Multivalent dendrimers presenting spatially controlled clusters of binding epitopes in thermoresponsive hyaluronan hydrogels

The controlled presentation of biofunctionality is of key importance for hydrogel applications in cell-based regenerative medicine. Here, a versatile approach was demonstrated to present clustered binding epitopes in an injectable, thermoresponsive hydrogel. Well-defined multivalent dendrimers bearing four integrin binding sequences and an azido moiety were covalently grafted to propargylamine-derived hyaluronic acid (Hyal-pa) using copper-catalyzed alkyne-azide cycloaddition (CuAAC), and then combined with pN-modified hyaluronan (Hyal-pN). The dendrimers were prepared by synthesizing a bifunctional diethylenetriamine pentaacetic acid core with azido and NHBoc oligo(ethylene glycol) aminoethyl branches, then further conjugated with solid-phase synthesized RGDS and DGRS peptides. Azido terminated pN was synthesized by reversible addition-fragmentation chain transfer polymerization and reacted to Hyal-pa via CuAAC. Nuclear magnetic resonance (NMR), high performance liquid chromatography, size exclusion chromatography and mass spectroscopy proved that the dendrimers had well-defined size and were disubstituted. NMR and atomic absorption analysis confirmed the hyaluronan was affixed with dendrimers or pN. Rheological measurements demonstrated that dendrimers do not influence the elastic or viscous moduli of thermoresponsive hyaluronan compositions at a relevant biological concentration. Finally, human mesenchymal stromal cells were encapsulated in the biomaterial and cultured for 21days, demonstrating the faculty of this dendrimer-modified hydrogel as a molecular toolbox for tailoring the biofunctionality of thermoresponsive hyaluronan carriers for biomedical applications.The authors acknowledge the financial support from the AO Foundation (grant number C10-60S) and the consortium grant from AO Exploratory Research Board and Spanish Ministry of Economy and Competitiveness (SAF2011-30508-C02-01) and the Generalitat de Catalunya (2009SGR 1024). CIBER-BBN (DP) and La Caixa social program (PF) are also acknowledged for their financial support. The authors are grateful to Mr. Markus Glarner (AO Research Institute) and Mr. Matti Kesti (ETH Zurich) for their help with the polymer synthesis and rheology, respectively. The authors wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.Peer reviewe

Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease

AbstractTo identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy

Plasma Treatment of Polypropylene-Based Wood–Plastic Composites (WPC): Influences of Working Gas

In this study, a polypropylene (PP)-based wood–plastic composite with maleic anhydride-grafted polypropylene (MAPP) as a coupling agent and a wood content of 60% was extruded and specimens were injection molded. The samples were plasma treated utilizing a dielectric barrier discharge (DBD) setup with three different working gases: Ar/O2 (90%/10%), Ar/N2 (90%/10%), and synthetic air. This process aims to improve the coating and gluing properties of the otherwise challenging apolar surface of PP based wood–plastic composites (WPC). Chemical analysis with X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR) showed the formation of oxygen-based functional groups on the surface, independently from the working gas used for the treatment. Laser scanning microscopy (LSM) examined the surface roughness and revealed that the two argon-containing working gases roughened the surface more than synthetic air. However, the contact angle for water was reduced significantly after treatment, revealing measurement artifacts for water and diiodomethane due to the severe changes in surface morphology. The adhesion of acrylic dispersion coating was significantly increased, resulting in a pull-off strength of approximately 4 N/mm2, and cross-cut tests assigned the best adhesion class (0), on a scale from 0 to 5, after plasma treatment with any working gas

Surface Preparation and Treatment for Large-Scale 3D-Printed Composite Tooling Coating Adhesion

Recent advances in large-scale thermoplastic additive manufacturing (AM), using fused deposition modelling (FDM), have shown that the technology can effectively produce large aerospace tools with common feed stocks, costing 2.3 $/kg, such as a 20$/kg) than the filament feedstocks for desktop 3D printers (20⁻50 $/kg). Additionally, large-scale AM machines have a higher material throughput on the order of 50 kg/h. This enables the cost-efficient tool production for several industries. Large-scale 3D-printed tooling will be computerized numerical control (CNC)-machined and -coated, to provide a surface suitable for demolding the composite parts. This paper outlines research undertaken to review and improve the adhesion of the coating systems to large, low-cost AM composite tooling, for marine or infrastructure composite applications. Lower cost tooling systems typically have a lower dimensional accuracy and thermal operating requirements than might be required for aerospace tooling. As such, they can use lower cost commodity grade thermoplastics. The polymer systems explored in the study included polypropylene (PP), styrene-maleic anhydride (SMA), and polylactic acid (PLA). Bio-based filler materials were used to reduce cost and increase the strength and stiffness of the material. Fillers used in the study included wood flour, at 30% by weight and spray-dried cellulose nano-fibrils, at 20% by weight. Applicable adhesion of the coating was achieved with PP, after surface treatment, and untreated SMA and PLA showed desirable coating adhesion results. PLA wood-filled composites offered the best properties for the desired application and, furthermore, they have environment-friendly advantages

Surface Activation of Polylactic Acid-Based Wood-Plastic Composite by Atmospheric Pressure Plasma Treatment

Wood-plastic composite (WPC) based on a polylactic acid (PLA) matrix is a promising material since it is biobased, degradable, sustainable, and 3D printable. However, due to its coloring, visible layers after 3D-printing, and small build volumes of these printers, a coating or gluing of parts might be required. This study investigates the influence of a dielectric barrier discharge (DBD) plasma treatment of PLA-based WPC to activate the surface and improve, e.g., coating capabilities. X-ray photoelectron spectroscopy (XPS) measurements showed the oxidation of the surface due to the formation of carbonyl and carboxyl groups. Laser scanning microscopy revealed a surface roughening after the treatment. Contact angles of water and diiodomethane decreased significantly after the plasma treatment and the consecutively calculated surface free energy increased. Finally, two practical adhesion tests revealed an improvement of the applied acrylic dispersion coating’s adhesion to the WPC surface: The assigned cross-cut class improved, and the pull-off strength increased from 1.4 to 2.3 N/mm2