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Artificial adipose tissue (AT) constructs are urgently needed to treat severe wounds, to replace removed tissue, or for the use as in vitro model to screen for potential drugs or study metabolic pathways. The clinical translation of products is mostly prevented by the absence of a vascular component that would allow a sustainable maintenance and an extension of the construct to a relevant size. With this study, we aimed to evaluate the suitability of a novel material based on bacterial cellulose (CBM) on the defined adipogenic differentiation of human adipose-derived stem cells (ASCs) and the maintenance of the received adipocytes (diffASCs) and human microvascular endothelial cells (mvECs) in mono- and coculture. A slight acceleration of adipogenic differentiation over regular tissue culture polystyrene (TCPS) was seen on CBM under defined conditions, whereas on the maintenance of the generated adipocytes, comparable effects were detected for both materials. CBM facilitated the formation of vascular like structures in monoculture of mvECs, which was not observed on TCPS. By contrast, vascular-like structures were detected in CBM and TCPS in coculture by the presence of diffASCs. Concluding, CBM represents a promising material in vascularized AT engineering with the potential to speed up and simplify the in vitro setup of engineered products.
A new two-dimensional fluorescence sensor system was developed for in-line monitoring of mammalian cell cultures. Fluorescence spectroscopy allows for the detection and quantification of naturally occurring intra- and extracellular fluorophores in the cell broth. The fluorescence signals correlate the the cells' current redox state and other relevant process parameters. Cell culture pretests with twelve different excitation wavelengths showed that only three wavelengths account for a vast majority of spectral variation. Accordingly, the newly developed device utilizes three high-power LEDs as excitation sources in combination with a back-thinned CCD-spectrometer for fluorescence detection.
Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans.
It is known that the costs related with drug research and development (R&D) and the timelines to develop a new drug increased over the past years. In parallel, the success rates of drug projects along the pharmaceutical R&D phases are still very low, and the outcome of all R&D efforts is stagnating. In consequence, the R&D efficiency defined as the financial investment per drug has been steadily decreasing. As innovation is the major growth driver of the pharmaceutical industry, reliable data on R&D efficiency and new concepts to overcome these challenges are of great interest for R&D managers and the sustainability of the pharmaceutical industry as a whole. This book chapter reviews publications on R&D performance indicators of the past years, such as the success rates and timelines per phase. Additionally, it illustrates the factors influencing the success rates, timelines, and costs of pharmaceutical R&D most and, thus, the denominators of the R&D efficiency.
Tissue constructs of physiologically relevant scale require a vascular system to maintain cell viability. However, in vitro vascularization of engineered tissues is still a major challenge. Successful approaches are based on a feeder layer (FL) to support vascularization. Here, we investigated whether the supporting effect on the self‐assembled formation of prevascular‐like structures by microvascular endothelial cells (mvECs) originates from the FL itself or from its extracellular matrix (ECM). Therefore, we compared the influence of ECM, either derived from adipose‐derived stem cells (ASCs) or adipogenically differentiated ASCs, with the classical cell‐based FL. All cell‐derived ECM (cdECM) substrates enabled mvEC growth with high viability. Prevascular‐like structures were visualized by immunofluorescence staining of endothelial surface protein CD31 and could be observed on all cdECM and FL substrates but not on control substrate collagen I. On adipogenically differentiated ECM, longer and higher branched structures could be found compared with stem cell cdECM. An increased concentration of proangiogenic factors was found in cdECM substrates and FL approaches compared with controls. Finally, the expression of proteins associated with tube formation (E‐selectin and thrombomodulin) was confirmed. These results highlight cdECM as promising biomaterial for adipose tissue engineering by inducing the spontaneous formation of prevascular‐like structures by mvECs.
