Sequence-Reversible Construction of Oxygen-Rich Block Copolymers from Epoxide Mixtures by Organoboron Catalysts.

Switchable catalysis, in combination with epoxide-involved ring-opening (co)polymerization, is a powerful technique that can be used to synthesize various oxygen-rich block copolymers. Despite intense research in this field, the sequence-controlled polymerization from epoxide congeners has never been realized due to their similar ring-strain which exerts a decisive influence on the reaction process. Recently, quaternary ammonium (or phosphonium)-containing bifunctional organoboron catalysts have been developed by our group, showing high efficiency for various epoxide conversions. Herein, we, for the first time, report an operationally simple pathway to access well-defined polyether-block-polycarbonate copolymers from mixtures of epoxides by switchable catalysis, which was enabled through thermodynamically and kinetically preferential ring-opening of terminal epoxides or internal epoxides under different atmospheres (CO2 or N2) using one representative bifunctional organoboron catalyst. This strategy shows a broad substrate scope as it is suitable for various combinations of terminal epoxides and internal epoxides, delivering corresponding well-defined block copolymers. NMR, MALDI-TOF, and gel permeation chromatography analyses confirmed the successful construction of polyether-block-polycarbonate copolymers. Kinetic studies and density functional theory calculations elucidate the reversible selectivity between different epoxides in the presence/absence of CO2. Moreover, by replacing comonomer CO2 with cyclic anhydride, the well-defined polyether-block-polyester copolymers can also be synthesized. This work provides a rare example of sequence-controlled polymerization from epoxide mixtures, broadening the arsenal of switchable catalysis that can produce oxygen-rich polymers in a controlled manner.

Enhancing the antibacterial activity of biomimetic HA coatings by incorporation of norvancomycin.

BACKGROUND: Bacterial infections associated with the use of biomaterials remain a great challenge for orthopedic surgery. The main purpose of the work discussed in this paper was to improve the antibacterial activity of a biomimetic calcium phosphate (CP) coating widely used in orthopedic biomaterials by incorporation of norvancomycin in the biomimetic process. METHODS: CP coating and CP coating containing norvancomycin were produced on a titanium alloy (Ti6Al4V) surface by a biomimetic process. The morphology, surface crystal structure, and concentrations of elements in the coatings were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDX), respectively. The amount of norvancomycin and its release were investigated by UV-visible spectroscopy. MTT was used to investigate cell behavior. The morphology of adhered bacteria was observed by SEM. Antibacterial activity was expressed as inhibition zone by using Staphylococcus aureus (ATCC 25923) as model bacteria. RESULTS: Results from SEM, EDX, and XRD revealed formation of a hydroxyapatite (HA) coating. The amount of antibiotic in the CP coating increased with increasing concentration of norvancomycin in the coating solution, followed by a plateau when the concentration of norvancomycin in the coating solution reached 600 mg/l. Approximately 2.16 µg norvancomycin per mg coating was co-precipitated with the CP layer onto titanium alloy discs when 600 mg/l norvancomycin coating solution was applied. The norvancomycin had a fast release profile followed by slow release. The MTT test of osteoblast cell cultures suggested that coatings containing norvancomycin did not cause any cytotoxicity compared with the CP coating and control titanium plate. The antibacterial activity test showed that the norvancomycin released from the coatings inhibited the growth of Staphylococcus aureus; more bacteria were found on the CP coating than on the norvancomycin-loaded coating. CONCLUSIONS: A norvancomycin-loaded HA-like coating was successfully obtained on titanium surfaces. The norvancomycin incorporated had no negative effects on osteoblast cell behavior. The released norvancomycin results in excellent antibacterial activity of Ca-P coatings. Therefore, incorporation of norvancomycin can enhance antibacterial activity and the norvancomycin-loaded CP coating can be used to inhibit post-surgical infections in orthopaedics.

Chondroitin sulfate-enriched hierarchical multichannel polydopamine nanoparticles with ultrahigh sorption capacity for separation of low-density lipoprotein.

