Graft Copolymerization of N,N-Dimethylacrylamide to Cellulose in Homogeneous Media Using Atom Transfer Radical Polymerization for Hemocompatibility

In homogeneous media, N,N-Dimethylacrylamide (DMA) was grafted copolymerization to cellulose by a metal-catalyzed atom transfer radical polymerization (ATRP) process. First, cellulose was dissolved in DMAc/LiCl system, and it reacted with 2-bromoisobutyloyl bromide (BiBBr) to produce macroinitiator (cell-BiB). Then DMA was polymerized to the cellulose backbone in a homogeneous DMSO solution in presence of the cell-BiB. Characterization with FT-IR, NMR, and GPC measurements showed that there obtained a graft copolymer with cellulose backbone and PDMA side chains (cell-PDMA) in well-defined structure. The proteins adsorption studies showed that the cellulose membranes modified by the as-prepared cell-PDMA copolymer owns good protein adsorption resistancet.

Relationship and improvement strategies between drug nanocarrier characteristics and hemocompatibility:What can we learn from the literature

This article discusses the various blood interactions that may occur with various types of nano drug-loading systems. Nanoparticles enter the blood circulation as foreign objects. On the one hand, they may cause a series of inflammatory reactions and immune reactions, resulting in the rapid elimination of immune cells and the reticuloendothelial system, affecting their durability in the blood circulation. On the other hand, the premise of the drug-carrying system to play a therapeutic role depends on whether they cause coagulation and platelet activation, the absence of hemolysis and the elimination of immune cells. For different forms of nano drug-carrying systems, we can find the characteristics, elements and coping strategies of adverse blood reactions that we can find in previous researches. These adverse reactions may include destruction of blood cells, abnormal coagulation system, abnormal effects of plasma proteins, abnormal blood cell behavior, adverse immune and inflammatory reactions, and excessive vascular stimulation. In order to provide help for future research and formulation work on the blood compatibility of nano drug carriers.

Hemocompatibility of Albumin Nanoparticles as a Drug Delivery System—An in Vitro Study

As a major plasma protein, albumin has a distinct advantage compared with other materials for nanoparticle preparation. It is cheap and easily available. The present work aimed to prepare bovine albumin nanoparticles (BAN) with a simple coacervation method and to test their hemocompatibility. The albumin nanoparticles obtained by this method had a range of sizes from 250 - 350 nm at pH = 7.4. In vitro hemocompatibility tests of the prepared (BAN) were conducted after the incubation of BAN with normal blood for 2 h at 37&degC. Hemocompatibility tests showed that the reduction in the hemolysis percentage of erythrocytes was due to exposure to BAN. The other blood parameters such as hemoglobin (HG), mean corpuscle hemoglobin (MCH), and mean corpuscle hemoglobin concentration (MCHC) were in the normal range. The prothrombin time (PT) and erythrocyte sedimentation rate (ESR) decreased as the concentration of BAN increased. The results obtained in this study demonstrated that BAN could be used safely and without abnormal effect when interacted with blood through many biomedical applications.

Effect ofβ-cyclodextrin on the hemocompatibility of heparin-modified PMP hollow fibrous membrane for Extracorporeal Membrane Oxygenation(ECMO)

In this paper,modified membranes containingβ-cyclodextrin(β-CD)and heparin coatings were prepared on the surface of poly-4-methyl-1-pentene(PMP)hollow fibrous membrane using the high strength adhesion of polydopamine(PDA).In this paper,β-CD was added to increase the hemocompatibility of the PMP hollow fibrous membranes and the stability of the heparin coating.The uniformity of the heparin coating withβ-CD addition was better than that of the groups withoutβ-CD.After seven days of saline rinsing,the surface of the modified membranes withβ-CD addition still had a large amount of heparin present,which was more stable compared to the control group.After surface modification,the modified membrane changed from hydrophobic to hydrophilic.Importantly,the protein adsorption,platelet adhesion,and hemolysis rates of the modified membranes were significantly reduced compared with the pristine membranes.The APTT values were also significantly increased.The results showed that the modified membranes with the addition ofβ-CD had better hydrophilicity,can maintain the stability of heparin coating for a long time,and finally showed good hemocompatibility.

