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AUTHOR Kleger, Nicole and Cihova, Martina and Masania, Kunal and Studart, André R. and Löffler, Jörg F.
Title 3d printing of salt as a template for magnesium with structured porosity [Abstract]
Year 2019
Journal/Proceedings advanced materials
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Abstract Porosity is an essential feature in a wide range of applications that combine light weight with high surface area and tunable density. Porous materials can be easily prepared with a vast variety of chemistries using the salt-leaching technique. However, this templating approach has so far been limited to the fabrication of structures with random porosity and relatively simple macroscopic shapes. Here, a technique is reported that combines the ease of salt leaching with the complex shaping possibilities given by additive manufacturing (AM). By tuning the composition of surfactant and solvent, the salt-based paste is rheologically engineered and printed via direct ink writing into grid-like structures displaying structured pores that span from the sub-millimeter to the macroscopic scale. As a proof of concept, dried and sintered NaCl templates are infiltrated with magnesium (Mg), which is typically highly challenging to process by conventional AM techniques due to its highly oxidative nature and high vapor pressure. Mg scaffolds with well-controlled, ordered porosity are obtained after salt removal. The tunable mechanical properties and the potential to be predictably bioresorbed by the human body make these Mg scaffolds attractive for biomedical implants and demonstrate the great potential of this additive technique.
AUTHOR Kessel, Benjamin and Lee, Mihyun and Bonato, Angela and Tinguely, Yann and Tosoratti, Enrico and Zenobi-Wong, Marcy
Title 3D Bioprinting of Macroporous Materials Based on Entangled Hydrogel Microstrands [Abstract]
Year 2020
Journal/Proceedings Advanced Science
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Abstract Hydrogels are excellent mimetics of mammalian extracellular matrices and have found widespread use in tissue engineering. Nanoporosity of monolithic bulk hydrogels, however, limits mass transport of key biomolecules. Microgels used in 3D bioprinting achieve both custom shape and vastly improved permissivity to an array of cell functions, however spherical-microbead-based bioinks are challenging to upscale, are inherently isotropic, and require secondary crosslinking. Here, bioinks based on high-aspect-ratio hydrogel microstrands are introduced to overcome these limitations. Pre-crosslinked, bulk hydrogels are deconstructed into microstrands by sizing through a grid with apertures of 40–100 µm. The microstrands are moldable and form a porous, entangled structure, stable in aqueous medium without further crosslinking. Entangled microstrands have rheological properties characteristic of excellent bioinks for extrusion bioprinting. Furthermore, individual microstrands align during extrusion and facilitate the alignment of myotubes. Cells can be placed either inside or outside the hydrogel phase with >90% viability. Chondrocytes co-printed with the microstrands deposit abundant extracellular matrix, resulting in a modulus increase from 2.7 to 780.2 kPa after 6 weeks of culture. This powerful approach to deconstruct bulk hydrogels into advanced bioinks is both scalable and versatile, representing an important toolbox for 3D bioprinting of architected hydrogels.
AUTHOR Kokkinis, Dimitri and Bouville, Florian and Studart, André R.
Title 3D Printing of Materials with Tunable Failure via Bioinspired Mechanical Gradients [Abstract]
Year 2018
Journal/Proceedings Advanced Materials
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Abstract Mechanical gradients are useful to reduce strain mismatches in heterogeneous materials and thus prevent premature failure of devices in a wide range of applications. While complex graded designs are a hallmark of biological materials, gradients in manmade materials are often limited to 1D profiles due to the lack of adequate fabrication tools. Here, a multimaterial 3D‐printing platform is developed to fabricate elastomer gradients spanning three orders of magnitude in elastic modulus and used to investigate the role of various bioinspired gradient designs on the local and global mechanical behavior of synthetic materials. The digital image correlation data and finite element modeling indicate that gradients can be effectively used to manipulate the stress state and thus circumvent the weakening effect of defect‐rich interfaces or program the failure behavior of heterogeneous materials. Implementing this concept in materials with bioinspired designs can potentially lead to defect‐tolerant structures and to materials whose tunable failure facilitates repair of biomedical implants, stretchable electronics, or soft robotics.
