Cell outer membrane mimetic modification of a cross-linked chitosan surface to improve its hemocompatibility

A novel strategy has been developed to improve the hemocompatibility of chitosan surface by cell outer membrane mimetic structure able to reduce protein adsorption and cell adhesion. Phosphorylcholine dichloride was synthesized and grafted onto a glutaraldehyde-cross-linked chitosan (CS-GA) film surface to prepare phosphorylcholine-coated CS-GA film (CS-GA-PC) through a heterogeneous reaction process. The spectroscopic and contact angle characterization show that a cell outer membrane mimetic structure was formed on the cross-linked chitosan surface, and the significantly improved hemocompatibility of the modified surface was shown by a suppression of 94% on platelet adhesion, a suppression of 60–70% for bovine plasma fibrinogen and bovine serum albumin adsorptions. These results demonstrated that this cell outer membrane mimetic surface modification with phosphorylcholine dichloride is a promising strategy to improve the hemocompatibility of chitosan.     

Structural Element of Vitamin U-Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections

Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium-based polypeptides with different degrees of branching and polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G₂-PM-1^H+, shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in “Angew. Chem. Int. Ed., 2020, 59, 6412.”), which can be attributed to the high positive charge density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G₂-PM-1^H+ are primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram-positive or gram-negative bacteria in a mixed-bacteria model. Additionally, both in vitro and in vivo experiments demonstrated that G₂-PM-1^H+ exhibited superior efficacy against methicillin-resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G₂-PM-1^H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.     

Enhancing the blood compatibility of ion-selective electrodes

In vivo monitoring of various analytes is important for many bioanalytical and biomedical applications. The crucial challenge in this type of applications is the interaction of the sensor with the host environment, which is qualitatively described by the term biocompatibility. This review discusses recent advances in methods and materials used for the improvement of the biocompatibility of ion-selective electrodes especially as it relates to their interaction with blood components.     

Development of lauroyl sulfated chitosan for enhancing hemocompatibility of chitosan

Chitosan (CS) has received much attention as a functional biopolymer especially in pharmaceutical applications, but has serious limitations owing to its poor hemo-compatibility property. Present paper focuses on the chemical modification of CS in order to enhance hemocompatibility. Amphiphilic derivative (lauroyl sulfated chitosan, LSCS) was prepared by the inclusion of sulfo group (hydrophilic) and lauroyl group (hydrophobic) to CS backbone and particles were prepared by an ionic-gellation approach. Modification was confirmed by FTIR, NMR and zeta potential measurements and the microparticles were evaluated for its particle size, swelling properties and thermal behaviour. Blood compatibility studies like hemolysis, RBC, WBC, platelet aggregation studies, blood clotting time, protein adsorption and C3 protein depletion assay were carried out for these polymers using standard techniques and cytotoxicity studies were performed to understand its applicability. Negatively charged (-6.06 mV) LSCS submicroparticles (886 nm) were prepared in this study. Blood compatibility studies demonstrated that the amphiphilic modification improved the hemocompatibility of CS. RBC aggregation and hemolysis induced by CS were significantly reduced by this modification. Further amphiphilic modification was effective in reducing the protein adsorption on CS. LSCS derivatives were found to be non-toxic in L929 cell lines. From these studies, it appears that LSCS is a hemocompatible version of CS.     

Influence of Plasma Treatments on the Hemocompatibility of PET and PET + TiO<Subscript>2</Subscript> Films

A dielectric barrier discharge (DBD) in helium was used to ameliorate the interface between the blood and the surface of polymeric implants: polyethylene terephthalate (PET) and PET with titanium oxide (PET + TiO₂). A higher crystallinity degree was found for the DBD treated samples. The wettability of polymers was improved after the treatment. The chemical composition, analyzed by infrared spectroscopy was preserved during the DBD treatment. The surface modifications have been correlated with polymers hemocompatibility. Concerning the polymer surface–blood interaction, the treatment induced a decrease of the interfacial tension between the blood components and the treated surfaces. The in vitro tests of hemocompatibility showed no perturbation in the blood composition when the polymer samples are present in the blood volume. An interesting result is related to the whole blood clotting time that shows a dramatic increase on the treated surfaces. Moreover, the coagulation kinetics on the treated surfaces is modified.     

IgA肾病免疫吸附剂吸附性能及血液相容性研究

针对IgA肾病研究制备用于IgA吸附的免疫吸附剂．采用不同活化方法、不同配基制备吸附剂，测定吸附效率并进行比较．体外吸附实验表明吸附剂对IgA肾病病人血清中的IgA具有较强的吸附性能；对正常人血液进行血液相容性实验及对健康小鼠的急性毒性实验证明该吸附剂具有良好的血液相容性且安全、无毒．该吸附剂可作为IgA肾病的免疫吸附剂．     

羧基化氧化石墨烯的血液相容性

氧化石墨烯的官能团修饰可促进氧化石墨烯与生物体液、聚合物基体等不同环境的融合. 通过超声法制备了氧化石墨烯, 并利用化学改性的方法, 将氧化石墨烯表面的羟基和环氧基转变为羧基. 红外图谱上羧基化氧化石墨烯(GeneO-COOH)的羧基振动明显, 峰强增大. GeneO-COOH的主要失重表现为羧基官能团缩合以一个水分子的形态释放失去结构水[OH2]. 复钙动力学曲线随着GeneO-COOH的浓度增加, 曲线上升趋势由陡峭趋于平缓, 当浓度为1.25 μg/mL时复钙时间延长了11 min, 平台期OD值降低了8.14 %; 在0.5~100 μg/mL浓度范围内溶血率均<5 %. GeneO-COOH比GeneO在同等低浓度下的抗凝血性能有一定程度的改善, 主要是因为带负电的羧基可直接络合凝血因子. 因此, 羧基修饰氧化石墨烯是提高血液相容性的有效手段, 羧基化氧化石墨烯可作为潜在的生物医用材料的填料.     

