Bioinspired Zwitterionic Block Polymer-Armored Nitric Oxide-Generating Coating Combats Thrombosis and Biofouling.

Thrombosis and infection are 2 major complications associated with central venous catheters (CVCs), resulting in substantial mortality and morbidity. The concurrent long-term administration of antibiotics and anticoagulants to address these complications have been demonstrated to cause severe side effects such as antibiotic resistance and bleeding. To mitigate these complications with minimal or no drug utilization, we developed a bioinspired zwitterionic block polymer-armored nitric oxide (NO)-generating functional coating for surface modification of CVCs. This armor was fabricated by precoating with a Cu-dopamine (DA)/selenocysteamine (SeCA) (Cu-DA/SeCA) network film capable of catalytically generating NO on the CVCs surface, followed by grafting of a zwitterionic p(DMA-b-MPC-b-DMA) polymer brush. The synergistic effects of active attack by NO and copper ions provided by Cu-DA/SeCA network and passive defense by zwitterionic polymer brush imparted the CVCs surface with durable antimicrobial properties and marked inhibition of platelets and fibrinogen. The in vivo studies confirmed that the surface-armored CVCs could effectively reduce inflammation and inhibit thrombosis, indicating a promising potential for clinical applications.

Bioinspired Self-Adhesive Lubricated Coating for the Surface Functionalization of Implanted Biomedical Devices.

The lubrication property of implanted biomedical devices is of great significance as it affects the clinical performance owing to direct contact with soft tissues. In the present study, a bioinspired copolymer with dual functions of both self-adhesion and lubrication was synthesized with N-(3-aminopropyl) methacrylamide hydrochloride, gallic acid, and 3-[dimethyl-[2-(2-methylprop-2-enoyloxy) ethyl] azaniumyl] propane-1-sulfonate by free radical polymerization and a carbodiimide coupling reaction. The copolymer was further modified on the surface of poly(vinyl chloride) (PVC) samples using a simple dip-coating method and was characterized by different evaluations including Fourier transform infrared spectroscopy, the water contact angle, X-ray photoelectron spectroscopy, optical interferometry, and atomic force microscopy. Additionally, the results of a series of tribological tests at the microscopic level demonstrated that the friction coefficient of the copolymer-coated PVC samples was significantly reduced compared to that of the bare PVC samples. Furthermore, the pull out test at the macroscopic level was performed using copolymer-coated PVC catheters on a poly(dimethylsiloxane)-based test rig, and the result showed that the copolymer-coated PVC catheters were endowed with a greatly decreased and much more stable pull out force compared with that of the bare PVC catheters. In conclusion, the bioinspired self-adhesive lubricated coating developed herein may be applied as a universal and versatile method to enhance the lubrication performance of implanted biomedical devices.

A universal biocompatible coating for enhanced lubrication and bacterial inhibition.

Antibacterial coatings that inhibit bacterial adhesion are essential for many implanted medical devices. A variety of antibacterial strategies, such as repelling or killing bacteria, have been developed, but not yet been completely successful. Here, we develop a universal biocompatible coating for enhanced lubrication and bacterial inhibition. The coating is designed based on mussel-inspired surface-attachable dopamine bases and consists of lubricating zwitterionic polymers poly(2-methacryloxyethyl phosphorylcholine) (MPC) and a bacterial membrane destroying anti-bacteria molecule poly(3-hydroxybutyric acid) (PHB). The coating boasts strong adhesion to surfaces of various materials (such as polydimethylsiloxane (PDMS)/ceramic/316L stainless steel (316L SS); it is biocompatible, and cell/platelet/bacteria repelling, significantly inhibiting bacterial growth. We envision that our strategy represents a universal strategy for surface functionalization of a variety of biomedical devices and implants.

Self-Assembled Nanospheres with Enhanced Interfacial Lubrication for the Treatment of Osteoarthritis.

Osteoarthritis is associated with an increase in mechanical friction of the joint, which causes irreversible damage to articular cartilage. Consequently, it is crucial to restore joint lubrication for effectively treating osteoarthritis. In the present study, hyaluronic acid (HA)-based zwitterionic nanospheres with phosphocholine groups on the surface were synthesized, which achieved excellent lubrication behavior due to the hydration lubrication mechanism. Specifically, HA was initially thiolated and modified with hexadecylamine based on an amidation reaction, then it was grafted with 2-methacryloyloxyethyl phosphocholine (MPC) by the thiol-ene click reaction, and finally self-assembled into nanospheres (HA-MPC) by hydrophobic interaction and cross-linking of the thiol group. The lubrication test demonstrated that the HA-MPC nanospheres improved lubrication under shear force, with a 40% reduction in the friction coefficient compared with HA. The in vitro experiment indicated that the HA-MPC nanospheres had excellent biocompatibility, and they upregulated the cartilage anabolic gene and downregulated cartilage catabolic proteases as well as the pain-related gene. The in vivo test showed that the injection of HA-MPC nanospheres to the joint cavity could inhibit the development of osteoarthritis, which was examined based on histological staining and also morphological evaluation. In conclusion, the new self-assembled zwitterionic HA-MPC nanospheres may be intra-articularly injected for the effective treatment of osteoarthritis by restoring joint lubrication.

