INMdok (Leibniz Institute for New Materials)
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In vivo biocompatibility of a new hydrophobic coated Al/Al2O3 nanowire surface on stents
Full text linkBackground: Intima proliferation and in-stent restenosis is a challenging situation in interventional treatment of small vessel obstruction. Al/Al2O3 nanowires have been shown to accelerate vascular endothelial cell proliferation and migration in vitro, while suppressing vascular smooth muscle cell growth. Moreover, surface modification of Al/Al2O3 nanowires with poly[bis(2,2,2-trifluoromethoxy)phosphazene (PTFEP) coating enables further advantages such as reduced platelet adhesion. Therefore, the study's goal was to compare the biocompatibility of novel Al/Al2O3 + PTFEP coated nanowire bare-metal stents to uncoated control stents in vivo using optical coherence tomography (OCT), quantitative angiography and histomorphometric assessment. Methods: 15 Al/Al2O3 + PTFEP coated and 19 control stents were implanted in the cervical arteries of 9 Aachen minipigs. After 90 days, in-stent stenosis, thrombogenicity, and inflammatory response were assessed. Scanning electron microscopy was used to analyse the stent surface. Results: OCT analysis revealed that neointimal proliferation in Al/Al2O3 + PTFEP coated stents was significantly reduced compared to control stents. The neointimal area was 1.16 ± 0.77 mm2 in Al/Al2O3 + PTFEP coated stents vs. 1.98 ± 1.04 mm2 in control stents (p = 0.004), and the neointimal thickness was 0.28 ± 0.20 vs. 0.47 ± 0.10 (p = 0.003). Quantitative angiography showed a tendency to less neointimal growth in coated stents. Histomorphometry showed no significant difference between the two groups and revealed an apparent inflammatory reaction surrounding the stent struts. Conclusions: At long-term follow-up, Al/Al2O3 + PTFEP coated stents placed in peripheral arteries demonstrated good tolerance with no treatment-associated vascular obstruction and reduced in-stent restenosis in OCT. These preliminary in vivo findings indicate that Al/Al2O3 + PTFEP coated nanowire stents may have translational potential to be used for the prevention of in-stent restenosis
Direct monitoring of intracellular polymer degradation via BODIPY dynamic dequenching
Full text linkBiodegradable polymers play a crucial role in biomedical applications, particularly as nanocarriers in drug delivery. While labeling the polymers with fluorescent dyes facilitates monitoring their biodistribution and post cellular uptake, tracking polymer degradation within biological systems remains a challenge. This raises important unanswered questions regarding the fate of the polymers, their degradation products, and the degree of their degradation within biological systems. In this study, we developed a novel dynamic biodynamer (BDP-Lys) composed of BODIPY and lysine-hydrazide monomers linked by reversible dynamic covalent bonds, designed to control the fluorescence of BODIPY by degradation. The BDP-Lys undergoes pH-responsive degradation, leading to recovery of quenched BODIPY and enhanced fluorescence emissions, thereby enabling direct monitoring of intracellular polymer degradation. Physicochemical characterization revealed its molecular weight, filament-like morphology, and a notable 12-fold increase in fluorescence intensity at acid-induced degradation. In vitro studies demonstrated excellent biocompatibility, efficient cellular uptake and a threefold increase in fluorescence due to polymer degradation in mammalian cells, resulting in a maximum of 17 % monomer release in the first 24 h. Thus, BDP-Lys emerges as a promising tool for exploring polymer behavior in biological systems, providing real-time insights into degradation and offering new opportunities to address unresolved questions in the field
Multi‐Walled Carbon Nanotubes Suspensions as Liquid Conductors: Electrical and Mechanical Network Interplay
Full text linkAbstractSoft‐adaptive electronics require both sensor and conductor materials. The key parameter for these materials is their mechanoelectrical properties. Liquid metals and solid conductive composites have been exploited in this application field, but both are limited by either their chemical stability or limited flexibility, respectively. Electrofluids are a novel approach toward soft electronic components. They are concentrated colloidal suspensions of conductive particles, in which dynamic contacts retain electrical conductivity under deformation, filling the gap between liquid metals and solid composites. Here, the mechanical and electrical network interplay of electrofluids is studied based on multi‐walled carbon nanotubes (MWCNTs) in glycerol. These networks arise at different filler concentrations, showing a different response to external deformations. It is found that electrical conductivity occurs without the presence of a rigid mechanical network, which allows MWCNT suspensions to be electrically conductive even under flow conditions. By performing rheoelectrical measurements, the study observed how the mechanical and electrical networks evolve with the applied deformation. The study demonstrates the applicability of electrofluids with tailored mechanoelectrical properties as soft electrical connectors
