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You are researching: Bayreuth University
Cell Type
Tissue and Organ Biofabrication
Skin Tissue Engineering
Drug Delivery
Biological Molecules
Solid Dosage Drugs
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Personalised Pharmaceuticals
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Drug Discovery
Cancer Cell Lines
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- Review Paper
- Printing Technology
- Biomaterial
- Non-cellularized gels/pastes
- Carbopol
- Epoxy
- poly (ethylene-co -vinyl acetate) (PEVA)
- Poly(itaconate-co-citrate-cooctanediol) (PICO)
- Poly(N-isopropylacrylamide) (PNIPAAm)
- Mineral Oil
- poly(octanediol-co-maleic anhydride-co-citrate) (POMaC)
- Poly(Oxazoline)
- Poly(trimethylene carbonate)
- 2-hydroxyethyl) methacrylate (HEMA)
- Zein
- Acrylamide
- Pluronic – Poloxamer
- Polyisobutylene
- Paraffin
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- Konjac Gum
- Polyphenylene Oxide
- Ionic Liquids
- Polyvinylpyrrolidone (PVP)
- Gelatin-Sucrose Matrix
- Salt-based
- Chlorella Microalgae
- Acrylates
- Poly(Vinyl Formal)
- 2-hydroxyethyl-methacrylate (HEMA)
- Phenylacetylene
- Magnetorheological fluid (MR fluid – MRF)
- Salecan
- Poly(vinyl alcohol) (PVA)
- PEDOT
- Jeffamine
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- Methacrylated hyaluronic acid (HAMA)
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- Chitosan
- Glycerol
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- Alginate
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- methacrylated chondroitin sulfate (CSMA)
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- Institution
- University of Manchester
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AUTHOR
Year
2023
Journal/Proceedings
Small Structures
Reftype
DOI/URL
DOI
Groups
AbstractHerein, the fabrication of light-sensitive high-aspect ratio surfaces with switchable topography using melt-electrowriting of shape-memory polymers and deposition of light-to-heat converting black ink on it by dip coating is reported on. The lamellae exposed to low temperatures are hard and cannot be deformed by water droplets. The temperature reached upon illumination of surfaces is close to the melting point of the soft segment of the polyurethane that leads to softening of the polymer. Due to this, it is possible to locally deform and recover the light-softened surface structures by water droplets deposited on lamellae. The deformed state can be fixed by cooling down resulting in the crystallization of the polymer. Thus, the reversibility of local deformation can be achieved. Finally, the application of the developed approach and materials for the fabrication of smart light-controlled valves is demonstrated, which can be used for the controlled mixing of fluids in microfluidic devices.
AUTHOR
Title
Fabrication of Hydrogel-Based Composite Fibers and Computer Simulation of the Filler Dynamics in the Composite Flow
[Abstract]
Year
2023
Journal/Proceedings
Bioengineering
Reftype
Groups
AbstractFibrous structures with anisotropic fillers as composites have found increasing interest in the field of biofabrication since they can mimic the extracellular matrix of anisotropic tissues such as skeletal muscle or nerve tissue. In the present work, the inclusion of anisotropic fillers in hydrogel-based filaments with an interpenetrating polymeric network (IPN) was evaluated and the dynamics of such fillers in the composite flow were analyzed using computational simulations. In the experimental part, microfabricated rods (200 and 400 μm length, 50 μm width) were used as anisotropic fillers in extrusion of composite filaments using two techniques of wet spinning and 3D printing. Hydrogels such as oxidized alginate (ADA) and methacrylated gelatin (GelMA) were used as matrices. In the computational simulation, a combination of computational fluid dynamics and coarse-grained molecular dynamics was used to study the dynamics of rod-like fillers in the flow field of a syringe. It showed that, during the extrusion process, microrods are far from being well aligned. Instead, many of them tumble on their way through the needle leading to a random orientation in the fiber which was confirmed experimentally.