AUTHOR Schaffner, Manuel and Faber, Jakob A. and Pianegonda, Lucas and Rühs, Patrick A. and Coulter, Fergal and Studart, André R.
Title 3D printing of robotic soft actuators with programmable bioinspired architectures [Abstract]
Year 2018
Journal/Proceedings Nature Communications
Reftype Schaffner2018
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Abstract
Soft actuation allows robots to interact safely with humans, other machines, and their surroundings. Full exploitation of the potential of soft actuators has, however, been hindered by the lack of simple manufacturing routes to generate multimaterial parts with intricate shapes and architectures. Here, we report a 3D printing platform for the seamless digital fabrication of pneumatic silicone actuators exhibiting programmable bioinspired architectures and motions. The actuators comprise an elastomeric body whose surface is decorated with reinforcing stripes at a well-defined lead angle. Similar to the fibrous architectures found in muscular hydrostats, the lead angle can be altered to achieve elongation, contraction, or twisting motions. Using a quantitative model based on lamination theory, we establish design principles for the digital fabrication of silicone-based soft actuators whose functional response is programmed within the material's properties and architecture. Exploring such programmability enables 3D printing of a broad range of soft morphing structures.
AUTHOR Schaffner, Manuel and R{"u}hs, Patrick A. and Coulter, Fergal and Kilcher, Samuel and Studart, Andr{'e} R.
Title 3D printing of bacteria into functional complex materials [Abstract]
Year 2017
Journal/Proceedings Science Advances
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Despite recent advances to control the spatial composition and dynamic functionalities of bacteria embedded in materials, bacterial localization into complex three-dimensional (3D) geometries remains a major challenge. We demonstrate a 3D printing approach to create bacteria-derived functional materials by combining the natural diverse metabolism of bacteria with the shape design freedom of additive manufacturing. To achieve this, we embedded bacteria in a biocompatible and functionalized 3D printing ink and printed two types of {textquotedblleft}living materials{textquotedblright} capable of degrading pollutants and of producing medically relevant bacterial cellulose. With this versatile bacteria-printing platform, complex materials displaying spatially specific compositions, geometry, and properties not accessed by standard technologies can be assembled from bottom up for new biotechnological and biomedical applications.
AUTHOR Fisch, Philipp and Broguiere, Nicolas and Finkielsztein, Sergio and Linder, Thomas and Zenobi-Wong, Marcy
Title Bioprinting of Cartilaginous Auricular Constructs Utilizing an Enzymatically Crosslinkable Bioink [Abstract]
Year 2021
Journal/Proceedings Advanced Functional Materials
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Abstract Bioprinting of functional tissues could overcome tissue shortages and allow a more rapid response for treatments. However, despite recent progress in bioprinting, and its outstanding ability to position cells and biomaterials in a precise 3D manner, its success has been limited, due to insufficient maturation of constructs into functional tissue. Here, a novel calcium-triggered enzymatic crosslinking (CTEC) mechanism for bioinks based on the activation cascade of Factor XIII is presented and utilized for the biofabrication of cartilaginous constructs. Hyaluronan transglutaminase (HA-TG), an enzymatically crosslinkable material, has shown excellent characteristics for chondrogenesis and builds the basis of the CTEC bioink. The bioink supports tissue maturation with neocartilage formation and stiffening of constructs up to 400 kPa. Bioprinted constructs remain stable in vivo for 24 weeks and bioprinted auricular constructs transform into cartilaginous grafts. A major limitation of the current study is the deposition of collagen I, indicating the maturation toward fibrocartilage rather than elastic cartilage. Shifting the maturation process toward elastic cartilage will therefore be essential in order for the developed bioinks to offer a novel tissue engineered treatment for microtia patients. CTEC bioprinting furthermore opens up use of enzymatically crosslinkable biopolymers and their modularity to support a multitude of tissues.
