Polymeric Nanocarriers with Controlled Chain Flexibility Boost mRNA Delivery In Vivo through Enhanced Structural Fastening.

Messenger RNA (mRNA) shows high therapeutic potential, though effective delivery systems are still needed for boosting its application. Nanocarriers loading mRNA via polyion complexation with block catiomers into core-shell micellar structures are promising systems for enhancing mRNA delivery. Engineering the interaction between mRNA and catiomers through polymer design can promote the development of mRNA-loaded micelles (mRNA/m) with increased delivery efficiency. Particularly, the polycation chain rigidity may critically affect the mRNA-catiomer interplay to yield potent nanocarriers, yet its effect remains unknown. Herein, the influence of polycation stiffness on the performance of mRNA/m by developing block complementary catiomers having polycation segments with different flexibility, that is, poly(ethylene glycol)-poly(glycidylbutylamine) (PEG-PGBA) and PEG-poly(L-lysine) (PEG-PLL) is studied. PEG-PGBA allows more than 50-fold stronger binding to mRNA than the relatively more rigid PEG-PLL, resulting in mRNA/m with enhanced protection against enzymatic attack and polyanions. mRNA/m from PEG-PGBA significantly enhances mRNA in vivo bioavailability and increased protein translation, indicating the importance of controlling polycation flexibility for forming stable polyion complexes with mRNA toward improved delivery.

In situ surface modification on dental composite resin using 2-methacryloyloxyethyl phosphorylcholine polymer for controlling plaque formation.

Composite resins (CRs) are widely used as dental restorative materials for caries treatment. They cause problems of secondary caries since Streptococcus mutans stays in the dental plaque, which the surface exists and produces acidic compounds during metabolism. The dental plaque depositions are induced by the protein adsorption on the surface. Therefore, suppression of protein adsorption on the surface of the CRs is important for inhibiting the formation of plaque and secondary caries. In this study we developed a surface treatment to provide an antibiofouling nature to the CRs by chemical reaction with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers in the oral cavity during dental treatment. To carry out the photochemical reaction on the remaining polymerizable groups of CRs, we synthesized the MPC polymer with a polymerizable group in the side chain. The MPC polymer could bind on the surfaces of the CRs chemically under dental treatment procedures. The treated surface showed significant resistance to oral protein adsorption and bacterial adhesion even when the surface was brushed with a toothbrush. Thus, we concluded that the photochemical reaction of the MPC polymer with the CRs in the oral cavity was good for making an antibiofouling surface and preventing secondary caries.

Reducing fretting-initiated crevice corrosion in hip simulator tests using a zirconia-toughened alumina femoral head.

Taper fretting corrosion is considered a potentially limiting factor for total hip arthroplasty longevity. Recently, attention has been focused on new materials for ceramic femoral heads, for example, zirconia-toughened alumina (ZTA), since they have an alternative bearing surface that can improve the wear resistance. Moreover, ceramics have high chemical stability and corrosion resistance. In this study, we evaluated the effects of ZTA and Co-Cr-Mo alloy femoral heads on their taper fretting and/or corrosion characteristics under a controlled hip simulator test. After the test, less fretting and corrosion were observed in the taper surface of the trunnion against the ZTA femoral head than for that against the Co-Cr-Mo alloy femoral head. In addition, corrosion damages were only observed in the lateral-distal taper surface (noncontact area) of the trunnion in the Co-Cr-Mo alloy femoral head group. The ZTA femoral head group also eliminated the potential for Co ion release into the lubricants from taper corrosion, reducing the possibility of adverse local tissue inflammatory responses. In conclusion, ZTA femoral heads showed markedly less fretting corrosion compared to Co-Cr-Mo alloy femoral heads and have a lower potential for metal ion release. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2815-2826, 2018.

Wear resistance of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted carbon fiber reinforced poly(ether ether ketone) liners against metal and ceramic femoral heads.