AUTHOR
Title
Synthesis and Exfoliation of Calcium Organophosphonates for Tailoring Rheological Properties of Sodium Alginate Solutions: A Path toward Polysaccharide-Based Bioink
[Abstract]
Year
2023
Journal/Proceedings
Biomacromolecules
Reftype
DOI/URL
DOI
Groups
AbstractLayered nanoparticles with surface charge are explored as rheological modifiers for extrudable materials, utilizing their ability to induce electrostatic repulsion and create a house-of-cards structure. These nanoparticles provide mechanical support to the polymer matrix, resulting in increased viscosity and storage modulus. Moreover, their advantageous aspect ratio allows for shear-induced orientation and decreased viscosity during flow. In this work, we present a synthesis and liquid-based exfoliation procedure of phenylphosphonate-phosphate particles with enhanced ability to be intercalated by hydrophilic polymers. These layered nanoparticles are then tested as rheological modifiers of sodium alginate. The effective rheological modification is proved as the viscosity increases from 101 up to 103 Pa·s in steady state. Also, shear-thinning behavior is observed. The resulting nanocomposite hydrogels show potential as an extrudable bioink for 3D printing in tissue engineering and other biomedical applications, with good shape fidelity, nontoxicity, and satisfactory cell viability confirmed through encapsulation and printing of mouse fibroblasts.
AUTHOR
Year
2022
Journal/Proceedings
Advanced Materials Technologies
Reftype
DOI/URL
DOI
Groups
AbstractAbstract 4D Biofabrication – a pioneering biofabrication technique – involves the automated fabrication of 3D constructs that are dynamic and show shape-transformation capability. Although current 4D biofabrication methods are highly promising for the fabrication of vascular elements such as tubes, the fabrication of tubular junctions is still highly challenging. Here, for the first time, a 4D biofabrication-based concept for the fabrication of a T-shaped vascular bifurcation using 3D printed shape-changing layers based on a mathematical model is reported. The formation of tubular structures with various diameters is achieved by precisely controlling the parameters (e.g. crosslinking time). Consequently, the 3D printed films show self-transformation into a T-junction upon immersion in water with a diameter of a few millimeters. Perfusion of the tubular T-junction with an aqueous medium simulating blood flow through vessels shows minimal leakages with a maximum flow velocity of 0.11 m s–1. Furthermore, human umbilical vein endothelial cells seeded on the inner surface of the plain T-junction show outstanding growth properties and excellent cell viability. The achieved diameters are comparable to the native blood vessels, which is still a challenge in 3D biofabrication. This approach paves the way for the fabrication of fully automatic self-actuated vascular bifurcations as vascular grafts.
AUTHOR
Title
Flow Simulation and Gradient Printing of Fluorapatite- and Cell-Loaded Recombinant Spider Silk Hydrogels
[Abstract]
Year
2022
Journal/Proceedings
Biomolecules
Reftype
Groups
AbstractHierarchical structures are abundant in almost all tissues of the human body. Therefore, it is highly important for tissue engineering approaches to mimic such structures if a gain of function of the new tissue is intended. Here, the hierarchical structures of the so-called enthesis, a gradient tissue located between tendon and bone, were in focus. Bridging the mechanical properties from soft to hard secures a perfect force transmission from the muscle to the skeleton upon locomotion. This study aimed at a novel method of bioprinting to generate gradient biomaterial constructs with a focus on the evaluation of the gradient printing process. First, a numerical approach was used to simulate gradient formation by computational flow as a prerequisite for experimental bioprinting of gradients. Then, hydrogels were printed in a single cartridge printing set-up to transfer the findings to biomedically relevant materials. First, composites of recombinant spider silk hydrogels with fluorapatite rods were used to generate mineralized gradients. Then, fibroblasts were encapsulated in the recombinant spider silk-fluorapatite hydrogels and gradually printed using unloaded spider silk hydrogels as the second component. Thereby, adjustable gradient features were achieved, and multimaterial constructs were generated. The process is suitable for the generation of gradient materials, e.g., for tissue engineering applications such as at the tendon/bone interface.