AUTHOR Müller, Michael and Fisch, Philipp and Molnar, Marc and Eggert, Sebastian and Binelli, Marco and Maniura-Weber, Katharina and Zenobi-Wong, Marcy
Title Development and thorough characterization of the processing steps of an ink for 3D printing for bone tissue engineering [Abstract]
Year 2020
Journal/Proceedings Materials Science and Engineering: C
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Achieving reproducibility in the 3D printing of biomaterials requires a robust polymer synthesis method to reduce batch-to-batch variation as well as methods to assure a thorough characterization throughout the manufacturing process. Particularly biomaterial inks containing large solid fractions such as ceramic particles, often required for bone tissue engineering applications, are prone to inhomogeneity originating from inadequate mixing or particle aggregation which can lead to inconsistent printing results. The production of such an ink for bone tissue engineering consisting of gellan gum methacrylate (GG-MA), hyaluronic acid methacrylate and hydroxyapatite (HAp) particles was therefore optimized in terms of GG-MA synthesis and ink preparation process, and the ink's printability was thoroughly characterized to assure homogeneous and reproducible printing results. A new buffer mediated synthesis method for GG-MA resulted in consistent degrees of substitution which allowed the creation of large 5 g batches. We found that both the new synthesis as well as cryomilling of the polymer components of the ink resulted in a decrease in viscosity from 113 kPa·s to 11.3 kPa·s at a shear rate of 0.1 s−1 but increased ink homogeneity. The ink homogeneity was assessed through thermogravimetric analysis and a newly developed extrusion force measurement setup. The ink displayed strong inter-layer adhesion between two printed ink layers as well as between a layer of ink with and a layer without HAp. The large polymer batch production along with the characterization of the ink during the manufacturing process allows ink production in the gram scale and could be used in applications such as the printing of osteochondral grafts.
AUTHOR Fisch, Philipp and Holub, Martin and Zenobi-Wong, Marcy
Title Improved accuracy and precision of bioprinting through progressive cavity pump-controlled extrusion [Abstract]
Year 2020
Journal/Proceedings bioRxiv
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3D bioprinting has seen a tremendous growth in recent years in a variety of fields such as tissue and organ models, drug testing and regenerative medicine. This growth has led researchers and manufacturers to continuously advance and develop novel bioprinting techniques and materials. Although new bioprinting methods are emerging (e.g. contactless and volumetric bioprinting), micro-extrusion bioprinting remains the most widely used method. Micro-extrusion bioprinting, however, is still largely dependent on the conventional pneumatic extrusion process, which relies heavily on homogenous biomaterial inks and bioinks to maintain a constant material flowrate. Augmenting the functionality of the bioink with the addition of nanoparticles, cells or biopolymers can induce inhomogeneities resulting in uneven material flow during printing and/or clogging of the nozzle, leading to defects in the printed construct. In this work, we evaluated a novel extrusion technique based on a miniaturized progressive cavity pump. We compared the accuracy and precision of this system to the pneumatic extrusion system and tested both for their effect on cell viability after extrusion. The progressive cavity pump achieved a significantly higher accuracy and precision compared to the pneumatic system while maintaining good viability and was able to maintain its reliability independently of the bioink composition, printing speed or nozzle size. Progressive cavity pumps are a promising tool for bioprinting and could help provide standardized and validated bioprinted constructs while leaving the researcher more freedom in the design of the bioinks with increased functionality.