Younger, active patients who undergo total hip arthroplasty (THA) have increasing needs for wider range of motion and improved stability of the joint. Therefore, bearing materials having not only higher wear resistance but also mechanical strength are required. Carbon fiber-reinforced poly(ether ether ketone) (CFR-PEEK) is known as a super engineering plastic that has great mechanical strength. In this study, we focused on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted CFR-PEEK and investigated the effects of PMPC grafting and the femoral heads materials on the wear properties of CFR-PEEK liners. Compared with untreated CFR-PEEK, the PMPC-grafted CFR-PEEK surface revealed higher wettability and lower friction properties under aqueous circumstances. In the hip simulator wear test, wear particles generated from the PMPC-grafted CFR-PEEK liners were fewer than those of the untreated CFR-PEEK liners. There were no significant differences in the size and the morphology of the wear particles between the differences of PMPC-grafting and the counter femoral heads. Zirconia-toughened alumina (ZTA) femoral heads had significantly smoother surfaces compared to cobalt-chromium-molybdenum alloy femoral heads after the hip simulator test. Thus, we conclude that the bearing combination of the PMPC-grafted CFR-PEEK liner and ZTA head is expected to be a lifelong bearing interface in THA. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1028-1037, 2018.

A hydrated phospholipid polymer-grafted layer prevents lipid-related oxidative degradation of cross-linked polyethylene.

The surface and substrate of a cross-linked polyethylene (CLPE) liner are designed to achieve resistance against oxidative degradation in the construction of hip joint replacements. In this study, we aimed to evaluate the oxidative degradation caused by lipid absorption of a highly hydrophilic nanometer-scaled thickness layer prepared by grafting a poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer and a high-dose gamma-ray irradiated CLPE with vitamin E blending (HD-CLPE[VE]). The HD-CLPE(VE) and PMPC-grafted HD-CLPE(VE) exhibited extremely high oxidation resistance regardless of lipid absorption, even though residual-free radical levels were detectable. The water wettability of the PMPC-grafted CLPE and PMPC-grafted HD-CLPE(VE) surfaces was considerably greater than that of untreated surfaces. The hydrated PMPC-grafted layer also exhibited extremely low solubility for squalene. Lipids such as squalene and cholesterol esters diminished the oxidation resistance of CLPE despite the vitamin E improvement. Notably, the PMPC-grafted surface was resistant to lipid absorption and diffusion as well as subsequent lipid-related oxidative degradation, likely because of the presence of the hydrated PMPC-grafted layer. Together, these results provide preliminary evidence that the resistance against lipid absorption and diffusion of a hydrated PMPC-grafted layer might positively affect the extent of resistance to the in vivo oxidation of orthopedic implants.

Fabrication of a live cell-containing multilayered polymer hydrogel membrane with micrometer-scale thickness to evaluate pharmaceutical activity.

We propose a spinning-assisted layer-by-layer method for simple fabrication of a multilayered polymer hydrogel membrane that contains living cells. Hydrogel formation occurred based on the spontaneous cross-linking reaction between two polymers in aqueous solution. A water-soluble 2-methacryloyloxyethyl phosphorylcholine polymer bearing phenylboronic acid groups (PMBV) and poly(vinyl alcohol) (PVA) were used as polymers for hydrogel membrane formation. Changing the number of hydrogel membrane layers, polymer concentration, spinning rate, and processing time for diffusion-dependent gelation of PMBV and PVA facilitated the regulation of the multilayered polymer hydrogel membrane thickness and morphology. We concluded that a multilayered polymer hydrogel membrane prepared using 5.0 wt% PMBV and 5.0 wt% PVA at a spinning rate of 2000 rpm was suitable for precise spatial control of cells in single layers. This multilayered polymer hydrogel membrane was used to prepare a single cell-laden layer to minimize barriers to the diffusion of bioactive compounds while preserving the three-dimensional (3-D) context. The pharmaceutical effects of one of the anticancer agents, paclitaxel, on a human cervical cancer line, HeLa cells, were evaluated in vitro, and the usability of this culture model was demonstrated.

Poly(2-methacryloyloxyethyl phosphorylcholine) grafting and vitamin E blending for high wear resistance and oxidative stability of orthopedic bearings.

