the diblock copolymer with a relatively long poly(2-methacryloyloxyethyl phosphorylcholine)(pMPC)block and the copolymer of gradient structure.The average dynamic coefficient of friction(COF)in the PDMS-glass system at a copolymer concentration of0.4 mg/mL was only 0.004-0.007,while COF values of the copolymers in the cartilage-glass system after 450 sliding cycles reached 0.06-0.07.The excellent lubrication effect of the diblock and gradient copolymers of MPC and PEOMEMA is attributed to hydration lubrication provided by pMPC synergistically combined with steric repulsion from PEOMEMA.Entrapment of diblock brush copolymers between sliding surfaces was sufficient to provide effective lubrication,thus enhancing the efficacy of the diblock brush copolymers as potential additives for intraarticular injections.展开更多
A series of fluorinated phosphatidylcholine polyurethane macromolecular additives were synthesized by solution polymerization using methylenebis（phylene isocyanates） （MDI） and 1,4-butanediol （BDO） as hard segmen...A series of fluorinated phosphatidylcholine polyurethane macromolecular additives were synthesized by solution polymerization using methylenebis（phylene isocyanates） （MDI） and 1,4-butanediol （BDO） as hard segments, a new phoshporycholine, 2-（2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-hexadecafluoro-10-（2-hydroxyethoxy）decyloxy） ethyl phosphorycholine （HDFOPC） as end-capper, and four polydiols, poly（tetramethylene glycol）s （PTMG）, polydimethylsiloxane （PDMS）, poly（1,6-hexyl-1,5-pentylcarbonate） （PHPC） and poly（propylene glycol） （PPG） as soft segments, respectively. The chemical structures of the synthesized polyurethanes were characterized by 1H-NMR and FTIR. DSC and DMA were employed to study the phase behavior of these novel polyurethanes due to their great influences on the surface properties, and hence their interactions with bio-systems. The results showed that phase separation of the fluorinated phosphatidylcholine end-capped polyurethanes was increased in comparison with that of normal polyurethanes. The effect of fluorinated phosphatidylcholine end-capped groups on the phase behavior was further demonstrated by analyzing the degree of hydrogen-bonding between hard and soft segments.展开更多
The surface design used for improving biocompatibility is one of the most important issues for the fabrication of medical devices. For mimicking the ideal surface structure of cell outer membrane, a large number of po...The surface design used for improving biocompatibility is one of the most important issues for the fabrication of medical devices. For mimicking the ideal surface structure of cell outer membrane, a large number of polymers bearing phosphorylcholine （PC） groups have been employed to modify the surfaces of biomaterials and medical devices. It has been demonstrated that the biocompatibility of the modified materials whose surface is required to interact with a living organism has been obviously improved by introducing PC groups. In this review, the fabrication strategies of cell outer membrane mimetic surfaces and their resulted biocompatibilities were summarized.展开更多
Some Pseudomonas syringae pathovars secrete tabtoxin, a monocyclic β-lactam antibiotic, responsible for chlorosis, the principal halo blight symptom in susceptible plants as oats, rye, barley, wheat and sorghum, amon...Some Pseudomonas syringae pathovars secrete tabtoxin, a monocyclic β-lactam antibiotic, responsible for chlorosis, the principal halo blight symptom in susceptible plants as oats, rye, barley, wheat and sorghum, among other. Here, we demonstrated that the production of tabtoxin in a P. syringae strain increased at least 150%, when choline, betaine or dimethylglycine were used as nitrogen source, or when choline was added as osmoprotectant in hyperosmolar culture media. Besides, we investigated the induction of phosphorylcholine phosphatase (PchP) activity when choline or its metabolites were used as nitrogen sources. PchP is an enzyme involved in Pseudomonas aeruginosa pathogenesis through its contribution to the breakdown of choline-containing compounds of the host cells. Considering these results and that the success of a pathogenic microorganism depends on its ability to survive and proliferate in its target tissue, we propose that choline is one of the plant signals that contribute to establishment of the infection by tabtoxin-producing strains of P. syringae.展开更多
