Wilhelmsenconnell3869

With the outstanding synergistic sterilizing effect and excellent biocompatibility, the VAT hydrogel would be a promising candidate for bacteria-associated wound infections.Fast-gelling chitosan thermosensitive hydrogels have proven to be excellent matrices for targeted drug-delivery and cell therapy. In this work, we demonstrate the possibility of designing injectable bioadhesive hydrogels with a high gelation rate by modifying chitosan with catechol (cat-CH) and using sodium bicarbonate (SHC) as a gelling agent. Cat-CH/SHC hydrogels gel under 5 min at 37 °C and reach a high secant modulus after 24 h (E = 90 kPa at 50% strain). Besides, they show significantly higher adhesion to tissues than chitosan hydrogels thanks to the combination of catechol grafting and physical crosslinking. Their pH and osmolality stayed inside the physiological range. While biocompability tests will be mandatory to conclude regarding their potential for drug or cell encapsulation, these hydrogels uniquely combine physiological compatibility, injectability, fast gelation, good cohesion, and bioadhesion.Bone transplant is still the gold standard approach when dealing with orthopedic trauma or disease. When this solution is not possible, scaffolding is a possibility provided by bone tissue engineering. To support the regeneration process, damaged bone tissue is removed and replaced by porous scaffold structures. In recent years, additive manufacturing has shown huge potential to produce scaffold structures with the required performance. In the current work, PLA scaffolds with different designs were 3D printed, using optimal manufacturing parameters. Scaffolds with three different porosity values were obtained by changing the filament offset from 571 to 1333 μm. A total of twelve designs were tested under monotonic and dynamic compression conditions. Numerical analysis showed good correlation with experimental results, allowing for a better assessment of scaffold mechanical behavior. Stress relaxation was measured on four different strain levels, assessing scaffold's behavior after implantation and consequent static response over time. Overall, orthogonal design provided better performance, due to improved material deposition. With lower porosity scaffolds equilibrium stress reached 24 MPa after 300 s relaxation time under 4% deformation, and the obtained equilibrium modulus was 428 MPa. Overall, attained results show that 3D printing with PLA can be applied in the manufacture of scaffolds for trabecular bone replacement.A novel nanodrug delivery system (NDDS) based on block copolymers of Poly(DEA)-block-Poly(PgMA) (PDPP) was developed to enhance in vitro cellular uptake and anticancer efficacy. pH-responsive doxorubicin (DOX) based small molecule prodrug (DOX-hyd-N3) and mPEG-N3 were co-conjugated onto PDPP via copper-catalyzed "Click chemistry" to give a dual pH-responsive polymeric prodrug (mPEG-g-PDPP-g-hyd-DOX), which could be self-assembled into core-shell polymeric micelles (M(DOX)) with particles size of 81 ± 1 nm in aqueous phase. Additionally, the pH-responsive charge-reversal, stability and drug release behaviour at different pHs were then evaluated. Moreover, the surface charge of M(DOX) could quickly convert from negative (-6.64 ± 3.37 mV) to positive (5.35 ± 1.33 mV) thanks to the protonation of Poly(DEA) moieties as the pH value decreased from 7.4 during blood circulation to 6.5 in extracellular of tumour tissues. Meanwhile, according to the cytotoxicity determined by CCK-8 assay, cellular uptake, flow-cytometric and apoptosis profiles of two human cancer cell lines (HeLa and SW480), we could draw the conclusion that the cellular uptake and anticancer efficacy were significantly enhanced when cells were incubated with micelles at pH 6.5 due to the charge-reversal of micelles from negative to positive. With the protonation of Poly(DEA) moieties in acidic extracellular microenvironment and the pH-responsive DOX release with hydrazone linkage in endo/lysosome pH, this dual pH-responsive-charge-reversal micelle platform might become an encouraging strategy for more effective cancer treatment.Nanocarriers have demonstrated great promise in the delivery of hydrophobic drugs particularly to tumor spaces by enhanced permeability and retention (EPR) effects. Mesoporous silica nanoparticles (MSNs) are the attractive nanocarrier system to reduce the drug's toxic side effects, enable controlled drug release, prevent drug degradation and provide a biocompatible and biodegradable high surface area carrier. Surface-modified MSNs have been applied to increase drug loading and efficiency. In this study, functionalized MSNs loaded with methotrexate (MTX) were designed for use as a cytotoxic agent. The MSNs were first modified with 3-triethoxysilylpropylamine (APTES) and then with chitosan through covalent coupling mediated by glutaraldehyde. The physicochemical properties of the nanoparticles were optimized for each step. Selleck STA-9090 The loading percentage (12.2%) and release profile of MTX as an anti-breast cancer drug, loaded at amine-modified MSNs, were measured via high performance liquid chromatography (HPLC). Moreover, the uptake profiles of fluorescein isothiocyanate (FITC)-labeled MSN-APTES-chitosan with or without MTX were monitored on MCF7 cancer cells via confocal microscopy. Following exposure of nanoparticles to body fluids, they were surrounded by specific proteins that may affect their cellular uptake. Hence, the adsorption profiles of protein corona on the surface of MSN, amine-modified MSN and MTX-loaded MSN-APTES-chitosan were analyzed. The cytotoxic potential for killing breast cancer cells was also studied. The MTX loaded MSN-APTES-chitosan showed a positive effect at a low dose (0.5 μM MTX). In this study, we introduce a new method to synthesize biodegradable MSNs with small and uniform particle size, achieve high MTX loading via covalent amine and chitosan-functionalization, monitor the cellular uptake and demonstrate the potential to decrease the viability of breast cancer cells at low dose.Synthetic polymers are widely employed for bone tissue engineering due to their tunable physical properties and biocompatibility. Inherently, most of these polymers display poor antimicrobial properties. Infection at the site of implantation is a major cause for failure or delay in bone healing process and the development of antimicrobial polymers is highly desired. In this study, silver nanoparticles (AgNps) were synthesized in polycaprolactone (PCL) solution by in-situ reduction and further extruded into PCL/AgNps filaments. Customized 3D structures were fabricated using the PCL/AgNps filaments through 3D printing technique. As demonstrated by scanning electron microscopy, the 3D printed scaffolds exhibited interconnected porous structures. Furthermore, X-ray photoelectron spectroscopy analysis revealed the reduction of silver ions. Transmission electron microscopy along with energy-dispersive X-ray spectroscopy analysis confirmed the formation of silver nanoparticles throughout the PCL matrix. In vitro enzymatic degradation studies showed that the PCL/AgNps scaffolds displayed 80% degradation in 20 days.