Polymeric coating lubricates nanocontainers to escape macrophage uptake for bioreceptor recognition.

Accurate drug delivery to the lesion has been deliberated for several decades, but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine. Although injection would reduce first-pass effect, macrophages in the blood can still recognize and phagocytose nanomedicine. Here we show that a lubricated nanocontainer, which is prepared based on polyelectrolytes and mesoporous silica nanoparticles, can accurately target muscarinic bioreceptor while escaping from the identification of macrophages. Through in vitro and in vivo studies, this nanocontainer, combining both immune escape and bioreceptor targeting, has greatly improved the drug bioavailability. Additionally, this nanocontainer shows good biocompatibility, and the targeted heart tissues and other important metabolic organs, such as liver and kidney, keep physiological structures and functions without the detection of side effects. Furthermore, the mechanism of immune escape for the developed nanocontainer has been investigated by lubrication test and molecular simulation. We anticipate that our study will establish a new perspective on the achievement of immune escape-based targeted drug delivery, which can provide a fundamental approach for the design of related biomaterials.

Perspectives on Ligand Properties of N-Heterocyclic Carbenes in Iron Porphyrin Complexes.

There has been considerable research interest in the ligand nature of N-heterocyclic carbenes (NHCs). In this work, two six-coordinate NHC iron porphyrin complexes [FeII(TTP)(1,3-Me2Imd)2] (TTP = tetratolylporphyrin, 1,3-Me2Imd = 1,3-dimethylimidazol-2-ylidene) and [FeIII(TDCPP)(1,3-Me2Imd)2]ClO4 (TDCPP = 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin) are reported. Single-crystal X-ray characterizations demonstrate that both complexes have strongly ruffled conformations and relatively perpendicular ligand orientations which are forced by the sterically bulky 1,3-Me2Imd NHC ligands. Multitemperature (4.2-300 K) and high magnetic field (0-9 T) Mössbauer and low-temperature (4.0 K) EPR spectroscopies definitely confirmed the low-spin states of [FeII(TTP)(1,3-Me2Imd)2] (S = 0) and [FeIII(TDCPP)(1,3-Me2Imd)2]ClO4 (S = 1/2). The similarity of 1,3-Me2Imd and imidazole, as well as the well-established correlations between the ligand nature and spectroscopic characteristics of [FeII,III(Porph)(L)2]0,+ (Porph: porphyrin; L: planar base ligand) species, allowed direct comparisons between the pair of ligands which revealed for the first time that NHC has a stronger π-acceptor ability than imidazoles, in addition to its very strong σ-donation.

Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis.

The occurrence of osteoarthritis (OA) is highly associated with the reduced lubrication property of the joint, where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism. In this study, bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel, we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment. Particularly, the lubricating microspheres (GelMA@DMA-MPC) were fabricated by dip coating a self-adhesive polymer (DMA-MPC, synthesized by free radical copolymerization) on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres (GelMA, prepared via microfluidic technology), and encapsulated with an anti-inflammatory drug of diclofenac sodium (DS) to achieve the dual-functional performance. The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres. In addition, the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model, and the biological tests including qRT-PCR, immunofluorescence staining assay, X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA. In summary, the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release, therefore representing a facile and promising technique for the treatment of OA.

Light-responsive dual-functional biodegradable mesoporous silica nanoparticles with drug delivery and lubrication enhancement for the treatment of osteoarthritis.

Visible light-responsive dual-functional biodegradable mesoporous silica nanoparticles with drug delivery and lubrication enhancement were constructed by supramolecular interaction between azobenzene-modified mesoporous silica nanoparticles (bMSNs-AZO) and ß-cyclodextrin-modified poly(2-methacryloyloxyethyl phosphorylcholine) (CD-PMPC). Visible light could effectively trigger azobenzene isomerization and thus induce drug release after passing through the dermal tissue. Additionally, the hydration layer formed by CD-PMPC on the surface of the nanoparticles played an important role in lubrication enhancement, which was beneficial for the treatment of osteoarthritis.

Self-adhesive lubricated coating for enhanced bacterial resistance.

Limited surface lubrication and bacterial biofilm formation pose great challenges to biomedical implants. Although hydrophilic lubricated coatings and bacterial resistance coatings have been reported, the harsh and tedious synthesis greatly compromises their application, and more importantly, the bacterial resistance property has seldom been investigated in combination with the lubrication property. In this study, bioinspired by the performances of mussel and articular cartilage, we successfully synthesized self-adhesive lubricated coating and simultaneously achieved optimal lubrication and bacterial resistance properties. Additionally, we reported the mechanism of bacterial resistance on the nanoscale by studying the adhesion interactions between biomimetic coating and hydrophilic/hydrophobic tip or living bacteria via atomic force microscopy. In summary, the self-adhesive lubricated coating can effectively enhance lubrication and bacterial resistance performances based on hydration lubrication and hydration repulsion, and represent a universal and facial strategy for surface functionalization of biomedical implants.