Polydopamine/poly(sulfobetaine methacrylate)Co-deposition coatings triggered by CuSO_(4)/H_(2)O_(2)on implants for improved surface hemocompatibility and antibacterial activity

Implanted biomaterials such as medical catheters are prone to be adhered by proteins,platelets and bacteria due to their surface hydrophobicity characteristics,and then induce related infections and thrombosis.Hence,the development of a versatile strategy to endow surfaces with antibacterial and antifouling functions is particularly significant for blood-contacting materials.In this work,CuSO_(4)/H_(2)O_(2)was used to trigger polydopamine(PDA)and poly-(sulfobetaine methacrylate)(PSBMA)co-deposition process to endow polyurethane(PU)antibacterial and antifouling surface(PU/PDA(Cu)/PSBMA).The zwitterions contained in the PU/PDA(Cu)/PSBMA coating can significantly improve surface wettability to reduce protein adsorption,thereby improving its blood compatibility.In addition,the copper ions released from the metal-phenolic networks(MPNs)imparted them more than 90%antibacterial activity against E.coli and S.aureus.Notably,PU/PDA(Cu)/PSBMA also exhibits excellent performance in vivo mouse catheter-related infections models.Thus,the PU/PDA(Cu)/PSBMA has great application potential for developing multifunctional surface coatings for blood-contacting materials so as to improve antibacterial and anticoagulant properties.

Surface modification of biomaterials by photochemical immobilization and photograft polymerization to improve hemocompatibility

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.

Effects of COOH^+ ion implantation on hemocompatibility of polypropylene

Carboxyl ion (COOH+) implantation was performed at 50 keV with different fluences for polypropylene. Hemocompatibility tests show that blood coagulation time and recalcification time of polypropylene were enhanced significantly with the increasing fluence. At the same time, the human endothelial cells grown on the surface of the implanted samples exhibited normal cellular growth and morphology. X-ray photoelectron spectroscopy and water contact angle analysis showed that COOH+ ion implantation rearranges chemical bonds and produces some new polar O-containing groups on the surface. The formation of polar functional groups, together with increase of roughness, induced an increase in hydrophilicity, which in turn improved the surface hemocompatibility of polypropylene.

Cu^(Ⅱ)-loaded polydopaminecoatingswith in situ nitric oxidegenerationfunctionforimproved hemocompatibility

NO is the earliest discovered gas signal molecule which is produced by normal healthy endothelial cells,and it has many functions,such as maintaining cardiovascular homeostasis,regulating vasodilation,inhibiting intimal hyperplasia and preventing atherosclerosis in the blood system.Insufficient NO release is often observed in the pathological environment,for instance atherosclerosis.It was discovered that NO could be released from the human endogenous NO donor by many compounds,and these methods can be used for the treatment of certain diseases in the blood system.In this work,a series of copper-loaded polydopamine(PDA)coatings were produced through self-polymerization time for 24,48 and 72 h.The chemical composition and structure,coating thickness and hydrophilicity of the different copper-loaded PDA coatings surfaces were characterized by phenol hydroxyl quantitative,X-ray photoelectron spectroscopy,ellipsometry atomic force microscopy and water contact angles.The results indicate that the thickness and the surface phenolic hydroxyl density of the PDA coatings increased with the polymerization time.This copperloaded coating has glutathione peroxidase-like activity,and it has the capability of catalyzing NO releasing from GSNO.The surface of the coating showed desirable hemocompatibility,the adhesion and activation of platelets were inhibited on the copper-loaded coatings.At the same time,the formation of the thrombosis was also suppressed.These copper-loaded PDA coatings could provide a promising platform for the development of blood contact materials.

Theoretical calculation and experimental study of influence of oxygen vacancy on the electronic structure and hemocompatibility of rutile TiO_2

In this work,the relationship between electronic structure and hemocompatibility of oxygen deficient rutile TiO2-x was studied by both theoretical calculation and experimental study. Based on the local density functional theory,first-principals method was performed to calculate the electronic structure of rutile TiO2 with different oxygen vacancy concentration. In the range of less than 10% of (or equal) physically realistic O vacancy concentration,the band gap of rutile TiO2 increases with increasing O vacancy concentration,leading the TiO2 changes from a p-type to an n-type semiconductor. The valance band of TiO2 is predominated by O 2p orbital,while the conduction band is occupied by Ti 3d orbital for different O vacancy concentration. The O vacancy results in the occupation of electrons at the bottom of conduction band of TiO2,and the donor density increases with increasing O vacancy concentration. When materials come in contact with blood,the n-type semiconductor feature of oxygen deficient TiO2-x with the bottom of conduction band occupied by electrons would prevent charge transfer from fibrinogen into the surface of materials,thus inhibiting the aggregation and activation of platelets,therefore improving the hemocompatibility of rutile TiO2-x.