Background Although flow diverter device(FDD)has brought revolutionized advances in endovascular treatment of intracranial aneurysms,it also presents considerable drawbacks as well,as the innovation for novel device h...Background Although flow diverter device(FDD)has brought revolutionized advances in endovascular treatment of intracranial aneurysms,it also presents considerable drawbacks as well,as the innovation for novel device has never stopped.This preclinical research aims to evaluate the safety and efficacy of a newly developed FDD,the EMBOPIPE,through in vivo and in vitro experiments.Methods Aneurysms were induced in 20 New Zealand white rabbits which were randomized to three follow-up groups according to the time elapsed after EMBOPIPE implantation(28,90,and 180 days).Additional EMBOPIPEs were implanted in the abdominal aorta to cover the renal artery in nine rabbits.Angiography was performed immediately after device placement in all groups.Aneurysm occlusion,patency of renal arteries,and pathological outcomes were assessed.For the in vitro experiments,we measured the thrombogenic potential of EMBOPIPEs(n=5)compared with bare stents(n=5)using the Chandler loop model.Evaluation indicators were the platelet counts,macroscopic observations and scanning electron microscopy.Results EMBOPIPEs were successfully deployed in 19 of 20 rabbit aneurysms(95.0%).The rates of complete or near-complete aneurysm occlusion were 73.3%,83.3%,and 100%in the 28-,90-,and 180-day groups,respectively.All renal arteries covered by EMBOPIPEs remained patent,and the mean difference in renal artery diameter before and after the device placement in the three groups was 0.07 mm,0.10 mm,and 0.10 mm,respectively(p=0.77).Renal pathology was normal in all cases.The pathological findings of the aneurysms were as follows:thickened and adequate neointimal coverage at the aneurysm neck,minimal inflammatory response,near-complete smooth muscle cell layer,and endothelialization along the device.In vitro experiments showed that the platelet counts were significantly higher in EMBOPIPE blood samples than in bare stent samples and that platelet adhesion to the device was lower in the EMBOPIPE stent struts compared with bare stent struts through macroscopic observations and scanning electron microscopy.Conclusions The EMBOPIPE can achieve high rates of aneurysm occlusion while maintaining excellent branch artery patency.It exhibited wonderful pathological results.This novel device with phosphorylcholine surface modification could reduce platelet thrombus attached to the stent struts.展开更多
Modification of biomaterials surface by mimetic cell membrane for improving biocompatibility, to imitate the excellent biological and physiological proper- ties of the natural cell membrane, is an important research a...Modification of biomaterials surface by mimetic cell membrane for improving biocompatibility, to imitate the excellent biological and physiological proper- ties of the natural cell membrane, is an important research area in materials science. Numerous studies have been attempted to construct a mimetic cell membrane biointer- face composed of phosphorylcholine （PC）-containing polymers or other phospholipid analogues on biomaterials surface. PC-containing biointerfaces show outstanding characteristics, especially in biological aspects such as blood compatibility and antifouling property. In this mini-review, the strategies of membrane mimetic modification of biomaterials and their antifouling applications are summarized.展开更多
Thrombus formation and blood coagulation are serious problems associated with blood contacting products,such as catheters,vascular grafts,artificial hearts,and heart valves.Recent progresses and strategies to improve ...Thrombus formation and blood coagulation are serious problems associated with blood contacting products,such as catheters,vascular grafts,artificial hearts,and heart valves.Recent progresses and strategies to improve the hemocompatibility of biomaterials by surface modification using photochemical immobilization and photograft polymerization are reviewed in this paper.Three approaches to modify biomaterial surfaces for improving the hemocompatibility,i.e.,bioinert surfaces,immobilization of anticoagulative substances and biomimetic surfaces,are introduced.The biomimetic amphiphilic phosphorylcholine and Arg-Gly-Asp(RGD)sequence are the most effective and most often employed biomolecules and peptide sequence for improving hemocompatibility of material surfaces.The RGD sequence can enhance adhesion and growth of endothelial cells(ECs)on material surfaces and increase the retention of ECs under flow shear stress conditions.This surface modification is a promising strategy for biomaterials especially for cardiovascular grafts and functional tissue engineered blood vessels.展开更多
