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A new approach that offers the potential for local drug delivery to the inner ear is a 3D printed, patient individualized, drug-loaded implant that precisely fits into the round window niche (RWN). Anatomically correct digital light processing (DLP) 3D printed implant prototypes are beneficial for preoperative planning and rehearsal of implantation techniques due to tactile feedback. The aim is to define desired mechanical material properties for future RWN implants. For this purpose, RWN implant prototypes (RWN-IPs) were DLP 3D printed using commercially available E-Shell 500 and E-Shell 600 materials (Envisiontec GmbH, Gladbeck, Germany) and a selfestablished PEGDA700 composition. These photopolymers are suitable for 3D printing RWN-IPs that feature different mechanical characteristics. The (1) mechanical properties (tensile test) were investigated, (2) the implantation feasibility and (3) fitting accuracy in human cadaver RWN were evaluated. As a result, E-Shell 500 has relatively high stretchability (ɛm ~ 60%) while E-Shell 600 and PEGDA700 are brittle and PEGDA700 has low strength. The E-Shell 500 material performs by far the best at handling and insertion. EShell 600 has adequate strength but is hard to handle because of rigid material behavior. PEGDA700 enables high 3D printing accuracy but lacks adequate mechanical behavior for adequate insertion of implant prototypes in RWN.

Hydrogels are 3D polymeric networks, which exhibit properties such as softness, viscoelasticity and their ability to absorb large amounts of water. These characteristics make them exceptionally suitable in biomedicine as e.g. tissue scaffolds, drug delivery systems, wound dressings or contact lenses. One of these hydrogels is the biocompatible, hydrophilic and photopolymerizable poly(ethylene glycol) diacrylate (PEGDA). It is used in different biomedical applications due to its tunable mechanical characteristics. In our study, the mechanical properties of different PEGDA hydrogel compositions with variyng molecular masses and contents of water/methanol, were investigated. Different compositions containing 20 m%, 30 m% or 40 m% of PEGDA4K(4,000 g/mol), PEGDA10K(10,000 g/mol) or PEGDA20K(20,000 g/mol) in ultrapure water/methanol (1:2) were produced. Dumbbell-shaped samples were prepared in molds via photopolymerization in a UV chamber. Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) was used as photoinitiator (0.5% w/w). The mechanical testing was performed using a uniaxial testing system. The obtained results showed averagely 78% higher tensile strength (σmax) values for 30 m% and 40 m% samples in comparison with 20 m% samples for all of the tested polymers. PEGDA20K30 m% samples showed the highest σmax among all of the samples with 12.8 MPa. All of the PEGDA20K samples exhibited the highest elongation at break (εB) values (up to 958%), whereas the lowest values were found for PEGDA4K(up to 105%). The obtained stress-strain curves for most of the samples were typical for deformable, amorphous polymers with a deformation upon reaching a critical stress point. The PEGDA materials showed variable mechanical characteristics according to changing molecular mass or polymer concentration. These promising results showed that it should be possible to compose scaffolds with desired mechanical stability according to the needed application.

A novel approach for the long-term medical treatment of the inner ear is the diffusion of drugs through the round window membrane from a patient-individualized, drug-eluting implant, which is inserted in the middle ear. In this study, drug-loaded (10 wt% Dexamethasone) guinea pig round window niche implants (GP-RNIs, ~1.30 mm × 0.95 mm × 0.60 mm) were manufactured with high precision via micro injection molding (µIM, Tmold = 160 °C, crosslinking time of 120 s). Each implant has a handle (~3.00 mm × 1.00 mm × 0.30 mm) that can be used to hold the implant. A medical-grade silicone elastomer was used as implant material. Molds for µIM were 3D printed from a commercially available resin (TG = 84 °C) via a high-resolution DLP process (xy resolution of 32 µm, z resolution of 10 µm, 3D printing time of about 6 h). Drug release, biocompatibility, and bioefficacy of the GP-RNIs were investigated in vitro. GP-RNIs could be successfully produced. The wear of the molds due to thermal stress was observed. However, the molds are suitable for single use in the µIM process. About 10% of the drug load (8.2 ± 0.6 µg) was released after 6 weeks (medium: isotonic saline). The implants showed high biocompatibility over 28 days (lowest cell viability ~80%). Moreover, we found anti-inflammatory effects over 28 days in a TNF-α-reduction test. These results are promising for the development of long-term drug-releasing implants for human inner ear therapy.

Novel 3D printing techniques enable the development of medical devices with drug delivery systems that are tailored to the patient in terms of scaffold shape and the desired pharmaceutically active substance release. Gentle curing methods such as photopolymerization are also relevant for the incorporation of potent and sensitive drugs including proteins. However, retaining the pharmaceutical functions of proteins remains challenging due to the possible crosslinking between the functional groups of proteins, and the used photopolymers such as acrylates. In this work, the in vitro release of the model protein drug, albumin–fluorescein isothiocyanate conjugate (BSA–FITC) from differently composed, photopolymerized poly(ethylene) glycol diacrylate (PEGDA), an often employed, nontoxic, easily curable resin, was investigated. Different PEGDA concentrations in water (20, 30, and 40 wt %) and their different molecular masses (4000, 10,000, and 20,000 g/mol) were used to prepare a protein carrier with photopolymerization and molding. The viscosity measurements of photomonomer solutions revealed exponentially increasing values with increasing PEGDA concentration and molecular mass. Polymerized samples showed increasing medium uptake with an increasing molecular mass and decreasing uptake with increasing PEGDA content. Therefore, the modification of the inner network resulted in the most swollen samples (20 wt %) also releasing the highest amount of incorporated BSA–FITC for all PEGDA molecular masses.