Hemocompatibility of DLC coatings synthesized by ion beam assisted deposition

Ion beam-assisted diamond-like carbon (DLC) coatings have beenused for growing the human platelet, fibrinogen, and albumin in the control environment in order to assess their hemocompatibility. The hard carbon films were prepared on polymethylmethacrylate (PMMA) at room temperature using ion beam assisted deposition (IBAD). Raman spectroscopic analysis proved that the carbon films on PMMA are diamond-like with a higher fraction of sp\+3 bonds in the structure of mixed sp\+2+sp\+3 bonding. The blood protein adsorption tests showed that DLC coatings can adsorb more albumin and are slightly more fibrinogen than the PMMA chosen as a control sample. The platelets adhered on DLC coatings were reduced significantly in number. These results indicate good hemocompatibility of DLC coatings.

Fabrication of chitosan/silica hybrid coating on AZ31 Mg alloy for orthopaedic applications

Biocompatible conversion of chitosan and chitosan/silica hybrid coating were prepared to enhance the biocompatibility and corrosion resistance of biodegradable AZ31 Mg alloy. The coatings were optimized and analysed with potentiodynamic polarization, SEM, ATR-IR and XPS studies. Potentiodynamic polarization studies, revealed that the coatings exhibited high corrosion resistance. The surface morphology of the Ch-3/Si coating showed small globular rough structure. The presence of functional groups was confirmed by ATR-IR. For a better understanding of chitosan/silica hybrid coating, the chemical states were examined by XPS studies. The in-vitro bioactivity of the coated samples was evaluated in Earle’s solution, which formed a dense layer of coral-like structure and calcium-deficient apatite with less stoichiometric ratio than the hydroxyapatite. In-vitro cell culture studies exhibited a good cell proliferation rate and the fabricated Ch-3/Si coating was found to be non-hemolytic. The bacterial studies proved that Ch-3/Si coating possessed inherent antibacterial activity.

The facile method developed for preparing polyvinylidene fluoride plasma separation membrane via macromolecular interaction

The design of membrane pore is critical for membrane preparation. Polyvinylidene fluoride(PVDF) membrane exhibits outstanding properties in the water-treatment field. However, it is a huge challenge to prepare PVDF macro-pore plasma separation membrane by non-solvent induced phase separation(NIPS). Herein, a facile strategy is proposed to prepare PVDF macro-pore plasma separation membrane via macromolecular interaction. ATR-FTIR and ^(1)H NMR showed that the intermolecular interaction existed between polyethylene oxide(PEO) and polyvinylpyrrolidone(PVP). It could significantly affect the PVDF macro-pore membrane structure. The maximum pore of the PVDF membrane could be effectively adjusted from small-pore/medium-pore to macro-pore by changing the molecular weight of PEO. The PVDF macro-pore membrane was obtained successfully when PEO-200 k existed with PVP. It exhibited higher plasma separation properties than the currently used plasma separation membrane.Moreover, it had excellent hemocompatibility due to the similar plasma effect, hemolysis, prothrombin time, blood effect and complement C_(3a) effect with the current utilized plasma separation membrane,implying its great potential application. The proposed facile strategy in this work provides a new method to prepare PVDF macro-pore plasma separation membrane by NIPS.

Preparation of functional coating on magnesium alloy with hydrophilic polymers and bioactive peptides for improved corrosion resistance and biocompatibility

Biodegradable magnesium alloy stents(MAS)have great potential in the treatment of cardiovascular diseases.However,too fast degradation and the poor biocompatibility are still two key problems for the clinical utility of MAS.In the present work,a functional coating composed of hydrophilic polymers and bioactive peptides was constructed on magnesium alloy to improve its corrosion resistance and biocompatibility in vitro and in vivo.Mg-Zn-Y-Nd(ZE21B)alloy modified with the functional coating exhibited moderate surface hydrophilicity and enhanced corrosion resistance.The favourable hemocompatibility of ZE21B alloy with the functional coating was confirmed by the in vitro blood experiments.Moreover,the modified ZE21B alloy could selectively promote the adhesion,proliferation,and migration of endothelial cells(ECs),but suppress these behaviors of smooth muscle cells(SMCs).Furthermore,the modified ZE21B alloy wires could alleviate intimal hyperplasia,enhance corrosion resistance and re-endothelialization in vivo transplantation experiment.These results collectively demonstrated that the functional coating improved the corrosion resistance and biocompatibility of ZE21B alloy.This functional coating provides new insight into the design and development of novel biodegradable stents for biomedical engineering.