Osteoarthritis is associated with the significantly increased friction of the joint,which results in progressive and irreversible damage to the articular cartilage.A synergistic therapy integrating lubrication enhance...Osteoarthritis is associated with the significantly increased friction of the joint,which results in progressive and irreversible damage to the articular cartilage.A synergistic therapy integrating lubrication enhancement and drug delivery is recently proposed for the treatment of early-stage osteoarthritis.In the present study,bioinspired by the self-adhesion performance of mussels and super-lubrication property of articular cartilages,a biomimetic self-adhesive dopamine methacrylamide-poly(2-methacryloyloxyethyl phosphorylcholine)(DMA-MPC)copolymer was designed and synthesized via free radical polymerization.The copolymer was successfully modified onto the surface of biodegradable mesoporous silica nanoparticles(bMSNs)by the dip-coating method to prepare the dual-functional nanoparticles(bMSNs@DMA-MPC),which were evaluated using a series of surface characterizations including the transmission electron microscope(TEM),Fourier transform infrared(FTIR)spectrum,thermogravimetric analysis(TGA),X-ray photoelectron spectroscopy(XPS),etc.The tribological test and in vitro drug release test demonstrated that the developed nanoparticles were endowed with improved lubrication performance and achieved the sustained release of an anti-inflammatory drug,i.e.,diclofenac sodium(DS).In addition,the in vitro biodegradation test showed that the nanoparticles were almost completely biodegraded within 10 d.Furthermore,the dual-functional nanoparticles were biocompatible and effectively reduced the expression levels of two inflammation factors such as interleukin-1β(IL-1β)and interleukin-6(IL-6).In summary,the surface functionalized nanoparticles with improved lubrication and local drug release can be applied as a potential intra-articularly injected biolubricant for synergistic treatment of early-stage osteoarthritis.展开更多
The synergistic effect of polyethylene glycol(PEG)and poly(2-methacry-loyloxyethyl phosphorytcholine)(PMPC)can effectively reduce the protein absorption,which is beneficial to theranostics.However,PEG-PMPC-based polym...The synergistic effect of polyethylene glycol(PEG)and poly(2-methacry-loyloxyethyl phosphorytcholine)(PMPC)can effectively reduce the protein absorption,which is beneficial to theranostics.However,PEG-PMPC-based polymers have rarely been used as nanocarriers in the theranostic field due to their limited modifiability and weak interaction with other materials.Herein,a plain method was proposed to endow them with the probable ability of loading small active agents,and the relationship between the structure and the ability of loading hydrophobic agents was explored,thus expanding their applications.Firstly,mPEG-PMPC or 4-arm-PEG-PMPC polymer was synthesized by atom transfer radical polymerization(ATRP)using mPEG-Br or 4-arm-PEG-Br as the macroinitiator.Then a strong hydrophobic segment,poly(butyl methacrylate)(PBMA),was introduced and the ability to load small hydrophobic agents was further explored.The results showed that linear mPEG-PMPC-PBMA could form micelles 50-80 nm in size and load the hydrophobic agent such as Nile red efficiently.In contrast,star-like 4-arm-PEG-PMPC-PBiyiA,a monomolecular micelle(10-20 nm),could hardly load any hydrophobic agent.This work highlights effective strategies for engineering PEG-PMPC-based polymers and may facilitate the further application in numerous fields.展开更多
基金the National Natural Science Foundation of China(50975145)the High Technology Project of Jiangsu Province(BC20077046)for their financial support
文摘The monomer of phosphorylcholine derivative, O-(5-（2-methacryloxy）-3, 3-dimethyl-3-azapentyl)-O’-（ω-hydroxy-octyl）-phosphatequaternary ammonium salt, was designed and synthesized successfully. It was characterized by the spectra ofHNMR and Mass spectra （ESI+）, and every signal was assigned. Then the lubricating characteristics of the phosphorylcholinederivative were investigated on the tribological setup of ball-oh-flat. The Ultra-High Molecular Weight Polyethylene（UHMWPE） flat was rotated against a stainless steel ball with 6 mm diameter. The load was 2.3 N, which corresponded to amaximal Hertz contact pressure of 29 MPa. Water, phosphorylcholine derivative, and Acrylic Acid （AA） solution were used aslubricants, respectively. Compared with AA, the phosphorylcholine derivative shows significant lubrication. It can be stronglyhydrated under water due to the charged segment in chemical structure. The thick water layers within the chains serves asboundary lubricants, and this is thought to be the molecular origins of lubricating behavior.