AUTHOR
Title
Recombinant Spider Silk Bioinks for Continuous Protein Release by Encapsulated Producer Cells
[Abstract]
Year
2022
Journal/Proceedings
Biomacromolecules
Reftype
DOI/URL
DOI
Groups
AbstractTargeted therapies using biopharmaceuticals are of growing clinical importance in disease treatment. Currently, there are several limitations of protein-based therapeutics (biologicals), including suboptimal biodistribution, lack of stability, and systemic side effects. A promising approach to overcoming these limitations could be a therapeutic cell-loaded 3D construct consisting of a suitable matrix component that harbors producer cells continuously secreting the biological of interest. Here, the recombinant spider silk proteins eADF4(C16), eADF4(C16)-RGD, and eADF4(C16)-RGE have been processed together with HEK293 producer cells stably secreting the highly traceable reporter biological TNFR2-Fc-GpL, a fusion protein consisting of the extracellular domain of TNFR2, the Fc domain of human IgG1, and the luciferase of Gaussia princeps as a reporter domain. eADF4(C16) and eADF4(C16)-RGD hydrogels provide structural and mechanical support, promote HEK293 cell growth, and allow fusion protein production by the latter. Bioink-captured HEK293 producer cells continuously release functional TNFR2-Fc-GpL over 14 days. Thus, the combination of biocompatible, printable spider silk bioinks with drug-producing cells is promising for generating implantable 3D constructs for continuous targeted therapy.
AUTHOR
Title
Smart Mechanically Tunable Surfaces with Shape Memory Behavior and Wetting-Programmable Topography
[Abstract]
Year
2022
Journal/Proceedings
ACS Appl. Mater. Interfaces
Reftype
DOI/URL
DOI
Groups
AbstractThis paper reports for the first time the fabrication and investigation of wetting properties of structured surfaces formed by lamellae with an exceptionally high aspect ratio of up to 57:1 and more. The lamellar surfaces were fabricated using a polymer with tunable mechanical properties and shape-memory behavior. It was found that wetting properties of such structured surfaces depend on temperature, and thermal treatment history-structured surfaces are wetted easier at elevated temperature or after cooling to room temperature when the polymer is soft because of the easier deformability of lamellae. The shape of lamellae deformed by droplets can be temporarily fixed at low temperature and remains fixed upon heating to room temperature. Heating above the transition temperature of the shape-memory polymer restores the original shape. The high aspect ratio allows tuning of geometry not only manually, as it is done in most works reported previously but can also be made by a liquid droplet and is controlled by temperature. This behavior opens new opportunities for the design of novel smart elements for microfluidic devices such as smart valves, whose state and behavior can be switched by thermal stimuli: valves that can or cannot be opened that are able to close or can be fixed in an open or closed states.
AUTHOR
Title
Impact of Cell Loading of Recombinant Spider Silk Based Bioinks on Gelation and Printability
[Abstract]
Year
2021
Journal/Proceedings
Macromolecular Bioscience
Reftype
DOI/URL
DOI
Groups
AbstractAbstract Printability of bioinks encompasses considerations concerning rheology and extrudability, characterization of filament formation, shape fidelity, cell viability and post-printing cellular development. Recombinant spider silk based hydrogels might be a suitable material to be used in bioinks, i.e. a formulation of cells and materials to be used for bioprinting. Here, the high shape fidelity of spider silk ink is shown by bioprinting the shape and size of a human aortic valve. Further the influence of the encapsulation of cells has been evaluated on spider silk hydrogel formation, hydrogel mechanics, and shape fidelity upon extrusion based bioprinting. It is shown that the presence of cells impacts gelation of spider silk proteins differently depending on the used silk variant. RGD-modified spider silk hydrogels are physically crosslinked by the cells, while there is no active interaction between cells and un-tagged spider silk proteins. Strikingly, even at cell densities up to ten million cells/ml, cell viability is high after extrusion based printing which is a significant prerequisite for future applications. Shape fidelity of the printed constructs is demonstrated using a filament collapse test in absence and presence of human cells. This article is protected by copyright. All rights reserved
AUTHOR
Year
2018
Journal/Proceedings
ACS Biomaterials Science and Engineering
Reftype
DOI/URL
DOI
Groups
AbstractTherapeutic biologics (i.e., proteins) have been widely recognized for the treatment, prevention, and cure of a variety of human diseases and syndromes. However, design of novel protein-delivery systems to achieve a nontoxic, constant, and efficient delivery with minimal doses of therapeutic biologics is still challenging. Here, recombinant spider silk-based materials are employed as a delivery system for the administration of therapeutic biologicals. Hydrogels made of the recombinant spider silk protein eADF4(C16) were used to encapsulate the model biologicals BSA, HRP, and LYS by direct loading or through diffusion, and their release was studied. Release of model biologicals from eADF4(C16) hydrogels is in part dependent on the electrostatic interaction between the biological and the recombinant spider silk protein variant used. In addition, tailoring the pore sizes of eADF4(C16) hydrogels strongly influenced the release kinetics. In a second approach, a particles-in-hydrogel system was used, showing a prolonged release in comparison with that of plain hydrogels (from days to week). The particle-enforced spider silk hydrogels are injectable and can be 3D printed. These initial studies indicate the potential of recombinant spider silk proteins to design novel injectable hydrogels that are suitable for delivering therapeutic biologics.