The ultimate goal in manipulating the surface and substrate of a cross-linked polyethylene (CLPE) liner is to obtain not only high wear resistance but also high oxidative stability and high-mechanical properties for life-long orthopedic bearings. We have demonstrated the fabrication of highly hydrophilic and lubricious poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) grafting layer onto the antioxidant vitamin E-blended CLPE (HD-CLPE(VE)) surface. The PMPC grafting layer with a thickness of 100 nm was successfully fabricated on the vitamin E-blended CLPE surface by using photoinduced-radical graft polymerization. Since PMPC has a highly hydrophilic nature, the water wettability and lubricity of the PMPC-grafted CLPE and HD-CLPE(VE) surfaces were greater than that of the untreated CLPE surface. The PMPC grafting contributed significantly to wear reduction in a hip-joint simulator wear test. Despite high-dose gamma-ray irradiation for cross-linking and further UV irradiation for PMPC grafting, the substrate modified by vitamin E blending maintained high-oxidative stability because vitamin E is an extremely efficient radical scavenger. Furthermore, the mechanical properties of the substrate remained almost unchanged even after PMPC grafting or vitamin E blending, or both PMPC grafting and vitamin E blending. In conclusion, the PMPC-grafted HD-CLPE(VE) provided simultaneously high-wear resistance, oxidative stability, and mechanical properties.

Reduced platelets and bacteria adhesion on poly(ether ether ketone) by photoinduced and self-initiated graft polymerization of 2-methacryloyloxyethyl phosphorylcholine.

Aromatic poly(ether ether ketone) (PEEK) is a super engineering plastic, which has good mechanical properties and is resistant to physical and chemical stimuli. We have, therefore, attempted to use PEEK in cardiovascular devices. Synthetic cardiovascular devices require both high hemocompatibility and anti-inflammatory activity in addition to the mechanical properties. We modified the PEEK surface by photoinduced and self-initiated graft polymerization with 2-methacryloyloxyethyl phosphorylcholine (MPC; PMPC-grafted PEEK) for obtaining good antithrombogenicity. Polymerization was carried out on the surface of PEEK under radiation of ultraviolet (UV) light during which we controlled monomer concentrations, temperatures, and UV intensities. The biological performance of the PMPC-grafted PEEK was examined and compared with that of unmodified PEEK. With increase in the thickness of the PMPC layer, the amount of fibrinogen adsorption decreased significantly in comparison to that in the case of unmodified PEEK. When placed in contact with human platelet-rich plasma, surface of the PMPC-grafted PEEK clearly showed inhibition of platelet adhesion and activation. Also, bacterial adhesion was reduced dramatically on the PMPC-grafted PEEK. Thus, the PMPC grafting on PEEK improved the antithrombogenicity.

Effects of tea catechins on the gastrointestinal mucosa in rats.

Although tea catechins are known to exert a potent antiulcer effect on the alimentary tract, there is scant information concerning their effects on normal mucus cell functions. Using original anti-mucin monoclonal antibodies, we studied the influences of long-term administration of catechins on the quantity and quality of mucin in rat gastrointestinal mucosa. Administration of 0.5% tea catechins significantly increased the mucin content of the ileum, but not the stomach. An enzyme-linked immunosorbent assay (ELISA) showed no remarkable qualitative changes in gastric mucin, but a selective increase and decrease in sulfo- and sialomucins, respectively, in the ileum of rats administered catechins. The ELISA results were consistent with both the immunohistochemical findings and the high-iron diamine-alcian blue staining pattern. These findings indicate that tea catechins modulate ileal mucin metabolism in the ileal mucosa, suggesting that further studies focusing on the ileal epithelium will assist in further elucidation of the mechanism of catechin effects.

Effect of tea catechins on body fat accumulation in rats fed a normal diet.

Although it is known that tea catechins exert potent effects in obese subjects, there is scant information concerning these effects on body weight gain and body fat accumulation in the non-obese. We studied normal rats fed a normal diet and water containing either 0.1% or 0.5% tea catechins to examine the effects on body fat content and serum cholesterol levels, as well as evaluating whether the effect is related to bile acids, which in recent years have emerged as an inducer of energy expenditure. The administration of 0.5% catechins decreased the accumulation of body fat and the serum levels of cholesterol and bile acids. These results indicate that tea catechins modulate lipid metabolism not only in obese subjects, but also in the non-obese.