文摘Modification of poly(tetrafluoroethylene)(PTFE) films with 2-methacryloyloxyethyl phosphorylcholine(MPC) was performed by low-temperature plasma treatment and grafting polymerization.Surface properties of PTFE were characterized by attenuated total reflectance Fourier transform infrared(ATR-FTIR) spectra,X-ray photoelectron spectroscopy(XPS) ,and static contact angle.The results show that MPC has been grafted onto PTFE film surface successfully.Contact angle for the modified PTFE films in the water decreased from 108°to 58.25°,while surface energy increased from 17.52 mN/m to 45.47 mN/m.The effects of plasma treatment time,monomer concentration and grafting time on degree of grafting were determined.In the meanwhile,blood compatibility of the PTFE films was studied by checking thrombogenic time of blood plasma.
基金Supported by the Special Funds for Major State Basic Research Projects (G1999064705)
文摘A new phosphorylcholine, (6-hydroxy) hexyl-2-(trimethylammonio) ethyl phosphate (HTEP), was synthesized andcharasterized. Segmented polyurethane (SPU) containing phosphorylcholine structure was synthesized based ondiphenylmethane diisocyanate (MDI), soft segment polytetramethylene glycol (PTMG) and HTEP, with 1,4-butanediol (BD)as a chain extender. The existence of phosphorylcholine structure on the surface of SPU was revealed by attenuated totalreflectance Fourier transform infrard spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and water contactangle measurements. The blood compatibilities of the polymers were evaluated by hemolytic testing and a platelet-richplasma (PRP) adhesion experiment, which was viewed by scanning electron microscopy (SEM) with polyurethane as areference. The novel segmented polyurethane containing phosphorylcholine structure showed improved blood compatibility.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 20774082 and 50703036)National High Technology Research and Development Program of China (Grant Nos. 2006AA03Z329 and 2006AA032444)Science and Technology Projects of Zhejiang Province (Grant No. 2007C24G2010020)
文摘The water-soluble Ag nanoparticles capped with novel zwitterionic thioalkylated phosphorylcholine were synthesized.The Ag nanoparticles showed remarkable stability in saline media with salt concen-trations as high as 2.0 mol/L and plasma using UV-vis absorption spectroscopy.Similarly,compared with tiopronin and citrate-protected Ag nanoparticles,the zwitterionic phosphorylcholine Ag nanopar-ticles did not precipitate out of solution when charged polyelectrolytes or biopolymers were added.The zwitterionic phosphorylcholine might be a better ligand for stabilizing metal nanoparticles.
基金financially supported by the National Natural Science Foundation of China (21004048, 20974087)the Natural Science Foundation of Shaanxi Educational Committe (2010JK886)the Science Foundation of Northwest University (NF0912)
文摘In this work, the biocompatibility of a biomimetic, fully biodegradable ionomer phosphorylcholine (PC)-functionalized poly(butylene succinate) (PBS-PC) was investigated by means of hemolysis, platelet adhesion, protein adsorption and cytotox- icity experiments. The reference materials were poly(butylene succinate) (PBS) and chloroethylphosphoryl functionalized poly(butylene succinate) (PBS-Cl). The hemolysis rates (HR) of the leaching solutions of PBS, PBS-Cl and PBS-PC were all lower than the safe value, and the rate of PBS-PC was reduced to 1.07%. Scanning electron microscopy (SEM) measurements showed that platelet adhesion and aggregation were significant on both PBS and PBS-Cl surface. In contrast, very few platelets were observed on PBS-PC surface. Bicinchoninic acid (BCA) measurements revealed that the adsorption amounts of bovine serum albumin (BSA) and bovine plasma fibrinogen (BPF) on PBS-PC surface were 52% and 72% reduction respectively compared with those on PBS surface. Moreover, non-cytotoxicity of both PBS-PC particles and its leaching solution was sug- gested by MTT assay using mouse L929 fibroblast cells. All the results demonstrated that the biocompatibility of PBS could be greatly improved by PC end-capping strategy. This PC functionalized polyester may have potential applications in biological environments as a novel carrier for controlled drug release and scaffold for tissue engineering.
基金support by the National Natural Science Foundation of China(51503126,21534008,51573110)Scientific Research Foundation for Young Teachers of Sichuan University(2015SCU11005)Miaozi Project in Science and Technology Innovation Program of Sichuan Province(2016087).