AUTHOR
Title
Characterization of Hydrogels Made of a Novel Spider Silk Protein eMaSp1s and Evaluation for 3D Printing
[Abstract]
Year
2017
Journal/Proceedings
Macromolecular Bioscience
Reftype
DOI/URL
DOI
Groups
AbstractRecombinantly produced spider silk proteins have high potential for bioengineering and various biomedical applications because of their biocompatibility, biodegradability, and low immunogenicity. Here, the recently described small spider silk protein eMaSp1s is assembled into hydrogels, which can be 3D printed into scaffolds. Further, blending with a recombinantly produced MaSp2 derivative eADF4(C16) alters the mechanical properties of the resulting hydrogels. Different spider silk hydrogels also show a distinct recovery after a high shear stress deformation, exhibiting the tunability of their features for selected applications.
AUTHOR
Year
2017
Journal/Proceedings
Biofabrication
Reftype
DOI/URL
URL
Groups
AbstractBioinks, 3D cell culture systems which can be printed, are still in the early development stages. Currently, extensive research is going into designing printers to be more accommodating to bioinks, designing scaffolds with stiff materials as support structures for the often soft bioinks, and modifying the bioinks themselves. Recombinant spider silk proteins, a potential biomaterial component for bioinks, have high biocompatibility, can be processed into several morphologies and can be modified with cell adhesion motifs to enhance their bioactivity. In this work, thermally gelled hydrogels made from recombinant spider silk protein encapsulating mouse fibroblast cell line BALB/3T3 were prepared and characterized. The bioinks were evaluated for performance in vitro both before and after printing, and it was observed that unprinted bioinks provided a good platform for cell spreading and proliferation, while proliferation in printed scaffolds was prohibited. To improve the properties of the printed hydrogels, gelatin was given as an additive and thereby served indirectly as a plasticizer, improving the resolution of printed strands. Taken together, recombinant spider silk proteins and hydrogels made thereof show good potential as a bioink, warranting further development.
AUTHOR
Year
2015
Journal/Proceedings
Angewandte Chemie International Edition
Reftype
DOI/URL
DOI
Groups
AbstractBiofabrication is an emerging and rapidly expanding field of research in which additive manufacturing techniques in combination with cell printing are exploited to generate hierarchical tissue-like structures. Materials that combine printability with cytocompatibility, so called bioinks, are currently the biggest bottleneck. Since recombinant spider silk proteins are non-immunogenic, cytocompatible, and exhibit physical crosslinking, their potential as a new bioink system was evaluated. Cell-loaded spider silk constructs can be printed by robotic dispensing without the need for crosslinking additives or thickeners for mechanical stabilization. Cells are able to adhere and proliferate with good viability over at least one week in such spider silk scaffolds. Introduction of a cell-binding motif to the spider silk protein further enables fine-tuned control over cell–material interactions. Spider silk hydrogels are thus a highly attractive novel bioink for biofabrication.
AUTHOR
Year
2
Journal/Proceedings
Angewandte Chemie International Edition
Reftype
DOI/URL
DOI
Groups
AbstractHydrogels are widely used in various biomedical applications, as they cannot only serve as materials for biofabrication but also as depots for the administration of drugs. However, the possibilities of formulation of water-insoluble drugs in hydrogels are rather limited. In this study, we assembled recombinant spider silk gels using a new processing route with aqueous-organic co-solvents, and the properties of these gels could be controlled by the choice of the co-solvent. The presence of the organic co-solvent further enabled the incorporation of hydrophobic drugs as exemplary shown for 6-mercaptopurine. The developed gels showed shear-thinning behaviour and could be easily injected to serve e.g. as drug depots and could even be 3D printed to serve as scaffolds for biofabrication. With this new processing route, the formulation of water-insoluble drugs in spider silk-based depots is possible, circumventing common pharmaceutical solubility issues.