An advanced ‘clickECM’ that can be modified by the inverse-electron demand Diels-Alder reaction
(2021)
The extracellular matrix (ECM) represents the natural environment of cells in tissue and therefore is a promising biomaterial in a variety of applications. Depending on the purpose, it is necessary to equip the ECM with specific addressable functional groups for further modification with bioactive molecules, for controllable cross-linking and/or covalent binding to surfaces. Metabolic glycoengineering (MGE) enables the specific modification of the ECM with such functional groups without affecting the native structure of the ECM. In a previous approach (S. M. Ruff, S. Keller, D. E. Wieland, V. Wittmann, G. E. M. Tovar, M. Bach, P. J. Kluger, Acta Biomater. 2017, 52, 159–170), we demonstrated the modification of an ECM with azido groups, which can be addressed by bioorthogonal copper-catalyzed azide-alkyne cycloaddition (CuAAC). Here, we demonstrate the modification of an ECM with dienophiles (terminal alkenes, cyclopropene), which can be addressed by an inverse-electron-demand Diels-Alder (IEDDA) reaction. This reaction is cell friendly as there are no cytotoxic catalysts needed. We show the equipment of the ECM with a bioactive molecule (enzyme) and prove that the functional groups do not influence cellular behavior. Thus, this new material has great potential for use as a biomaterial, which can be individually modified in a wide range of applications.
Gelatin is one of the most prominent biopolymers in biomedical material research and development. It is frequently used in hybrid hydrogels, which combine the advantageous properties of bio‐based and synthetic polymers. To prevent the biological component from leaching out of the hydrogel, the biomolecules can be equipped with azides. Those groups can be used to immobilize gelatin covalently in hydrogels by the highly selective and specific azide–alkyne cycloaddition. In this contribution, we functionalized gelatin with azides at its lysine residues by diazo transfer, which offers the great advantage of only minimal side‐chain extension. Approximately 84–90% of the amino groups are modified as shown by 1H‐NMR spectroscopy, 2,4,6‐trinitrobenzenesulfonic acid assay as well as Fourier‐transform infrared spectroscopy, rheology, and the determination of the isoelectric point. Furthermore, the azido‐functional gelatin is incorporated into hydrogels based on poly(ethylene glycol) diacrylate (PEG‐DA) at different concentrations (0.6, 3.0, and 5.5%). All hydrogels were classified as noncyctotoxic with significantly enhanced cell adhesion of human fibroblasts on their surfaces compared to pure PEG‐DA hydrogels. Thus, the new gelatin derivative is found to be a very promising building block for tailoring the bioactivity of materials.
It is assumed that more education leads to better understanding of complex systems. Some researchers, however, find indications that simple mechanisms like stocks and flows are not well understood even by people who have passed higher education. In this paper, we test people’s understanding of complex systems with the widely studied stock-and-flow (SF) tasks. SF tasks assess people’s understanding of the interplay between stocks and flows. We investigate SF failure of domain experts and novices in different knowledge domains. In particular, we compare performance on the original study’s bathtub task with the square wave pattern with two alternative cover stories from the engineering and business domains on different groups of business and engineering students from different semesters. Further, we show that, while engineering students perform better than business students, with progressing in higher education, students may lose the capability of dealing with simple SF tasks. We thus find hints on déformation professionelle in higher education.
Due to its availability and minimal invasive harvesting human adipose tissue-derived extracellular matrix (dECM) is often used as a biomaterial in various tissue engineering and healthcare applications. Next to dECM, cell-derived ECM (cdECM) can be generated by and isolated from in vitro cultured cells. So far both types of ECM were investigated extensively toward their application as (bio)material in tissue engineering and healthcare. However, a systematic characterization and comparison of soft tissue dECM and cdECM is still missing. In this study, we characterized dECM from human adipose tissue, as well as cdECM from human adipose-derived stem cells, toward their molecular composition, structural characteristics, and biological purity. The dECM was found to exhibit higher levels of collagens and lower levels of sulfated glycosaminoglycans compared with cdECMs. Structural characteristics revealed an immature state of the fibrous part of cdECM samples. By the identified differences, we aim to support researchers in the selection of a suitable ECM-based biomaterial for their specific application and the interpretation of obtained results.