AUTHOR Lee, Mihyun and Bae, Kraun and Levinson, Clara and Zenobi-Wong, Marcy
Title Nanocomposite bioink exploits dynamic covalent bonds between nanoparticles and polysaccharides for precision bioprinting [Abstract]
Year 2020
Journal/Proceedings Biofabrication
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The field of bioprinting has made significant recent progress towards engineering tissues with increasing complexity and functionality. It remains challenging, however, to develop bioinks with optimal biocompatibility and good printing fidelity. Here, we demonstrate enhanced printability of a polymer-based bioink based on dynamic covalent linkages between nanoparticles (NPs) and polymers, which retains good biocompatibility. Amine-presenting silica NPs (ca. 45 nm) were added to a polymeric ink containing oxidized alginate (OxA). The formation of reversible imine bonds between amines on the NPs and aldehydes of OxA lead to significantly improved rheological properties and high printing fidelity. In particular, the yield stress increased with increasing amounts of NPs (14.5 Pa without NPs, 79 Pa with 2 wt% NPs). In addition, the presence of dynamic covalent linkages in the gel provided improved mechanical stability over 7 d compared to ionically crosslinked gels. The nanocomposite ink retained high printability and mechanical strength, resulting in generation of centimeter-scale porous constructs and an ear structure with overhangs and high structural fidelity. Furthermore, the nanocomposite ink supported both in vitro and in vivo maturation of bioprinted gels containing chondrocytes. This approach based on simple oxidation can be applied to any polysaccharide, thus the widely applicability of the method is expected to advance the field towards the goal of precision bioprinting.
AUTHOR Alison, Lauriane and Menasce, Stefano and Bouville, Florian and Tervoort, Elena and Mattich, Iacopo and Ofner, Alessandro and Studart, André R.
Title 3D printing of sacrificial templates into hierarchical porous materials [Abstract]
Year 2019
Journal/Proceedings Scientific Reports
Reftype Alison2019
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Hierarchical porous materials are widespread in nature and find an increasing number of applications as catalytic supports, biological scaffolds and lightweight structures. Recent advances in additive manufacturing and 3D printing technologies have enabled the digital fabrication of porous materials in the form of lattices, cellular structures and foams across multiple length scales. However, current approaches do not allow for the fast manufacturing of bulk porous materials featuring pore sizes that span broadly from macroscopic dimensions down to the nanoscale. Here, ink formulations are designed and investigated to enable 3D printing of hierarchical materials displaying porosity at the nano-, micro- and macroscales. Pores are generated upon removal of nanodroplets and microscale templates present in the initial ink. Using particles to stabilize the droplet templates is key to obtain Pickering nanoemulsions that can be 3D printed through direct ink writing. The combination of such self-assembled templates with the spatial control offered by the printing process allows for the digital manufacturing of hierarchical materials exhibiting thus far inaccessible multiscale porosity and complex geometries.
AUTHOR Couck, Sarah and Saint-Remi, Julien Cousin and der Perre, Stijn Van and Baron, Gino V. and Minas, Clara and Ruch, Patrick and Denayer, Joeri F. M.
Title 3D-printed SAPO-34 monoliths for gas separation [Abstract]
Year 2018
Journal/Proceedings Microporous and Mesoporous Materials
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Abstract A 3D printing method (the Direct Ink writing, DIW, method) is applied to produce SAPO-34 zeolite based structured adsorbents with the shape of a honeycomb-like monolith. The use of the 3D printing technique gives this structure a well-defined and easily adaptable geometry. As binder material, methyl cellulose was used. The SAPO-34 monolith was characterized by SEM as well as Ar and Hg porosimetry. The CO2 adsorption affinity, capacity and heat of adsorption were determined by recording high pressure adsorption isotherms at different temperatures, using the gravimetric technique. The separation potential was investigated by means of breakthrough experiments with mixtures of CO2 and N2. The experimental selectivity of CO2/N2 separation was compared to the selectivity as predicted by the Ideal Adsorbed Solution Theory. A drop in capacity was noticed during the experiments and N2 capacities were close to zero or slightly negative due to the very low adsorption, meaning absolute selectivity values could not be determined. However, due to the low N2 capacity, experimental selectivity is estimated to be excellent as was predicted with IAST. While the 3D printing is found to be a practical, fast and flexible route to generate monolithic adsorbent structures, improvements in formulation are required in terms of sample robustness for handling purposes and heat transfer characteristics of the obtained monoliths during gas separation.