Bioreactivity of Stent Material: <i>In Vitro</i>Impact of New Twinning-Induced Plasticity Steel on Platelet Activation

A current challenge concerns developing new bioresorbable stents that combine optimal mechanical properties and biodegradation rates with limited thrombogenicity. In this context, twinning-induced plasticity (TWIP) steels are good material candidates. In this work, the hemocompatibility of a new TWIP steel was studied in vitro via hemolysis and platelet activation assessments. Cobalt chromium (CoCr) L605 alloy, pure iron (Fe), and magnesium (Mg) WE43 alloy were similarly studied for comparison. No hemolysis was induced by TWIP steel, pure Fe, or L605 alloy. Moreover, L605 alloy did not affect CD62P exposure, αIIbβ3 activation at the platelet surface, or phosphorylation of protein kinase C (PKC) substrates upon thrombin stimulation. In contrast, TWIP steel and pure Fe significantly decreased platelet response to the agonist. Given that similar inhibitory effects were obtained when using a conditioned medium previously incubated with TWIP steel, we postulated TWIP steel corrosion to be likely to release components counteracting platelet activation. We showed that the main ion form present in the conditioned medium is Fe3+. In conclusion, TWIP steel resorbable scaffold displays anti-thrombogenic properties in vitro, which suggests that it could be a promising platform for next-generation stent technologies.

<i>In Vivo</i>Pharmacokinetic and Hemocompatible Evaluation of Lyophilization Induced Nifedipine Solid-Lipid Nanoparticle

Nifedipine-solid-lipid nanoparticles lyophilized with trehalose (NI-SLN-Tre) were prepared by the high pressure homogenization of a roll mixture consisting of NI and hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol, and in vivo pharmacokinetic properties and their hemocompatibility were determined and compared with those of a NI-SLN suspension. The resulting pharmacokinetic data demonstrated that although no significant differences were observed between the time of peak concentration (Tmax), peak plasma concentration (Cmax), and the area under the curve (AUC0→∞) values of both administrated samples, NI tended to be absorbed to a much greater extent from the lyophilized NI-SLN-Tre suspensions because of the enhanced solvation of NI-SLN in gastrointestinal fluid, derived from formation of hydrogen bonds between the polar head groups of the lipids and the O-H groups of trehalose. Furthermore, the results of a hemolysis assay revealed that the NI-SLN and NI-SLN-Tre suspensions showed good hemocompatibility properties with hemolysis values of less than 5%. Taken together, the results of this study demonstrate that NI-SLN-Tre exhibits suitable pharmacokinetic properties and good biocompatibility.

Advanced hemocompatible polyethersulfone composite artificial lung membrane with efficient CO_(2)/O_(2)exchange channel constructed by modified carbon nanotubes network

Artificial lung membranes as the core module of the extracorporeal membrane oxygenation technology(ECMO)execute the function of extracorporeal blood-gas barrier accomplishing CO_(2)/O_(2)exchange with blood.However,the unsatisfactory hemocompatibility and difficulty in functionalization are the promi-nent challenges faced by current artificial lung membrane materials.In this study,polyethersulfone(PES)composite membranes with self-anticoagulant property and high gas exchange efficient are fabricated by blending PES matrix with poly(vinylamine)(PVAm)modified carboxylic carbon nanotubes(mCNTs)and citrate-based poly(octamethylene-citrate)(POC)pre-polymers.The mCNTs construct specific gas transfer channels within the composite membranes to enhance the gas permeability,while the POC pre-polymers provide anticoagulant property based on the chelation to blood Ca^(2+)and the inactivation effect to in-trinsic coagulation factors.Importantly,directed by the actual ECMO gas exchange mode,we design a gas-liquid convectional circulation device that could evaluate gas exchange efficiency for the composite membranes under mimetic ECMO state.Therefore,this strategy not only proposes a new design method of advanced artificial lung membranes to solve the practical challenges in the current ECMO technology,but also establishes a scientific testing method to evaluate the gas exchange performance for new-type artificial lung membrane materials in the future.