A hierarchical multichannel polydopamine (HMPDA) nanoparticle with ample chondroitin sulfate (CS) is fabricated via modification of the silane coupling agent (APTES), followed by grafting CS on the unique bicontinuous open channels of HMPDA through amidation reaction. The obtained nanoparticles with both mesopores and macropores, abbreviated as HMPDA-A-CS15, possess a total pore volume of 0.3398 cm3 g-1, and a large surface area up to 69.10 m2 g-1. The as-prepared HMPDA-A-CS15 exhibits significantly enhanced selectivity for the separation of LDL, which is attributed to the specific recognition effect of CS for LDL. Furthermore, the unique large open channels endow the HMPDA-A-CS15 nanoparticles with a gratifying sorption capacity (1015.2 mg g-1) for LDL adsorption. The captured LDL can be stripped using 0.5% (v/v) ammonia solution with the advantage of easy atomization in downstream mass spectrometry (MS) analyses, and a recovery of 71.7% is achieved. Moreover, HMPDA-A-CS15 is further employed in the enrichment of LDL, which can be separated from the complex serum of simulated hypercholesterolemia patients with a favorable adsorption performance, as illustrated by the SDS-PAGE technique.

A Salt Stimulus-Responsive Nanohydrogel for Controlled Fishing Low-Density Lipoprotein with Superior Adsorption Capacity.

A salt-responsive nanoplatform is constructed through a simple tactic by tethering zwitterionic nanohydrogels (NGs) on a carboxylated silica (SiO2-COOH) framework. Chondroitin sulfate (CS), with a specific recognition effect for low-density lipoprotein (LDL), is modified to NGs by amidation reaction. Water retention and swelling properties of NGs are greatly enhanced in a saline environment attributed to the anti-polyelectrolyte effect. It endows the SiO2-NGs-CS framework a sensitive salt-responsive property, and thus, more CS moieties are exposed. The controlled adsorption of LDL with an adsorption efficiency of 7.2 to 93% is achieved by adjusting the concentration of MgCl2 from 0 to 0.1 mol L-1. SiO2-NGs-CS exhibits excellent adsorption capacity for fishing LDL, acquiring the highest adsorption capacity of 898.1 mg g-1. Moreover, SiO2-NGs-CS shows superior selectivity to the other three proteins with similar isoelectric points (pIs) to LDL. The captured LDL is readily stripped by 0.2% (m/m) SDS with a recovery of 95.4%. The superior separation performance of SiO2-NGs-CS is demonstrated by the isolation and selective discrimination of LDL from the simulated serum of hypercholesterolemia patients, as illustrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis assays.

Tolerance induced by Porphyromonas gingivalis may occur independently of TLR2 and TLR4.

OBJECTIVE: Periodontitis is a microbe-induced chronic inflammatory disease. Previous exposure of the host to bacteria or their virulence factors leads to refractory responses to further stimuli, which is called tolerance. Porphyromonas gingivalis (P. gingivalis) is one of the most important pathogenic microorganisms associated with periodontitis, and is a potent inducer of pro- and anti-inflammatory cytokines. The aim of this study was to explore the roles and possible mechanisms of tolerance induced by P. gingivalis. METHODS: THP-1-derived macrophages were pretreated with 1x108 colony-forming units/ml P. gingivalis ATCC 33277 or 21 clinical isolates from moderate to severe chronic periodontitis patients (24 h), washed (2 h) and treated with P. gingivalis ATCC 33277 or the same clinical isolates again (24 h). Levels of pro-inflammatory cytokines TNF-α and IL-1ß and anti-inflammatory cytokine IL-10 in supernatants were detected by ELISA. Moreover, to identify the possible mechanisms for the changes in cytokine secretion, Toll-like receptor 2 (TLR2) and TLR4 protein expressions were explored in these cells by flow cytometry. RESULTS: After repeated challenge with P. gingivalis ATCC 33277 or clinical isolates, production of TNF-α and IL-1ß in macrophages was decreased significantly compared with that following a single stimulation (p<0.05), while only comparable levels of IL-10 were detected in P. gingivalis ATCC 33277 or clinical isolate-tolerized cells (p>0.05). In addition, there was interstrain variability in the ability to induce IL-1ß and IL-10 production after repeated P. gingivalis stimulation. However, no significant changes in TLR2 or TLR4 were detected in macrophages that were repeatedly treated with P. gingivalis ATCC 33277 or clinical isolates compared with those stimulated with P. gingivalis only once (p>0.05). CONCLUSIONS: Repeated P. gingivalis stimulation triggered tolerance, which might contribute to limiting periodontal inflammation. However, tolerance induced by P. gingivalis might develop independently of TLR2 and TLR4 and be related to molecules in signaling pathways downstream of TLR2 and TLR4.