文摘Zwitterionic materials are now widely used to fabricate various functionalized surfaces for biomedical applications due to their excellent non-fouling properties.However,a newly-discovered zwitterionic material,choline phosphate(CP),was reported to be cell-adhesive,which makes it different from traditional non-fouling zwitterionic materials such as sulfobetaine,carboxybetaine and phosphorylcholine(PC).To further investigate the properties of CP,a comparative study was conducted and the widely-reported zwitterionic PC was employed as a control which has the same chemical component but opposite orientation of charged groups with CP.For this purpose,CP and PC-functionalized surfaces were prepared by surface-initiated atom transfer radical polymerization(Si-ATRP),and their non-fouling properties were probed by protein adsorption and eukaryotic cell adhesion measurement.Results showed that CP-functionalized surfaces exhibited almost equivalent amounts of adsorbed proteins to that of PC,but they were more beneficial to cells initial adhesion and further spreading in serum-free medium,indicating that CP had a promising prospect of application in tissue engineering.
文摘Inspired by nature,hydrophilic diblock brush copolymers containing both phosphorylcholine groups and poly(ethylene oxide)(PEO)side chains were synthesized by successive reversible addition-fragmentation chain transfer(RAFT)polymerization of the zwitterionic monomer 2-methacryloyloxyethyl phosphorylcholine(MPC)and the PEO-containing macromonomer poly(ethylene oxide)methyl ether methacrylate(PEOMEMA)for the first time.The lubricating effect of several diblock brush copolymers and one gradient copolymer of MPC and PEOMEMA was evaluated by tribological measurements in polydimethylsiloxane(PDMS)-glass and cartilage-glass systems which were placed in phosphate-buffered saline(PBS)solutions of the polymers.The best lubrication was provided by the diblock copolymer with a relatively long poly(2-methacryloyloxyethyl phosphorylcholine)(pMPC)block and the copolymer of gradient structure.The average dynamic coefficient of friction(COF)in the PDMS-glass system at a copolymer concentration of0.4 mg/mL was only 0.004-0.007,while COF values of the copolymers in the cartilage-glass system after 450 sliding cycles reached 0.06-0.07.The excellent lubrication effect of the diblock and gradient copolymers of MPC and PEOMEMA is attributed to hydration lubrication provided by pMPC synergistically combined with steric repulsion from PEOMEMA.Entrapment of diblock brush copolymers between sliding surfaces was sufficient to provide effective lubrication,thus enhancing the efficacy of the diblock brush copolymers as potential additives for intraarticular injections.
基金financially supported by the National Natural Science Foundation of China(No.50673063)Program for the New-Century Excellent Talents of Ministry of Education of China(NCET-08-0381)Sichuan Provincial Science Fund for Distinguished Young Scholars(09ZQ026-024)
文摘A series of fluorinated phosphatidylcholine polyurethane macromolecular additives were synthesized by solution polymerization using methylenebis（phylene isocyanates） （MDI） and 1,4-butanediol （BDO） as hard segments, a new phoshporycholine, 2-（2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-hexadecafluoro-10-（2-hydroxyethoxy）decyloxy） ethyl phosphorycholine （HDFOPC） as end-capper, and four polydiols, poly（tetramethylene glycol）s （PTMG）, polydimethylsiloxane （PDMS）, poly（1,6-hexyl-1,5-pentylcarbonate） （PHPC） and poly（propylene glycol） （PPG） as soft segments, respectively. The chemical structures of the synthesized polyurethanes were characterized by 1H-NMR and FTIR. DSC and DMA were employed to study the phase behavior of these novel polyurethanes due to their great influences on the surface properties, and hence their interactions with bio-systems. The results showed that phase separation of the fluorinated phosphatidylcholine end-capped polyurethanes was increased in comparison with that of normal polyurethanes. The effect of fluorinated phosphatidylcholine end-capped groups on the phase behavior was further demonstrated by analyzing the degree of hydrogen-bonding between hard and soft segments.
基金supported by the National Natural Science Foundation of China(Nos.20774073,20974087)the Science and Technology Project of Shaanxi Province(No.2010K09-04)
文摘The surface design used for improving biocompatibility is one of the most important issues for the fabrication of medical devices. For mimicking the ideal surface structure of cell outer membrane, a large number of polymers bearing phosphorylcholine （PC） groups have been employed to modify the surfaces of biomaterials and medical devices. It has been demonstrated that the biocompatibility of the modified materials whose surface is required to interact with a living organism has been obviously improved by introducing PC groups. In this review, the fabrication strategies of cell outer membrane mimetic surfaces and their resulted biocompatibilities were summarized.
