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- ItemA modular in vitro flow model to analyse blood-surface interactions under physiological conditions(Berlin : De Gruyter, 2021) Valtin, Juliane; Behrens, Stephan; Maitz, Manfred F.; Schmieder, Florian; Sonntag, Frank; Werner, CarstenNewly developed materials for blood-contacting devices need to undergo hemocompatibility testing to prove compliance with clinical requirements. However, many current in vitro models disregard the influence of flow conditions and blood exchange as it occurs in vivo. Here, we present a flow model which allows testing of blood-surface interactions under more physiological conditions. This modular platform consists of a triple-pump-chip and a microchannel-chip with a customizable surface. Flow conditions can be adjusted individually within the physiological range. A performance test with whole blood confirmed the hemocompatibility of our modular platform. Hemolysis was negligible, inflammation and hemostasis parameters were comparable to those detected in a previously established quasi-static whole blood screening chamber. The steady supply of fresh blood avoids secondary effects by nonphysiological accumulation of activation products. Experiments with three subsequently tested biomaterials showed results similar to literature and our own experience. The reported results suggest that our developed flow model allows the evaluation of blood-contacting materials under physiological flow conditions. By adjusting the occurring wall shear stress, the model can be adapted for selected test conditions.
- ItemCruciate Ligament Cell Sheets Can Be Rapidly Produced on Thermoresponsive poly(glycidyl ether) Coating and Successfully Used for Colonization of Embroidered Scaffolds(Basel : MDPI, 2021) Zahn, Ingrid; Stöbener, Daniel David; Weinhart, Marie; Gögele, Clemens; Breier, Annette; Hahn, Judith; Schröpfer, Michaela; Meyer, Michael; Schulze-Tanzil, GundulaAnterior cruciate ligament (ACL) cell sheets combined with biomechanically competent scaffolds might facilitate ACL tissue engineering. Since thermoresponsive polymers allow a rapid enzyme-free detachment of cell sheets, we evaluated the applicability of a thermoresponsive poly(glycidyl ether) (PGE) coating for cruciate ligamentocyte sheet formation and its influence on ligamentocyte phenotype during sheet-mediated colonization of embroidered scaffolds. Ligamentocytes were seeded on surfaces either coated with PGE or without coating. Detached ligamentocyte sheets were cultured separately or wrapped around an embroidered scaffold made of polylactide acid (PLA) and poly(lactic-co-ε-caprolactone) (P(LA-CL)) threads functionalized by gas-phase fluorination and with collagen foam. Ligamentocyte viability, protein and gene expression were determined in sheets detached from surfaces with or without PGE coating, scaffolds seeded with sheets from PGE-coated plates and the respective monolayers. Stable and vital ligamentocyte sheets could be produced within 24 h with both surfaces, but more rapidly with PGE coating. PGE did not affect ligamentocyte phenotype. Scaffolds could be colonized with sheets associated with high cell survival, stable gene expression of ligament-related type I collagen, decorin, tenascin C and Mohawk after 14 d and extracellular matrix (ECM) deposition. PGE coating facilitates ligamentocyte sheet formation, and sheets colonizing the scaffolds displayed a ligament-related phenotype.
- ItemDurable endothelium-mimicking coating for surface bioengineering cardiovascular stents([Bejing] : KeAi Publishing, 2021) Ma, Qing; Shi, Xiuying; Tan, Xing; Wang, Rui; Xiong, Kaiqin; Maitz, Manfred F.; Cui, Yuanyuan; Hu, Zhangmei; Tu, Qiufen; Huang, Nan; Shen, Li; Yang, ZhiluMimicking the nitric oxide (NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis (ISR) effectively. However, the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component. Herein, we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species (e.g., Cu-DOTA coordination complex) and glycocalyx-like component (e.g., heparin) to create a durable endothelium-mimicking surface. The stent surface was firstly coated with polydopamine (pDA), followed by a surface chemical cross-link with polyamine (pAM) to form a durable pAMDA coating. Using a stepwise grafting strategy, Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry. Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules, this proposed strategy could provide 62.4% bioactivity retention ratio of heparin, meanwhile persistently generate NO at physiological level from 5.9 ± 0.3 to 4.8 ± 0.4 × 10−10 mol cm−2 min−1 in 1 month. As a result, the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis, inflammation, and intimal hyperplasia, enhanced re-endothelialization, and hence efficiently reduced ISR.