An Engineered Living Material with pro-angiogenic activity inducible by near-infrared light
No full textImpaired angiogenesis is a central barrier in the treatment of chronic and deep tissue wounds, preventing progression through the normal healing cascade. While the combination of near-infrared (NIR) photobiomodulation and pro-angiogenic growth factors has shown synergistic therapeutic benefit, the clinical translation of growth factor therapy is hindered by high cost, instability and the need for localized dosing to avoid aberrant vasculature. Peptidomimetics such as the VEGF-derived QK peptide offer a more stable and predictable alternative, but still require a means for localized, tunable presentation. Here, we establish an engineered living material based delivery system that responds to clinically relevant NIR light to produce and releases a QK-Fusion protein directly at the target site. The probiotic Escherichia coli Nissle 1917 was engineered with an 800 nm-responsive optogenetic circuit and encapsulated within an optimized alginate core–shell hydrogel that ensures biocontainment while allowing controlled outward diffusion of the secreted peptide. The released peptide remains non-cytotoxic and capable of binding extracellular matrix analogs and promoting the formation of organized, branched capillary-like networks in endothelial cultures. We thus establish a strategy for developing engineered living materials towards remote-controlled angiogenic stimulation
Signal-Amplifying Biohybrid Material Circuits for CRISPR/Cas-Based Single-Stranded RNA Detection
Full text linkThe functional integration of biological switches with synthetic building blocks enables the design of modular, stimulus-responsive biohybrid materials. By connecting the individual modules via diffusible signals, information-processing circuits can be designed. Such systems are, however, mostly limited to respond to either small molecules, proteins, or optical input thus limiting the sensing and application scope of the material circuits. Here, a highly modular biohybrid material is design based on CRISPR/Cas13a to translate arbitrary single-stranded RNAs into a biomolecular material response. This system exemplified by the development of a cascade of communicating materials that can detect the tumor biomarker microRNA miR19b in patient samples or sequences specific for SARS-CoV. Specificity of the system is further demonstrated by discriminating between input miRNA sequences with single-nucleotide differences. To quantitatively understand information processing in the materials cascade, a mathematical model is developed. The model is used to guide systems design for enhancing signal amplification functionality of the overall materials system. The newly designed modular materials can be used to interface desired RNA input with stimulus-responsive and information-processing materials for building point-of-care suitable sensors as well as multi-input diagnostic systems with integrated data processing and interpretation
Synthetic cells in tissue engineering
Full text linkTissue functions rely on complex structural, biochemical, and biomechanical cues that guide cellular behavior and organization. Synthetic cells, a promising new class of biomaterials, hold significant potential for mimicking these tissue properties using simplified, nonliving building blocks. Advanced synthetic cell models have already shown utility in biotechnology and immunology, including applications in cancer targeting and antigen presentation. Recent bottom-up approaches have also enabled synthetic cells to assemble into 3D structures with controlled intercellular interactions, creating tissue-like architectures. Despite these advancements, challenges remain in replicating multicellular behaviors and dynamic mechanical environments. Here, we review recent advancements in synthetic cell-based tissue formation and introduce a three-pillar framework to streamline the development of synthetic tissues. This approach, focusing on synthetic extracellular matrix integration, synthetic cell self-organization, and adaptive biomechanics, could enable scalable synthetic tissues engineering for regenerative medicine and drug development
Optimized Preparation and Potential Range for Spinel Lithium Titanate Anode for High-Rate Performance Lithium-Ion Batteries
Full text linkThe significant demand for energy storage systems has spurred innovative designs and extensive research on lithium-ion batteries (LIBs). To that end, an in-depth examination of utilized materials and relevant methods in conjunction with comparing electrochemical mechanisms is required. Lithium titanate (LTO) anode materials have received substantial interest in high-performance LIBs for numerous applications. Nevertheless, LTO is limited due to capacity fading at high rates, especially in the extended potential range of 0.01–3.00 V versus Li+/Li, while delivering the theoretical capacity of 293 mAh g−1. This study demonstrates how the performance of the LTO anode can be improved by modifying the manufacturing process. Altering the dry and wet mixing duration and speeds throughout the manufacturing process leads to differences in particle sizes and homogeneity of dispersion and structure. The optimized anode at 5 A g−1 (≈17C) and 10 A g−1 (≈34C) yielded 188 and 153 mAh g−1 and retained 73% and 68% of their initial capacity after 1000 cycles, respectively. The following findings offer valuable information regarding the empirical modifications required during electrode fabrication. Additionally, it sheds light on the potential to produce efficient anodes using commercial LTO powder
