Characterization of poly(glycolide-co-D,L-lactide)/poly(D,L-lactide) microspheres for controlled release of GM-CSF

PURPOSE: This study describes the preparation and characterization of a controlled release formulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) encapsulated in poly(glycolide-co-D,L-lactide) (PLGA) and poly(D,L-lactide) (PLA) microspheres. METHODS: GM-CSF was encapsulated in PLGA/PLA microspheres by a novel silicone oil based phase separation process. Several different blends of PLGA and low molecular weight PLA were used to prepare the microspheres. The microspheres and the encapsulated GM-CSF were extensively characterized both in vitro and in vivo. RESULTS: Steady release of GM-CSF was achieved over a period of about one week without significant "burst" of protein from the microspheres. Analysis of microsphere degradation kinetics by gel permeation chromatography (GPC) indicated that low molecular weight PLA enhanced the degradation of the PLGA and thereby affected release kinetics. GM-CSF released from the microspheres was found to be biologically active and physically intact by bioassay and chromatographic analysis. Analysis of serum from mice receiving huGM-CSF indicated that the GM-CSF was biologically active and that a concentration of greater than 10 ng/mL was maintained for a period lasting at least nine days. MuGM-CSF was not detected following in vivo administration of muGM-CSF microspheres. The tissues of mice receiving muGM-CSF microspheres were characterized by infiltration of neutrophils, and macrophages which were in significant excess of those found in mice administered with placebo controls (i.e. microspheres without GM-CSF). CONCLUSIONS: This study demonstrates the influence of formulation parameters on the encapsulation of GM-CSF in PLGA/PLA microspheres and its controlled release in biologically active form. The intense local tissue reaction in mice to muGM-CSF microspheres demonstrates the importance of the mode of delivery on the pharmacologic activity of GM-CSF.     

Thermoplastic Polyurethane Elastomers with Aliphatic Hard Segments Based on Plant‐Oil‐Derived Long‐Chain Diisocyanates

Novel plant‐oil‐derived long‐chain (C₁₉ and C₂₃) α,ω‐diisocyanates, optionally in combination with the corresponding long‐chain diols, provide entirely aliphatic hard segments in segmented thermoplastic polyurethane elastomers (TPUs), with carbohydrate‐based poly(trimethylene glycol) soft segments. Compared to materials based on a mid‐chain monomer analog, phase separation is higher due to an increased flexibility of the aliphatic segments. Although melting points are slightly lower than for HDPE, the long‐chain TPU's solid‐state structure is still dominated by hydrogen‐bonding.     

Predicting the potential of production structure changes using characteristic curves

Competitive market environments force manufacturing companies to achieve a high adherence to logistical targets. As their improvement potential is limited by the production structure, projects to modify machine-segment allocation are usually initiated using variant generation and qualitative evaluation methods which are neither able to identify optimal solutions nor to give an overview of possible performances. Furthermore, these projects are normally initiated to address the urgent need of change instead of organized opportunity management. This article presents a methodology for a high-level evaluation of the entire spectrum of possible production structures resulting in characteristic curves to display the progression of costs and logistical performance. Based on usually available master data of manufacturing companies, this approach allows continuous monitoring. The approach, consisting of the steps production structure generation, simulation and visualization, is validated using a real industry case from the machinery and plant engineering industry.     

Sliding wear of nanocrystalline Ni–W: Structural evolution and the apparent breakdown of Archard scaling

Sliding wear of nanocrystalline Ni–W alloys with grain sizes of 3–47 nm, a range which spans the transition in deformation mechanisms from intra- to inter-granular, has been studied through pin-on-disk wear testing. The extreme conditions produced during sliding wear are found to result in structural evolution and a deviation from Archard scaling for the finest grain sizes; in the finest nanocrystalline materials wear resistance is higher than would be expected based on hardness alone. The repetitive sliding load is found to lead to a modest amount of grain growth and grain boundary relaxation, which in turn leads to local hardening in the wear track. Analysis of the dynamic microstructure suggests that it is produced primarily as a result of local plasticity and is not principally due to frictional heating.     

Technology roadmapping for the production in high-wage countries

Manufacturing companies from high-wage countries must focus on future markets and products to remain competitive and to ensure long-term success. In a dynamic, global environment it is necessary to further improve the underlying production technologies and methodologies to achieve sustainable competitive advantages. Thus, a technology roadmap for advanced production technologies and approaches has been developed. The roadmap provides an overview of relevant technologies and their technological readiness. It points out challenges which manufacturing companies in high-wage countries have to face. Moreover, the applied roadmapping process is used to align the research activities within the Cluster of Excellence “Integrative Production Technology for High-Wage Countries” to the relevant topics concerning the cluster’s four main research areas, namely the individualized, virtual, hybrid and self-optimizing production. This paper describes the roadmapping process as well as its main results. Regarding each of the four research fields, a technology radar including exemplary technologies evaluated e.g., by their state of development is presented. Furthermore, relevant challenges, future trends and scientific tasks are discussed as main drivers influencing the cluster’s research activities.     

The uncorrelated triple junction distribution function: Towards grain boundary network design

Triple junctions are recognized as important microstructural features in the context of grain boundary network topology and grain boundary sensitive materials properties. In spite of this prominence, mathematical tools for quantifying distributions of misorientations around triple junctions have been limited to special cases. Here we derive a general formula for the uncorrelated triple junction distribution function (TJDF) for materials of arbitrary texture. Additionally, we provide the mathematical link between TJDF and the orientation distribution function, which should facilitate the use of materials design paradigms on the grain boundary network.     

Formation of nanostructures in a heterojunction with a deeply located 2D electron gas via the method of high-voltage anodic-oxidation lithography using an atomic-force microscope

A technique of high-voltage local anodic oxidation of the surfaces of Ga[Al]As-based heterostructures with the use of an atomic-force microscope is described. The application of a pulsed voltage and use of semicontact operating regime of the atomic-force microscope allowed obtainment of a locally depleted 2D electron gas (2DEG) at an unusually large depth of 80 nm from the surface. This circumstance makes it possible to create 2DEG-based ballistic nanostructures characterized by a high mobility of carriers. The technique of preparing an open quantum dot in the 2DEG with a mobility of μ ≈ 3 × 10⁶ cm²/(V s) at 4.2 K is described and the results of low-temperature test measurements of its conductivity are presented.     

Advances in ingredient and processing systems for meat and meat products

Changes in consumer demand of meat products as well as increased global competition are causing an unprecedented spur in processing and ingredient system developments within the meat manufacturing sector. Consumers demand healthier meat products that are low in salt, fat, cholesterol, nitrites and calories in general and contain in addition health-promoting bioactive components such as for example carotenoids, unsaturated fatty acids, sterols, and fibers. On the other hand, consumers expect these novel meat products with altered formulations to taste, look and smell the same way as their traditionally formulated and processed counterparts. At the same time, competition is forcing the meat processing industry to use the increasingly expensive raw material “meat” more efficiently and produce products at lower costs. With these changes in mind, this article presents a review of novel ingredient systems and processing approaches that are emerging to create high quality, affordable meat products not only in batch mode but also in large-scale continuous processes. Fat replacers, fat profile modification and cholesterol reduction techniques, new texture modifiers and alternative antioxidant and antimicrobial systems are being discussed. Modern processing equipment to establish continuously operating product manufacturing lines and that allow new meat product structures to be created and novel ingredients to be effectively utilized including vacuum fillers, grinders and fine dispersers, and slicers is reviewed in the context of structure creation in meat products. Finally, trends in future developments of ingredient and processing systems for meat products are highlighted.