Different sensor types using chemical and biochemical principles are described. The former are mainly gas sensors, the latter are applied especially to liquids. Those label-free direct detection methods are compared with applications where assays take advantage of labeled receptors.
Furthermore, selected applications in the area of gas sensors are discussed, and sensors for process control, point-of-care diagnostics, environmental analytics, and food analytics are reviewed. In addition, multiplexing approaches used in microplates and microarrays are described.
On account of the huge number of sensor types and the wide range of possible applications, only the most important ones are selected here.
This article reviews the literature on Christmas economics. First, we present an overall picture of the debate on the potential welfare loss of gift-giving and we show strategies that reduce the potential welfare loss and might increase the number of presents received. Second, we discuss the effect of Christmas on prices and the business cycle. We provide evidence that at Christmas stock prices and airfares increase, while food prices decrease.
The dynamic capabilities perspective is aimed at explaining how firms achieve and sustain competitive advantages, especially in environments that become volatile, uncertain, complex, and ambiguous (VUCA). In this paper, we combine factors that explain dynamic capabilities on the firm level with factors of dynamic managerial capabilities on the individual level. In addition to the dynamic capabilities theory, we draw on corporate foresight (CF) literature to test the impact of CF training. We find that both the organizational-level practices and the individual-level training of leaders are positively associated with firm-level outcomes. We further observe that this relationship is mediated by dynamic managerial capabilities (i.e., the ability of leaders to challenge current business models, make decisions under uncertainty, and reconfigure organizational resources). Our findings emphasize the importance of training leaders and building organizational CF practices to build the dynamic capabilities needed in VUCA environments.
Plasma polymerization is used for the modification and control of surface properties of a highly transparent, thermoplastic elastomeric silicone copolymer, GENIOMER® 80 (G80). PEG-like diglyme plasma polymer films were deposited with ether retentions varying between 20% and 70% as measured by X-ray photoelectron spectroscopy analysis which did not affect the transparency of the substrate. Films with ether retentions of greater than 70% inhibit protein binding (bovine serum albumin and fibrinogen) and cell proliferation. A short oxygen plasma pretreatment enhances the adhesion and stability of the film as shown by protein binding and cell adhesion experiments. The transparency of the material and the stability of the coating makes this material a versatile bulk material for technical (e.g., lab-on-a-chip) and biomedical (e.g., intraocular lens) applications. The G80/plasma polymer composite is stable against vigorous washing and storage over 5 months and, therefore, offers an attractive alternative to poly(dimethylsiloxane).
In this study, a novel strategy has been developed for the assembly of polyelectrolyte multilayer (PEM) on CaCO3 templates in acidic pH solutions, where consecutive polyelectrolyte layers (heparin/poly(allylamine hydrochloride) or heparin/chitosan) were deposited on PEM hollow microcapsules established previously on CaCO3 templates. The PEM build-up, hollow capsule characterization and successful encapsulation of fluorescein 5(6)-isothiocyanate (FITC)-Dextran by coprecipitation with CaCO3 are demonstrated. Improvement by the removal of CaCO3 core was achieved while the depositions. In the course of the release profile, high retardation for encapsulated FITC-Dextran was observed. The combined shell capsules system is a significant trait that has potential use in tailoring functional layer-by-layer capsules as intelligent drug delivery vehicles where the preliminary in vitro tests showed the responsiveness on the enzymes.
The intelligent recycling of plastics waste is a major concern. Because of the widespread use of polyethylene terephtalate, considerable amounts of PET waste are generated that are ideally re-introduced into the material cycle by generating second generation products without loss of materials performance. Chemical recycling methods are often expensive and entail environmentally hazardous by-products. Established mechanical methods generally provide materials of reduced quality, leading to products of lower quality. These drawbacks can be avoided by the development of new recycling methods that provide materials of high quality in every step of the production cycle. In the present work, oligomeric ethylene terephthalate with defined degrees of polymerization and defined molecular weight is produced by melt-mixing PET with different quantities of adipic acid as an alternative pathway of recycling PET with respect to conventional methods, offering ecofriendly and economical aspects. Additionally, block-copolyesters of defined block length are designed from the oligomeric products.