AUTHOR Lee, Mihyun and Bae, Kraun and Guillon, Pierre and Chang, Jin and Arlov, Øystein and Zenobi-Wong, Marcy
Title Exploitation of Cationic Silica Nanoparticles for Bioprinting of Large-Scale Constructs with High Printing Fidelity [Abstract]
Year 2018
Journal/Proceedings ACS Applied Materials and Interfaces
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Three-dimensional (3D) bioprinting allows the fabrication of 3D structures containing living cells whose 3D shape and architecture are matched to a patient. The feature is desirable to achieve personalized treatment of trauma or diseases. However, realization of this promising technique in the clinic is greatly hindered by inferior mechanical properties of most biocompatible bioink materials. Here, we report a novel strategy to achieve printing large constructs with high printing quality and fidelity using an extrusion-based printer. We incorporate cationic nanoparticles in an anionic polymer mixture, which significantly improves mechanical properties, printability, and printing fidelity of the polymeric bioink due to electrostatic interactions between the nanoparticles and polymers. Addition of cationic-modified silica nanoparticles to an anionic polymer mixture composed of alginate and gellan gum results in significantly increased zero-shear viscosity (1062%) as well as storage modulus (486%). As a result, it is possible to print a large (centimeter-scale) porous structure with high printing quality, whereas the use of the polymeric ink without the nanoparticles leads to collapse of the printed structure during printing. We demonstrate such a mechanical enhancement is achieved by adding nanoparticles within a certain size range (90%) and extracellular matrix secretion are observed for cells printed with nanocomposite inks. The design principle demonstrated can be applied for various anionic polymer-based systems, which could lead to achievement of 3D bioprinting-based personalized treatment.
AUTHOR Sommer, Marianne R. and Alison, Lauriane and Minas, Clara and Tervoort, Elena and Ruhs, Patrick A. and Studart, Andre R.
Title 3D printing of concentrated emulsions into multiphase biocompatible soft materials [Abstract]
Year 2017
Journal/Proceedings Soft Matter
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3D printing via direct ink writing (DIW) is a versatile additive manufacturing approach applicable to a variety of materials ranging from ceramics over composites to hydrogels. Due to the mild processing conditions compared to other additive manufacturing methods{,} DIW enables the incorporation of sensitive compounds such as proteins or drugs into the printed structure. Although emulsified oil-in-water systems are commonly used vehicles for such compounds in biomedical{,} pharmaceutical{,} and cosmetic applications{,} printing of such emulsions into architectured soft materials has not been fully exploited and would open new possibilities for the controlled delivery of sensitive compounds. Here{,} we 3D print concentrated emulsions into soft materials{,} whose multiphase architecture allows for site-specific incorporation of both hydrophobic and hydrophilic compounds into the same structure. As a model ink{,} concentrated emulsions stabilized by chitosan-modified silica nanoparticles are studied{,} because they are sufficiently stable against coalescence during the centrifugation step needed to create a bridging network of droplets. The resulting ink is ideal for 3D printing as it displays high yield stress{,} storage modulus and elastic recovery{,} through the formation of networks of droplets as well as of gelled silica nanoparticles in the presence of chitosan. To demonstrate possible architectures{,} we print biocompatible soft materials with tunable hierarchical porosity containing an encapsulated hydrophobic compound positioned in specific locations of the structure. The proposed emulsion-based ink system offers great flexibility in terms of 3D shaping and local compositional control{,} and can potentially help address current challenges involving the delivery of incompatible compounds in biomedical applications.
AUTHOR Siqueira, Gilberto and Kokkinis, Dimitri and Libanori, Rafael and Hausmann, Michael K. and Gladman, Amelia Sydney and Neels, Antonia and Tingaut, Philippe and Zimmermann, Tanja and Lewis, Jennifer A. and Studart, André R.