文摘Some Pseudomonas syringae pathovars secrete tabtoxin, a monocyclic β-lactam antibiotic, responsible for chlorosis, the principal halo blight symptom in susceptible plants as oats, rye, barley, wheat and sorghum, among other. Here, we demonstrated that the production of tabtoxin in a P. syringae strain increased at least 150%, when choline, betaine or dimethylglycine were used as nitrogen source, or when choline was added as osmoprotectant in hyperosmolar culture media. Besides, we investigated the induction of phosphorylcholine phosphatase (PchP) activity when choline or its metabolites were used as nitrogen sources. PchP is an enzyme involved in Pseudomonas aeruginosa pathogenesis through its contribution to the breakdown of choline-containing compounds of the host cells. Considering these results and that the success of a pathogenic microorganism depends on its ability to survive and proliferate in its target tissue, we propose that choline is one of the plant signals that contribute to establishment of the infection by tabtoxin-producing strains of P. syringae.
基金supported by project funding:Peking Medical Research Institute No.2023-5
文摘Background Although flow diverter device(FDD)has brought revolutionized advances in endovascular treatment of intracranial aneurysms,it also presents considerable drawbacks as well,as the innovation for novel device has never stopped.This preclinical research aims to evaluate the safety and efficacy of a newly developed FDD,the EMBOPIPE,through in vivo and in vitro experiments.Methods Aneurysms were induced in 20 New Zealand white rabbits which were randomized to three follow-up groups according to the time elapsed after EMBOPIPE implantation(28,90,and 180 days).Additional EMBOPIPEs were implanted in the abdominal aorta to cover the renal artery in nine rabbits.Angiography was performed immediately after device placement in all groups.Aneurysm occlusion,patency of renal arteries,and pathological outcomes were assessed.For the in vitro experiments,we measured the thrombogenic potential of EMBOPIPEs(n=5)compared with bare stents(n=5)using the Chandler loop model.Evaluation indicators were the platelet counts,macroscopic observations and scanning electron microscopy.Results EMBOPIPEs were successfully deployed in 19 of 20 rabbit aneurysms(95.0%).The rates of complete or near-complete aneurysm occlusion were 73.3%,83.3%,and 100%in the 28-,90-,and 180-day groups,respectively.All renal arteries covered by EMBOPIPEs remained patent,and the mean difference in renal artery diameter before and after the device placement in the three groups was 0.07 mm,0.10 mm,and 0.10 mm,respectively(p=0.77).Renal pathology was normal in all cases.The pathological findings of the aneurysms were as follows:thickened and adequate neointimal coverage at the aneurysm neck,minimal inflammatory response,near-complete smooth muscle cell layer,and endothelialization along the device.In vitro experiments showed that the platelet counts were significantly higher in EMBOPIPE blood samples than in bare stent samples and that platelet adhesion to the device was lower in the EMBOPIPE stent struts compared with bare stent struts through macroscopic observations and scanning electron microscopy.Conclusions The EMBOPIPE can achieve high rates of aneurysm occlusion while maintaining excellent branch artery patency.It exhibited wonderful pathological results.This novel device with phosphorylcholine surface modification could reduce platelet thrombus attached to the stent struts.
基金The authors gratefully acknowledge the financial support of the National Basic Research Program of China （Grant No. 2012CB619100） and the National Natural Science Foundation of China （Grant Nos. 51372087, 51232002, and 51072055）.
文摘Modification of biomaterials surface by mimetic cell membrane for improving biocompatibility, to imitate the excellent biological and physiological proper- ties of the natural cell membrane, is an important research area in materials science. Numerous studies have been attempted to construct a mimetic cell membrane biointer- face composed of phosphorylcholine （PC）-containing polymers or other phospholipid analogues on biomaterials surface. PC-containing biointerfaces show outstanding characteristics, especially in biological aspects such as blood compatibility and antifouling property. In this mini-review, the strategies of membrane mimetic modification of biomaterials and their antifouling applications are summarized.
基金financially supported by Program for New Century Excellent Talents in University“NCET”,Ministry of Education of Chinathe International Cooperation from Ministry of Science and Technology of China(Grant No.2008DFA51170)sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education of China.