Fluorinated siloxane-containing waterborne polyurethaneureas with excellent hemocompatibility, waterproof and mechanical properties

Two series of polyurethaneurea (PUU) aqueous dispersions consisting of fluorinated siloxane segments were prepared from a high-molecular-weight (M_n = 8361) α,ω-dihydroxypoly[(3,3,3-trifluoropropyl)methylsiloxane] (PTFPMS), dimethylolpropionic acid, isophorone diisocyanate and ethylenediamine, with poly (tetramethylene oxide) and polycarbonate polyols as soft segments, respectively. These anionic aqueous dispersions were stable at the ambient temperature for more than 6 months, with particle sizes ranging from 45 to 98 nm. Both series of PUU films showed the excellent waterproof properties, i.e. the decrease in water absorption and surface energy upon the incorporation of PTFPMS segments. The phase mixing increased in the fluorinated siloxane-containing polyether-based PUUs and the phase separation increased first then decreased in the fluorinated siloxane-containing polycarbonate-based PUUs, with increasing PTFPMS content. All the PTFPMS-modified PUU films showed excellent mechanical properties. The polycarbonate-based PUU film consisting of 5 wt.% PTFPMS had a tensile strength of 60.7 MPa and a breaking elongation of 632%, owing to the increase in the ordered hydrogen bonding degree and the microphase-separation degree between the hard and soft segments in the system. In vitro hemolysis and dynamic clotting time measurements indicated that the thromboresistance was enhanced markedly with increasing PTFPMS content for both series of PUUs, which could be ascribed to the synergistic effect between the carboxylate groups and the PTFPMS segments migrating onto the surfaces of the films.     

Novel perfluoroalkylated oligo(oxyethylene) methyl ethers with high hemocompatibility and excellent co-emulsifying properties for potential biomedical uses

Two series of novel perfluoroalkylated amphiphilic compounds were synthesized from monomethyl ethers of mono-, di- and tri-(oxyethylene) glycols. The first series CH₃(OCH₂CH₂)_nOCH₂CH(OH)CH₂-CF₂(CF₂CF₂)_nCF₃ (n = 1-3) bearing the hydroxy group at the spacer between hydrophilic and hydrophobic parts was prepared by the reactions of the monomethyl ethers with 2-(perfluoroalkylmethyl)oxiranes in 76-97% yields. The second series CH₃(OCH₂CH₂)_nOCH₂CH₂CH₂-CF₂(CF₂CF₂)_nCF₃ (n = 1-3) possessing the non-hydroxylated spacer was synthesized from allyl methyl ethers of oligo(oxyethylene) glycols using radical additions of perfluoroalkyl iodides and subsequent selective reductions of the C-I bond in the adducts in overall yields of 23-69%. Some of the novel amphiphilic compounds displayed very low hemolytic activity to erythrocytes and excellent co-emulsifying properties on testing on perfluorodecalin/Pluronic F-68 microemulsions. 1-O-(2-Hydroxy-4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluorononyl)-d-xylitol was prepared by a novelized synthesis and employed as a standard compound in the testing.     

A study of TaxC1−x coatings deposited on biomedical 316L stainless steel by radio-frequency magnetron sputtering

In this paper, Ta_xC_1−x coatings were deposited on 316L stainless steel (316L SS) by radio-frequency (RF) magnetron sputtering at various substrate temperatures (T_s) in order to improve its corrosion resistance and hemocompatibility. XRD results indicated that T_s could significantly change the microstructure of Ta_xC_1−x coatings. When T_s was <150 °C, the Ta_xC_1−x coatings were in amorphous condition, whereas when T_s was ≥150 °C, TaC phase was formed, exhibiting in the form of particulates with the crystallite sizes of about 15-25 nm (T_s = 300 °C). Atomic force microscope (AFM) results showed that with the increase of T_s, the root-mean-square (RMS) values of the Ta_xC_1−x coatings decreased. The nano-indentation experiments indicated that the Ta_xC_1−x coating deposited at 300 °C had a higher hardness and modulus. The scratch test results demonstrated that Ta_xC_1−x coatings deposited above 150 °C exhibited good adhesion performance. Tribology tests results demonstrated that Ta_xC_1−x coatings exhibited excellent wear resistance. The results of potentiodynamic polarization showed that the corrosion resistance of the 316L SS was improved significantly because of the deposited Ta_xC_1−x coatings. The platelet adhesion test results indicated that the Ta_xC_1−x coatings deposited at T_s of 150 °C and 300 °C possessed better hemocompatibility than the coating deposited at T_s of 25 °C. Additionally, the hemocompatibility of the Ta_xC_1−x coating on the 316L SS was found to be influenced by its surface roughness, hydrophilicity and the surface energy.