Title Cellulose Nanocrystal Inks for 3D Printing of Textured Cellular Architectures [Abstract]
Year 2017
Journal/Proceedings Advanced Functional Materials
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3D printing of renewable building blocks like cellulose nanocrystals offers an attractive pathway for fabricating sustainable structures. Here, viscoelastic inks composed of anisotropic cellulose nanocrystals (CNC) that enable patterning of 3D objects by direct ink writing are designed and formulated. These concentrated inks are composed of CNC particles suspended in either water or a photopolymerizable monomer solution. The shear-induced alignment of these anisotropic building blocks during printing is quantified by atomic force microscopy, polarized light microscopy, and 2D wide-angle X-ray scattering measurements. Akin to the microreinforcing effect in plant cell walls, the alignment of CNC particles during direct writing yields textured composites with enhanced stiffness along the printing direction. The observations serve as an important step forward toward the development of sustainable materials for 3D printing of cellular architectures with tailored mechanical properties.
AUTHOR Minas, Clara and Carnelli, Davide and Tervoort, Elena and Studart, André R.
Title 3D Printing of Emulsions and Foams into Hierarchical Porous Ceramics [Abstract]
Year 2016
Journal/Proceedings Advanced Materials
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Bulk hierarchical porous ceramics with unprecedented strength-to-weight ratio and tunable pore sizes across three different length scales are printed by direct ink writing. Such an extrusion-based process relies on the formulation of inks in the form of particle-stabilized emulsions and foams that are sufficiently stable to resist coalescence during printing.
AUTHOR Sommer, Marianne R. and Schaffner, Manuel and Carnelli, Davide and Studart, André R.
Title 3D Printing of Hierarchical Silk Fibroin Structures [Abstract]
Year 2016
Journal/Proceedings ACS Applied Materials and Interfaces
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Like many other natural materials, silk is hierarchically structured from the amino acid level up to the cocoon or spider web macroscopic structures. Despite being used industrially in a number of applications, hierarchically structured silk fibroin objects with a similar degree of architectural control as in natural structures have not been produced yet due to limitations in fabrication processes. In a combined top-down and bottom-up approach, we exploit the freedom in macroscopic design offered by 3D printing and the template-guided assembly of ink building blocks at the meso- and nanolevel to fabricate hierarchical silk porous materials with unprecedented structural control. Pores with tunable sizes in the range 40–350 μm are generated by adding sacrificial organic microparticles as templates to a silk fibroin-based ink. Commercially available wax particles or monodisperse polycaprolactone made by microfluidics can be used as microparticle templates. Since closed pores are generated after template removal, an ultrasonication treatment can optionally be used to achieve open porosity. Such pore templating particles can be further modified with nanoparticles to create a hierarchical template that results in porous structures with a defined nanotopography on the pore walls. The hierarchically porous silk structures obtained with this processing technique can potentially be utilized in various application fields from structural materials to thermal insulation to tissue engineering scaffolds.
AUTHOR M{"u}ller, Michael and {"O}zt{"u}rk, Ece and Arlov, {O}ystein and Gatenholm, Paul and Zenobi-Wong, Marcy
Title Alginate Sulfate--Nanocellulose Bioinks for Cartilage Bioprinting Applications [Abstract]
Year 2016
Journal/Proceedings Annals of Biomedical Engineering
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One of the challenges of bioprinting is to identify bioinks which support cell growth, tissue maturation, and ultimately the formation of functional grafts for use in regenerative medicine. The influence of this new biofabrication technology on biology of living cells, however, is still being evaluated. Recently we have identified a mitogenic hydrogel system based on alginate sulfate which potently supports chondrocyte phenotype, but is not printable due to its rheological properties (no yield point). To convert alginate sulfate to a printable bioink, it was combined with nanocellulose, which has been shown to possess very good printability. The alginate sulfate/nanocellulose ink showed good printing properties and the non-printed bioink material promoted cell spreading, proliferation, and collagen II synthesis by the encapsulated cells. When the bioink was printed, the biological performance of the cells was highly dependent on the nozzle geometry. Cell spreading properties were maintained with the lowest extrusion pressure and shear stress. However, extruding the alginate sulfate/nanocellulose bioink and chondrocytes significantly compromised cell proliferation, particularly when using small diameter nozzles and valves.