Incorporation of Lysine-Containing Copolymer with Polyurethane Affording Biomaterial with Specific Adsorption of Plasminogen

新奇 biomaterial 通过包含离氨酸的共聚物的物理加入基于聚氨酯(PU ) 被准备改进它的 hemocompatibility 和 plasminogen 的表面识别。包含离氨酸的共聚物经由 2-ethylhexyl methacrylate ( EHMA )的 copolymerization 被综合， oligo (乙烯乙二醇)甲基醚 methacrylate ( OEGMA )和 6-tert-butoxycarbonyl amino-2-( 2-methyl-acryloylamino ) -hexanoic 酸tert丁基酉旨( Lys (P)麻省)，在共聚物在离氨酸残余上由 COOH 和 -NH2 组的 deprotection 列在后面。共聚物的作文能被改变单体调整喂比率。三个部件贡献分别地与 PU，到 nonspecific 蛋白质吸附的抵抗和 plasminogen 的特定的绑定改进相容性。向 plasminogen 的有约束力的能力在共聚物与离氨酸内容增加了。这条途径与改进 hemocompatibility 和特定的 biomolecules 的表面识别为新奇 biomaterials 的产生说明一个简单方法。

Hemocompatible polyurethane/gelatin-heparin nanofibrous scaffolds formed by a bi-layer electrospinning technique as potential artificial blood vessels

In this paper,a scaffold,which mimics the morphology and mechanical properties of a native blood vessel is reported.The scaffold was prepared by sequential bi-layer electrospinning on a rotating mandrel-type collector.The tubular scaffolds(inner diameter 4 mm,length 3 cm)are composed of a polyurethane(PU)fibrous outer-layer and a gelatin-heparin fibrous inner-layer.They were fabricated by electrospinning technology,which enables control of the composition,structure,and mechanical properties of the scaffolds.The microstructure,fiber morphology and mechanical properties of the scaffolds were examined by means of scanning electron microscopy(SEM)and tensile tests.The PU/gelatinheparin tubular scaffolds have a porous structure.The scaffolds achieved a breaking strength(3.7±0.13 MPa)and an elongation at break(110±8%)that are appropriate for artificial blood vessels.When the scaffolds were immersed in water for 1 h,the breaking strength decreased slightly to 2.2±0.3 MPa,but the elongation at break increased to 145
21%.In platelet adhesion tests the gelatin-heparin fibrous scaffolds showed a significant suppression of platelet adhesion.Heparin was released from the scaffolds at a fairly uniform rate during the period of 2nd day to 9th day.The scaffolds are expected to mimic the complex matrix structure of native arteries,and to have good biocompatibility as an artificial blood vessel owing to the heparin release.

In vitro and in vivo Evaluation of TONGXIN LVAD

Background: Tongxin left ventricular assist device(LVAD), an implantable magnetic suspending VAD developed in China Heart Biomedical Incorporation aiming for clinical use, weighs about 350 g and can deliver 6 L/min for pressures of 145 mmHg at 2500 rpm. Objective: This study aims to investigate the implantation possibility, hemolysis and hemocompatibility of the LVAD before clinic use. Methods: The tests of implantation possibility, hemolysis and hemocompatibility to the LVAD were completed by fitting study, hemolysis test and in vivo experiments respectively. Meanwhile the hemolysis was evaluated by the amount of free hemoglobin in plasma and studied using the normalized index of hemolysis(NIH). Results: The fitting study showed that the blood pump could be implanted in the sheep heart chambers without squeezing the surrounding organs by comparing the preoperative and the postoperative chest X-ray. The NIH value of Tongxin LVAD was(0.00750±0017) g/100 L in vitro hemolysis test. Two sheep in vivo experiments showed the hemolysis in vivo was below 7.5 mg/dL. Hematologic and biochemical test results were within normal limits during the study period. There were no significant complications. Postmortem examination of the explanted organs revealed no evidence of microemboli, ischemia or infarction. The pump's inflow and outflow conduits were free of thrombus. Conclusion:These results indicated that the implantable magnetic suspending LVAD showed exceptional implantation possibility, hemolysis and hemocompatibility, which are crucial to the clinical success of this implantable LVAD.