- ItemIntelligent H2S release coating for regulating vascular remodeling(Bejing : KeAi Publishing, 2021) Lu, Bingyang; Han, Xiao; Zhao, Ansha; Luo, Dan; Maitz, Manfred F.; Wang, Haohao; Yang, Ping; Huang, NanCoronary atherosclerotic lesions exhibit a low-pH chronic inflammatory response. Due to insufficient drug release control, drug-eluting stent intervention can lead to delayed endothelialization, advanced thrombosis, and unprecise treatment. In this study, hyaluronic acid and chitosan were used to prepare pH-responsive self-assembling films. The hydrogen sulfide (H2S) releasing aspirin derivative ACS14 was used as drug in the film. The film regulates the release of the drug adjusted to the microenvironment of the lesion, and the drug balances the vascular function by releasing the regulating gas H2S, which comparably to NO promotes the self-healing capacity of blood vessels. Drug releasing profiles of the films at different pH, and other biological effects on blood vessels were evaluated through blood compatibility, cellular, and implantation experiments. This novel method of self-assembled films which H2S in an amount, which is adjusted to the condition of the lesion provides a new concept for the treatment of cardiovascular diseases.
- ItemPhoto-functionalized TiO2 nanotubes decorated with multifunctional Ag nanoparticles for enhanced vascular biocompatibility(Bejing : KeAi Publishing, 2021) Chen, Jiang; Dai, Sheng; Liu, Luying; Maitz, Manfred F.; Liao, Yuzhen; Cui, Jiawei; Zhao, Ansha; Yang, Ping; Huang, Nan; Wang, YunbingTitanium dioxide (TiO2) has a long history of application in blood contact materials, but it often suffers from insufficient anticoagulant properties. Recently, we have revealed the photocatalytic effect of TiO2 also induces anticoagulant properties. However, for long-term vascular implant devices such as vascular stents, besides anticoagulation, also anti-inflammatory, anti-hyperplastic properties, and the ability to support endothelial repair, are desired. To meet these requirements, here, we immobilized silver nanoparticles (AgNPs) on the surface of TiO2 nanotubes (TiO2-NTs) to obtain a composite material with enhanced photo-induced anticoagulant property and improvement of the other requested properties. The photo-functionalized TiO2-NTs showed protein-fouling resistance, causing the anticoagulant property and the ability to suppress cell adhesion. The immobilized AgNPs increased the photocatalytic activity of TiO2-NTs to enhances its photo-induced anticoagulant property. The AgNP density was optimized to endow the TiO2-NTs with anti-inflammatory property, a strong inhibitory effect on smooth muscle cells (SMCs), and low toxicity to endothelial cells (ECs). The in vivo test indicated that the photofunctionalized composite material achieved outstanding biocompatibility in vasculature via the synergy of photo-functionalized TiO2-NTs and the multifunctional AgNPs, and therefore has enormous potential in the field of cardiovascular implant devices. Our research could be a useful reference for further designing of multifunctional TiO2 materials with high vascular biocompatibility.