文摘Thrombus formation and blood coagulation are serious problems associated with blood contacting products,such as catheters,vascular grafts,artificial hearts,and heart valves.Recent progresses and strategies to improve the hemocompatibility of biomaterials by surface modification using photochemical immobilization and photograft polymerization are reviewed in this paper.Three approaches to modify biomaterial surfaces for improving the hemocompatibility,i.e.,bioinert surfaces,immobilization of anticoagulative substances and biomimetic surfaces,are introduced.The biomimetic amphiphilic phosphorylcholine and Arg-Gly-Asp(RGD)sequence are the most effective and most often employed biomolecules and peptide sequence for improving hemocompatibility of material surfaces.The RGD sequence can enhance adhesion and growth of endothelial cells(ECs)on material surfaces and increase the retention of ECs under flow shear stress conditions.This surface modification is a promising strategy for biomaterials especially for cardiovascular grafts and functional tissue engineered blood vessels.
基金financially supported by the National Natural Science Foundation of China(52022043 and 21868011)Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program(20191080593)+2 种基金Precision Medicine Foundation,Tsinghua University,China(10001020107)the National Key R&D Program of China(2017YFC1103800)Research Fund of State Key Laboratory of Tribology,Tsinghua University,China(SKLT2022C18).
文摘Osteoarthritis is associated with the significantly increased friction of the joint,which results in progressive and irreversible damage to the articular cartilage.A synergistic therapy integrating lubrication enhancement and drug delivery is recently proposed for the treatment of early-stage osteoarthritis.In the present study,bioinspired by the self-adhesion performance of mussels and super-lubrication property of articular cartilages,a biomimetic self-adhesive dopamine methacrylamide-poly(2-methacryloyloxyethyl phosphorylcholine)(DMA-MPC)copolymer was designed and synthesized via free radical polymerization.The copolymer was successfully modified onto the surface of biodegradable mesoporous silica nanoparticles(bMSNs)by the dip-coating method to prepare the dual-functional nanoparticles(bMSNs@DMA-MPC),which were evaluated using a series of surface characterizations including the transmission electron microscope(TEM),Fourier transform infrared(FTIR)spectrum,thermogravimetric analysis(TGA),X-ray photoelectron spectroscopy(XPS),etc.The tribological test and in vitro drug release test demonstrated that the developed nanoparticles were endowed with improved lubrication performance and achieved the sustained release of an anti-inflammatory drug,i.e.,diclofenac sodium(DS).In addition,the in vitro biodegradation test showed that the nanoparticles were almost completely biodegraded within 10 d.Furthermore,the dual-functional nanoparticles were biocompatible and effectively reduced the expression levels of two inflammation factors such as interleukin-1β(IL-1β)and interleukin-6(IL-6).In summary,the surface functionalized nanoparticles with improved lubrication and local drug release can be applied as a potential intra-articularly injected biolubricant for synergistic treatment of early-stage osteoarthritis.
基金supported by the National Natural Science Foundation of China(Grant Nos.51673146,51673144 and 51773151).
文摘The synergistic effect of polyethylene glycol(PEG)and poly(2-methacry-loyloxyethyl phosphorytcholine)(PMPC)can effectively reduce the protein absorption,which is beneficial to theranostics.However,PEG-PMPC-based polymers have rarely been used as nanocarriers in the theranostic field due to their limited modifiability and weak interaction with other materials.Herein,a plain method was proposed to endow them with the probable ability of loading small active agents,and the relationship between the structure and the ability of loading hydrophobic agents was explored,thus expanding their applications.Firstly,mPEG-PMPC or 4-arm-PEG-PMPC polymer was synthesized by atom transfer radical polymerization(ATRP)using mPEG-Br or 4-arm-PEG-Br as the macroinitiator.Then a strong hydrophobic segment,poly(butyl methacrylate)(PBMA),was introduced and the ability to load small hydrophobic agents was further explored.The results showed that linear mPEG-PMPC-PBMA could form micelles 50-80 nm in size and load the hydrophobic agent such as Nile red efficiently.In contrast,star-like 4-arm-PEG-PMPC-PBiyiA,a monomolecular micelle(10-20 nm),could hardly load any hydrophobic agent.This work highlights effective strategies for engineering PEG-PMPC-based polymers and may facilitate the further application in numerous fields.