Dopamine/Phosphorylcholine Copolymer as an Efficient Joint Lubricant and ROS Scavenger for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease and its progression and pathogenesis are highly associated with the significant increase of joint friction and overproduction of reactive oxygen species (ROS) in inflammation. Combination of ROS elimination and lubrication enhancement may provide a novel strategy for the treatment of OA. In the present study, a pure biomaterial and nondrug system P(DMA-co-MPC), synthesized via free radical copolymerization, was designed and developed for the first time using 2-methacryloxyethyl phosphorylcholine (MPC) as a bioinspired lubricant and N-(3,4-dihydroxyphenethyl)methacrylamide (DMA) as an ROS scavenger. Our results showed that the P(DMA-co-MPC) aggregates could efficiently eliminate the ROS radicals and provide good lubrication property by adjusting the molar ratio of DMA and MPC in the copolymer. It is attributed to the antioxidant function of the hydroquinone moiety in DMA and the hydration lubrication effect of the zwitterionic phosphocholine group in MPC. Furthermore, the in vitro experiments demonstrated that the P(DMA-co-MPC) showed good biocompatibility with MC3T3-E1 cells and intracellular anti-inflammatory property by inhibiting the production of ROS and regulating the expression levels of pro-inflammatory cytokines, pain-related gene, anabolic genes, and catabolic genes. In conclusion, the drug-free P(DMA-co-MPC) aggregates developed herein can achieve dual functions of lubrication enhancement and anti-inflammatory effect and thus they may be representative as promising candidates for the treatment of OA.

Synthesis, crystal structure and characterizations of di-µ-cyanido-1:2κ2 N:C;2:3κ2 C:N-bis-(4,7,13,16,21,24-hexa-oxa-1,10-di-aza-bicyclo-[8.8.8]hexacosa-ne)-1κ8 N 1,N 10,O 4,O 7,O 13,O 16,O 21,O 24;3κ8 N 1,N 10,O 4,O 7,O 13,O 16,O 21,O 24-[5,10,15,20-tetra-kis-(4-chloro-phen-yl)porphyrinato-2κ4 N]-2-iron(II)-1,3-dipotassium(I) tetra-hydro-furan disolvate with an unknown solvent.

The title compound, [Fe(C44H24N8Cl4)(CN)2][K2(C18H36N2O6)2]·2C4H8O was synthesized and characterized by single-crystal X-ray diffraction as well as FTIR and UV-vis spectroscopy. The central FeII ion is coordinated by four pyrrole N atoms of the porphyrin core and two C atoms of the cyano groups in a slightly distorted octa-hedral coordination environment. The complex mol-ecule crystallizes with two tetra-hydro-furan solvent mol-ecules, one of which was refined as disordered over two sets of sites with refined occupancies of 0.619 (5) and 0.381 (5). It has a distorted porphyrin core with mean absolute core-atom displacements Ca, Cb, Cm and Cav of 0.32 (3), 0.22 (3), 0.56 (2) and 0.37 (14) Å, respectively. The axial Fe-Ccyano bond lengths are 1.991 (2) and 1.988 (2) Å. The average Fe-Np (Np is a porphyrin N atom) bond length is 1.964 (10) Å. One of the O atoms and several C atoms of the 222 moiety [222 = 4,7,13,16,21,24-hexa-oxa-1,10-di-aza-bicyclo-[8.8.8]hexa-cosa-ne] were refined as disordered over two sets of sites with occupancy ratios of 0.739 (6):0.261 (6) and 0.832 (4):0.168 (4). Additional solvent mol-ecules were found to be highly disordered and their contribution to the scattering was removed using the SQUEEZE procedure in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9-18], which indicated a solvent cavity of volume 372 Å3 containing approximately 83 electrons. These solvent mol-ecules are not considered in the given chemical formula and other crystal data.

New Insights into the Ligand Nature of Carbene: Synthesis and Characterizations of Six-Coordinate Iron(II) Carbene Porphyrin Complexes.

Several six-coordinate iron(II) carbene tetra(pentafluorophenyl)porphyrin (TFPP) complexes, [Fe(TFPP)(CPh2)(1-EtIm)] (1-EtIm = 1-ethylimidazole) and [Fe(TFPP)(CPh2)(1,2-Me2Im)] (1,2-Me2Im = 1,2-dimethylimidazole), are isolated and studied by UV-vis, single-crystal X-ray, and Mössbauer spectroscopies. The single-crystal structural studies revealed noteworthy features including strong and "hard" axial carbene bonds (Fe-C) but "flexible" trans ligand bonds (Fe-NIm). The Mössbauer spectra of [Fe(TFPP)(CPh2)(1-EtIm)] and [Fe(TFPP)(CPh2)(1,2-Me2Im)] are obtained on solid-state samples between 25 and 295 K, which give very large Δ EQ values (1.8-1.9 mm/s), suggesting a weak effect of the trans imidazole ligands. Comparisons with diatomic carbon-donor ligands (CO, CS, and CN-) demonstrate considerably stronger π bonding of the :CPh2 carbene.