- ItemCross-Hemisphere Study Reveals Geographically Ubiquitous, Plastic-Specific Bacteria Emerging from the Rare and Unexplored Biosphere(Washington, DC : American Society for Microbiology, 2021) Scales, Brittan S.; Cable, Rachel N.; Duhaime, Melissa B.; Gerdts, Gunnar; Fischer, Franziska; Fischer, Dieter; Mothes, Stephanie; Hintzki, Lisa; Moldaenke, Lynn; Ruwe, Matthias; Kalinowski, Jörn; Kreikemeyer, Bernd; Pedrotti, Maria-Luiza; Gorsky, Gaby; Elineau, Amanda; Labrenz, Matthias; Oberbeckmann, Sonja; Campbell, Barbara J.While it is now appreciated that the millions of tons of plastic pollution travelling through marine systems carry complex communities of microorganisms, it is still unknown to what extent these biofilm communities are specific to the plastic or selected by the surrounding ecosystem. To address this, we characterized and compared the microbial communities of microplastic particles, nonplastic (natural and wax) particles, and the surrounding waters from three marine ecosystems (the Baltic, Sargasso and Mediterranean seas) using high-throughput 16S rRNA gene sequencing. We found that biofilm communities on microplastic and nonplastic particles were highly similar to one another across this broad geographical range. The similar temperature and salinity profiles of the Sargasso and Mediterranean seas, compared to the Baltic Sea, were reflected in the biofilm communities. We identified plastic-specific operational taxonomic units (OTUs) that were not detected on nonplastic particles or in the surrounding waters. Twenty-six of the plastic-specific OTUs were geographically ubiquitous across all sampled locations. These geographically ubiquitous plastic-specific OTUs were mostly low-abundance members of their biofilm communities and often represented uncultured members of marine ecosystems. These results demonstrate the potential for plastics to be a reservoir of rare and understudied microbes, thus warranting further investigations into the dynamics and role of these microbes in marine ecosystems.
- ItemFormer Training Relieves the Later Development of Behavioral Inflexibility in an Animal Model Overexpressing the Dopamine Transporter(Totowa, NJ : Humana Press, 2022) Edemann-Callesen, Henriette; Glienke, Maximilian; Akinola, Esther Olubukola; Lieser, Maike Kristin; Habelt, Bettina; Hadar, Ravit; Bernhardt, Nadine; Winter, ChristineA range of dopamine-dominating neuropsychiatric disorders present with cognitive deficits. In accordance, the dopamine transporter overexpressing rat model (DAT-tg rat) displays cognitive deficits by means of behavioral inflexibility and learning disabilities. It remains to be investigated when cognitive deficits emerge, due to the inherent DA irregularities, during the life course of the DAT-tg rat and what may relieve symptoms. The Morris water maze (MWM) was used to assess cognitive abilities in three cohorts of DAT-tg rats. In the first cohort, the development of cognitive deficits was assessed by repeatedly testing animals in the MWM at postnatal day (PND) 35, 60, and 90. In the second and third cohort, pharmacological interventions and transcranial direct current stimulation (tDCS) were tested in adult animals to understand what drives, and thus relieves, the deficits. Minor differences were observed between DAT-tg rats and control rats at PND 35 and 60, whereas cognitive deficits fully emerged at PND 90. A high dosage of methylphenidate diminished both behavioral inflexibility and improved learning abilities in adult rats. Interestingly, rats subjected early in life to the MWM also displayed improved behavioral flexibility as compared to rats naïve to the paradigm. Cognitive deficits gradually develop over time and fully emerge in adulthood. Pharmacological modulation of the ubiquitous DAT overexpression overall improves deficits in adult rats, whereas early training decreases later development of behavioral inflexibility. Thus, former training may constitute a preventive avenue that alters some aspects of cognitive deficits resulting from inherent DA abnormalities.
- ItemBlend Structure and n-Type Thermoelectric Performance of PA6/SAN and PA6/PMMA Blends Filled with Singlewalled Carbon Nanotubes(Basel : MDPI, 2021-4-28) Krause, Beate; Liguoro, Alice; Pötschke, PetraThe present study investigates how the formation of melt-mixed immiscible blends based on PA6/SAN and PA6/PMMA filled with single walled nanotubes (SWCNTs) affects the thermoelectric (TE) properties. In addition to the detailed investigation of the blend morphology with compositions between 100/0 wt.% and 50/50 wt.%, the thermoelectric properties are investigated on blends with different SWCNT concentrations (0.25–3.0 wt.%). Both PA6 and the blend composites with the used type of SWCNTs showed negative Seebeck coefficients. It was shown that the PA6 matrix polymer, in which the SWCNTs are localized, mainly influenced the thermoelectric properties of blends with high SWCNT contents. By varying the blend composition, an increase in the absolute Seebeck coefficient, power factor (PF), and figure of merit (ZT) was achieved compared to the PA6 composite which is mainly related to the selective localization and enrichment of SWCNTs in the PA6 matrix at constant SWCNT loading. The maximum PFs achieved were 0.22 µW/m·K2 for PA6/SAN/SWCNT 70/30/3 wt.% and 0.13 µW/m·K2 for PA6/PMMA/SWCNT 60/40/3 wt.% compared to 0.09 µW/m·K2 for PA6/3 wt.% SWCNT which represent increases to 244% and 144%, respectively. At higher PMMA or SAN concentration, the change from matrix-droplet to a co-continuous morphology started, which, despite higher SWCNT enrichment in the PA6 matrix, disturbed the electrical conductivity, resulting in reduced PFs with still increasing Seebeck coefficients. At SWCNT contents between 0.5 and 3 wt.% the increase in the absolute Seebeck coefficient was compensated by lower electrical conductivity resulting in lower PF and ZT as compared to the PA6 composites.