This study examines the relevance of integrated reporting quality (IRQ) to capital markets. We investigate whether IRQ benefits capital market participants by improving a firm's information environment, using analyst earnings forecast accuracy as a proxy. Our study focuses specifically on companies that publish integrated reports on a voluntary basis. Based on a scoring model, we assess IRQ and its effects with data from 2015 to 2019 of 101 companies. The results indicate no significant relationship between IRQ and analyst earnings forecast accuracy. Thus, IRQ does not appear to improve a firm's information environment, at least not currently in a voluntary setting. Drawing on previous literature in the field, this study further concludes that integrated reporting (IR) in general has not yet reached its full potential in benefitting capital markets. Potential implications of our results are that the standard setters should work to improve the specificity and rigor of their guidelines, and analysts should become more involved in developing IR guidelines to make them more relevant to their information needs. IR seems to unfold its benefits better in mandatory settings, which could call for regulators to make IR mandatory.
In retail environments, consumers commonly evaluate products while standing on some type of flooring and concurrently being exposed to music; however, no study has examined the interaction of these two atmospheric cues. To bridge this gap, this research examines whether retailers can benefit from creating multisensory atmospheric congruent rather than incongruent retail environments of flooring and music. The results of an experiment in a real retail store reveal positive effects of multisensory congruent retail environments (e.g., soft music combined with soft flooring) on product evaluations. This study provides a new process explanation with consumers’ purchase-related self-confidence mediating these effects. Specifically, consumers in congruent rather than incongruent retail environments experience more purchase-related self confidence, which in turn leads to more favorable product evaluations. Furthermore, this study shows that consumers with a low rather than a high preference for haptic information are influenced more by multisensory atmospheric congruence when evaluating a product haptically.
In this article, liposome-based coatings aiming to control drug release from therapeutic soft contact lenses (SCLs) materials are analyzed. A PHEMA based hydrogel material loaded with levofloxacin is used as model system for this research. The coatings are formed by polyelectrolyte layers containing liposomes of 1,2-dimyristoyl-sn-glycero-3- phosphocholine (DMPC) and DMPC1cholesterol (DMPC1 CHOL). The effect of friction and temperature on the drug release is investigated. The aim of the friction tests is to simulate the blinking of the eyelid in order to verify if the SCLs materials coated with liposomes are able to keep their properties, in particular the drug release ability. It was observed that under the study conditions, friction did not affect significantly the drug release from the liposome coated PHEMA material. In contrast, increasing the temperature of release leads to an increase of the drug diffusion rate through the hydrogel. This phenomenon is recorded both in the control and in the coated samples.
Melamine formaldehyde (MF) resins are widely used for the gluing and surface coating of wood-based consumer products in the interior design of living environments. MF resins are especially relevant in decorative laminate applications because of their good performance-to-price ratio. In their industrial processing, an important intermediate state is the liquid MF prepolymer that is used for decorative paper impregnation. Here, the drying of impregnated papers is investigated with respect to premature curing. A new method to quantify water release upon drying that allows estimation of the degree of undesired precuring is described. Since curing proceeds via polycondensation, crosslinking brings about the release of water molecules. By thermogravimetric analysis (TGA), drying was studied in terms of water release due to physical drying (elimination of “dilution water”) and chemical crosslinking of the prepolymer to a three-dimensional MF network (elimination of chemically liberated water). The results obtained by TGA/IR spectroscopic analysis of the liberated volatiles show that the emission of water from b-stage MF can be clearly analytically separated into a physical (evaporation of dilution water) and a chemical (liberation via condensation) sequence. TGA experiments were correlated with curing experiments performed with differential scanning calorimetry (DSC) to estimate the residual crosslinking capacities of the impregnated papers. The drying conditions used during the preparation of impregnated decorative papers seemed to significantly affect their remaining reactivity only when harsh drying conditions were used. Upon heat exposure for prolonged time, precuring of the oligomer units results in a shift of the temperature maxima in TGA.