AUTHOR Kesti, Matti and Fisch, Philipp and Pensalfini, Marco and Mazza, Edoardo and Zenobi-Wong, Marcy
Title Guidelines for standardization of bioprinting: a systematic study of process parameters and their effect on bioprinted structures [Abstract]
Year 2016
Journal/Proceedings BioNanoMaterials
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Biofabrication techniques including three-dimensional bioprinting could be used one day to fabricate living, patient-specific tissues and organs for use in regenerative medicine. Compared to traditional casting and molding methods, bioprinted structures can be much more complex, containing for example multiple materials and cell types in controlled spatial arrangement, engineered porosity, reinforcement structures and gradients in mechanical properties. With this complexity and increased function, however, comes the necessity to develop guidelines to standardize the bioprinting process, so printed grafts can safely enter the clinics. The bioink material must firstly fulfil requirements for biocompatibility and flow. Secondly, it is important to understand how process parameters affect the final mechanical properties of the printed graft. Using a gellan-alginate physically crosslinked bioink as an example, we show shear thinning and shear recovery properties which allow good printing resolution. Printed tensile specimens were used to systematically assess effect of line spacing, printing direction and crosslinking conditions. This standardized testing allowed direct comparison between this bioink and three commercially-available products. Bioprinting is a promising, yet complex fabrication method whose outcome is sensitive to a range of process parameters. This study provides the foundation for highly needed best practice guidelines for reproducible and safe bioprinted grafts.
AUTHOR Kesti, Matti and Eberhardt, Christian and Pagliccia, Guglielmo and Kenkel, David and Grande, Daniel and Boss, Andreas and Zenobi-Wong, Marcy
Title Bioprinting Complex Cartilaginous Structures with Clinically Compliant Biomaterials [Abstract]
Year 2015
Journal/Proceedings Advanced Functional Materials
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Bioprinting is an emerging technology for the fabrication of patient-specific, anatomically complex tissues and organs. A novel bioink for printing cartilage grafts is developed based on two unmodified FDA-compliant polysaccharides, gellan and alginate, combined with the clinical product BioCartilage (cartilage extracellular matrix particles). Cell-friendly physical gelation of the bioink occurs in the presence of cations, which are delivered by co-extrusion of a cation-loaded transient support polymer to stabilize overhanging structures. Rheological properties of the bioink reveal optimal shear thinning and shear recovery properties for high-fidelity bioprinting. Tensile testing of the bioprinted grafts reveals a strong, ductile material. As proof of concept, 3D auricular, nasal, meniscal, and vertebral disk grafts are printed based on computer tomography data or generic 3D models. Grafts after 8 weeks in vitro are scanned using magnetic resonance imaging and histological evaluation is performed. The bioink containing BioCartilage supports proliferation of chondrocytes and, in the presence of transforming growth factor beta-3, supports strong deposition of cartilage matrix proteins. A clinically compliant bioprinting method is presented which yields patient-specific cartilage grafts with good mechanical and biological properties. The versatile method can be used with any type of tissue particles to create tissue-specific and bioactive scaffolds.
AUTHOR M{"{u}}ller, Michael and Becher, Jana and Schnabelrauch, Matthias and Zenobi-Wong, Marcy
Title Nanostructured Pluronic hydrogels as bioinks for 3D bioprinting [Abstract]
Year 2015
Journal/Proceedings Biofabrication
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Bioprinting is an emerging technology in the field of tissue engineering as it allows the precise positioning of biologically relevant materials in 3D, which more resembles the native tissue in our body than current homogenous, bulk approaches. There is however a lack of materials to be used with this technology and materials such as the block copolymer Pluronic have good printing properties but do not allow long-term cell culture. Here we present an approach called nanostructuring to increase the biocompatibility of Pluronic gels at printable concentrations. By mixing acrylated with unmodified Pluronic F127 it was possible to maintain the excellent printing properties of Pluronic and to create stable gels via UV crosslinking. By subsequent elution of the unmodified Pluronic from the crosslinked network we were able to increase the cell viability of encapsulated chondrocytes at day 14 from 62% for a pure acrylated Pluronic hydrogel to 86% for a nanostructured hydrogel. The mixed Pluronic gels also showed good printability when cells where included in the bioink. The nanostructured gels were, with a compressive modulus of 1.42 kPa, mechanically weak, but we were able to increase the mechanical properties by the addition of methacrylated hyaluronic acid. Our nanostructuring approach enables Pluronic hydrogels to have the desired set of properties in all stages of the bioprinting process.