- ItemMultivalent Protein-Loaded pH-Stable Polymersomes: First Step toward Protein Targeted Therapeutics(Weinheim : Wiley-VCH, 2021) Moreno, Silvia; Boye, Susanne; Ajeilat, Hane George Al; Michen, Susanne; Tietze, Stefanie; Voit, Brigitte; Lederer, Albena; Temme, Achim; Appelhans, DietmarSynthetic platforms for mimicking artificial organelles or for designing multivalent protein therapeutics for targeting cell surface, extracellular matrix, and tissues are in the focus of this study. Furthermore, the availability of a multi-functionalized and stimuli-responsive carrier system is required that can be used for sequential in situ and/or post loading of different proteins combined with post-functionalization steps. Until now, polymersomes exhibit excellent key characteristics to fulfill those requirements, which allow specific transport of proteins and the integration of proteins in different locations of polymeric vesicles. Herein, different approaches to fabricate multivalent protein-loaded, pH-responsive, and pH-stable polymersomes are shown, where a combination of therapeutic action and targeting can be achieved, by first choosing two model proteins such as human serum albumin and avidin. Validation of the molecular parameters of the multivalent biohybrids is performed by dynamic light scattering, cryo-TEM, fluorescence spectroscopy, and asymmetrical flow-field flow fractionation combined with light scattering techniques. To demonstrate targeting functions of protein-loaded polymersomes, avidin post-functionalized polymersomes are used for the molecular recognition of biotinylated cell surface receptors. These versatile protein-loaded polymersomes present new opportunities for designing sophisticated biomolecular nanoobjects in the field of (extracellular matrix) protein therapeutics.
- ItemMaintenance of Ligament Homeostasis of Spheroid-Colonized Embroidered and Functionalized Scaffolds after 3D Stretch(Basel : Molecular Diversity Preservation International (MDPI), 2021) Gögele, Clemens; Konrad, Jens; Hahn, Judith; Breier, Annette; Schröpfer, Michaela; Meyer, Michael; Merkel, Rudolf; Hoffmann, Bernd; Schulze-Tanzil, GundulaAnterior cruciate ligament (ACL) ruptures are usually treated with autograft implantation to prevent knee instability. Tissue engineered ACL reconstruction is becoming promising to circumvent autograft limitations. The aim was to evaluate the influence of cyclic stretch on lapine (L) ACL fibroblasts on embroidered scaffolds with respect to adhesion, DNA and sulphated glycosaminoglycan (sGAG) contents, gene expression of ligament-associated extracellular matrix genes, such as type I collagen, decorin, tenascin C, tenomodulin, gap junctional connexin 43 and the transcription factor Mohawk. Control scaffolds and those functionalized by gas phase fluorination and cross-linked collagen foam were either pre-cultured with a suspension or with spheroids of LACL cells before being subjected to cyclic stretch (4%, 0.11 Hz, 3 days). Stretch increased significantly the scaffold area colonized with cells but impaired sGAGs and decorin gene expression (functionalized scaffolds seeded with cell suspension). Stretching increased tenascin C, connexin 43 and Mohawk but decreased decorin gene expression (control scaffolds seeded with cell suspension). Pre-cultivation of functionalized scaffolds with spheroids might be the more suitable method for maintaining ligamentogenesis in 3D scaffolds compared to using a cell suspension due to a significantly higher sGAG content in response to stretching and type I collagen gene expression in functionalized scaffolds.
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