Evaluating cytocompatibility and biosafety of living biomaterials for ocular use
Full text linkLiving biomaterials are promising drug delivery and biosensor devices but their living character complicates their assessment with host tissues. Besides, the use of animal experiments increases complexity for preclinical assessment of these devices. In vitro systems applied specifically to living biomaterials are required to bridge this gap. Currently, these in vitro systems make use of immortalized cell lines and study very early timepoints (max. 72 h). Here, we report on an in vitro model for co-cultures of living biomaterials and corneal cells to study the cytocompatibility of living biomaterials applied to the eye. For this purpose, we encapsulated Corynebacterium glutamicum in polyvinyl alcohol hydrogels, used as a model of living biomaterial, and cultured them with human primary corneal cells (epithelial and keratocytes) for 7 days. We studied bacterial proliferation, biocontainment, biosafety, and glucose consumption. We also investigated potential cytotoxicity and pro-inflammatory responses of corneal cells to the living biomaterials. Results revealed that the bacterial hydrogels did not trigger any cytotoxicity or pro-inflammatory phenotype on corneal cells during the 7-day co-culture. Finally, we placed the bacterial hydrogels directly on top of matured corneal epithelium at the air-liquid interface, where no cytotoxic effects were observed. Overall, these findings highlight the potential of in vitro investigations for living biomaterials and the applicability of these devices for ophthalmology purposes
Water-Induced Transparency Loss in Styrene Butadiene Block Copolymers: Mechanism, Morphology, and Predictive Modeling
Full text linkWater-induced transparency loss in styrene–butadiene block copolymers (SBCs) has been investigated under a variety of conditions. Consistent with earlier work on homopolymers, the opacity after prolonged water exposure is expected to be caused by water clustering, which results from stronger water–water than water–polymer interactions. The water clusters distort the surrounding polymer matrix, causing local changes in the refractive index. It was found that the hard phase has only a minor contribution to the transparency loss, while the rubbery phase appears to be the major contributor. However, the loss of transparency was found not to be directly proportional to the volume of the soft phase, and a significant effect of the block copolymer morphology was observed, which was confirmed by a series of transmission electron microscopy and SAXS measurements. This effect is particularly evident in the transition from a continuous hard phase through a co-continuous morphology to a continuous soft phase. The acquired insights were subsequently used to predict long-term optical performance in SBCs to provide a tool in product development. Loss of transparency predictions was proven to be adequate through a classical regression-extrapolation approach using a limited data set, accurately simulating performance beyond 2600 h exposure time using only 600 h of measurement time. Additionally, it was shown that artificial neural networks could provide a solid tool in predicting performance even prior to synthesis, granted that the selection of descriptors is complete and the appropriate amount of data is supplied with a proper spread over the descriptor space
Laminar Flow Alters EV Composition in HUVECs: A Study of Culture Medium Optimization and Molecular Profiling of Vesicle Cargo
Full text linkEndothelial cells (ECs) experience shear stress associated with blood flow. Such shear stress regulates endothelial function by altering cell physiology. Since most cell culture protocols and media compositions are designed for static cultures and experiments with ECs are predominantly conducted under these non‐physiological conditions, a model for culturing ECs under flow conditions is developed, which more closely mimics their physiological environment. This approach also enables the isolation of EVs while minimizing FCS‐derived contaminants. In this study, a comprehensive assessment of how physiologically relevant cultivation conditions influence the vesicle composition and function of ECs is provided. A detailed investigation is conducted for the effect of different cell culture media on morphology and marker expression of human umbilical cord endothelial cells (HUVECs) and EVs, and optimize the conditions to culture ECs under flow, tailoring them specifically to facilitate the efficient isolation of EVs using a hollow‐fiber system model. These EVs are then characterized and compared to those isolated from traditional static culture conditions. Overall, this study presents a model on isolating EC‐derived EVs under conditions that closely mimic physiological environments, and characterization at their proteome, gene expression, and microRNA profile