AUTHOR Kesti, Matti and M{"{u}}ller, Michael and Becher, Jana and Schnabelrauch, Matthias and D{textquoteright}Este, Matteo and Eglin, David and Zenobi-Wong, Marcy
Title A versatile bioink for three-dimensional printing of cellular scaffolds based on thermally and photo-triggered tandem gelation [Abstract]
Year 2014
Journal/Proceedings Acta Biomaterialia
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Abstract Layer-by-layer bioprinting is a logical choice for the fabrication of stratified tissues like articular cartilage. Printing of viable organ replacements, however, is dependent on bioinks with appropriate rheological and cytocompatible properties. In cartilage engineering, photocrosslinkable glycosaminoglycan-based hydrogels are chondrogenic, but alone have generally poor printing properties. By blending the thermoresponsive polymer poly(N-isopropylacrylamide) grafted hyaluronan (HA-pNIPAAM) with methacrylated hyaluronan (HAMA), high-resolution scaffolds with good viability were printed. HA-pNIPAAM provided fast gelation and immediate post-printing structural fidelity, while {HAMA} ensured long-term mechanical stability upon photocrosslinking. The bioink was evaluated for rheological properties, swelling behavior, printability and biocompatibility of encapsulated bovine chondrocytes. Elution of HA-pNIPAAM from the scaffold was necessary to obtain good viability. HA-pNIPAAM can therefore be used to support extrusion of a range of biopolymers which undergo tandem gelation, thereby facilitating the printing of cell-laden, stratified cartilage constructs with zonally varying composition and stiffness.
AUTHOR M{"{u}}ller, Michael and Becher, Jana and Schnabelrauch, Matthias and Zenobi-Wong, Marcy
Title Printing thermoresponsive reverse molds for the creation of patterned two-component hydrogels for 3D cell culture. [Abstract]
Year 2013
Journal/Proceedings Journal of visualized experiments : JoVE
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Bioprinting is an emerging technology that has its origins in the rapid prototyping industry. The different printing processes can be divided into contact bioprinting(1-4) (extrusion, dip pen and soft lithography), contactless bioprinting(5-7) (laser forward transfer, ink-jet deposition) and laser based techniques such as two photon photopolymerization(8). It can be used for many applications such as tissue engineering(9-13), biosensor microfabrication(14-16) and as a tool to answer basic biological questions such as influences of co-culturing of different cell types(17). Unlike common photolithographic or soft-lithographic methods, extrusion bioprinting has the advantage that it does not require a separate mask or stamp. Using CAD software, the design of the structure can quickly be changed and adjusted according to the requirements of the operator. This makes bioprinting more flexible than lithography-based approaches. Here we demonstrate the printing of a sacrificial mold to create a multi-material 3D structure using an array of pillars within a hydrogel as an example. These pillars could represent hollow structures for a vascular network or the tubes within a nerve guide conduit. The material chosen for the sacrificial mold was poloxamer 407, a thermoresponsive polymer with excellent printing properties which is liquid at 4 degrees C and a solid above its gelation temperature ~20 degrees C for 24.5% w/v solutions(18). This property allows the poloxamer-based sacrificial mold to be eluted on demand and has advantages over the slow dissolution of a solid material especially for narrow geometries. Poloxamer was printed on microscope glass slides to create the sacrificial mold. Agarose was pipetted into the mold and cooled until gelation. After elution of the poloxamer in ice cold water, the voids in the agarose mold were filled with alginate methacrylate spiked with FITC labeled fibrinogen. The filled voids were then cross-linked with UV and the construct was imaged with an epi-fluorescence microscope.