Purpose The extension of the vacuum-assisted multipoint moulding (VAMM) technology to a broader field of geometries makes it necessary to extend it with attachments to the enhanced vacuum-assisted multipoint moulding with additive attachments (EMMA) technology. Therefore, it is necessary to build additive manufactured attachments on a curved silicone surface by fused filament fabrication (FFF). The main challenge of FFF on a silicone-made build plate is the adhesion of the part on the build plate. Hence, the purpose of this paper is to find suitable and reliably manufacturable material and adhesion promoter combinations for the use of the FFF on silicone build plates. Design/methodology/approach The combinations of seven different filaments and four adhesion promoters were investigated with an experimental study. Therefore, four different specimen geometries were built with the different combinations and tested in a tensile test, and some of the specimens were analysed with a confocal laser scanning microscope (CLSM). Findings This study proves that the FFF on unheated silicone building plates is possible for several material combinations. As a filament material, polylactide can reliably be manufactured with all of the investigated adhesion promoters on the silicone build plate. Thereby, the highest adhesion strengths were achieved with an adhesive foil as an adhesion promoter, whereas the glue stick is the most appropriate solution. The investigations with the CLSM showed that there are large differences in the manifestation of the first layer depending on the adhesion promoter used. Originality/value To the best of the authors’ knowledge, this study is the first to demonstrate the manufacturing of FFF-made attachments on silicone build plates for the EMMA process. This paper provides measurement data on the build plate adhesion of the attachments on silicone-made build plates.

The culverts are used to safely convey water under railways, highways, and overpasses. They are utilized in drainage areas or water channels and in areas where the bearing capacity of soil is low. The design and construction of this crucial infrastructure need to be improved to meet contemporary demands of reliability and affordability. Precast reinforced box culverts are popular alternatives as they ensure strength, durability, rigidity, and economy. This research seeks to develop an effective and affordable design improvement procedure for a precast box culvert using modern numerical tools. The Finite Element Method (FEM) based approach is used in studying the effects of haunch geometry and additional steel reinforcement on the load-bearing capacity of box culverts. A conventional box culvert is analyzed to create the numerical models in the Abaqus FEM code and to investigate the load-bearing capacity of culverts with an expanded span. The outcomes of the study reveal the critical places for stress concentration as well as the location of maximum damage. It is found that haunch geometry and additional reinforcement at these critical places significantly affect the load-carrying capacity of a culvert. From the comparison of capacity curves of models with and without haunches and diagonal reinforcement, it is found that a 25% increase in load-carrying capacity is achievable with the recommended changes. The proposed design improvement technique can be employed for the cost-effective and safe design of a concrete box culvert with larger span lengths and high water-flowing capacities. The findings of this study are expected to assist practitioners in strength enhancement tasks of box culverts for increased structural stability and drainage efficiency.

Here, we demonstrate a manufacturing process for individualised, small-sized implant prototypes. Our process is promising for the manufacturing of drug-releasing (micro)implants to be implanted in the round window niche (RWN-I, solid body, free-form-shaped design, 1.1 x 2.7 x 3.1 mm) and for frontal neo-ostium implants (FO-I, tube-like design, length ~ 7 mm, Ø ~ 2-6 mm) for frontal sinus drainage. Implant prototypes are manufactured using micro injection molding (μIM). We use digital light processing (DLP) as a 3D printing technique for rapid tooling of accurate molds for the μIM process. A common acrylate-based photopolymer for stiff and high-detailed modelling but with low head deflection temperature of HDT = 60.5 °C is used for DLP 3D printing of the molds. The molds were 3D printed with a layer height of 50 μm in about 20 min (RWN-I) and 60 min (FO-I). For μIM investigations, we use liquid silicone rubber (LSR) as a biocompatible and medically relevant material. Micro injection molding of LSR was investigated using mold temperatures between Tmold = 110 °C (long tcuring ~ 2 h) up to Tmold = 160 °C (short tcuring ~ 5 min). As a result, small-sized, complex-shaped implant prototypes of LSR can be successfully manufactured via μIM using high Tmold = 160 °C and short curing time. DLP 3D printing material with relative low HDT = 60.5 °C was suitable for μIM. There is no significant wear of the molds, when used for a low number of μIM cycles (n ~ 8). Design of metal mold housing has to be suitable (perfect fit of mold, no cavities facing the molds surface for prevention of thermal expansion of mold into cavities).

Drug delivery systems (DDS) are suitable for controlled local drug release in order to ensure safety and effectiveness of medical treatment. The choice and characterization of biomaterials that can be used as a DDS is a challenging step in the administration of drugs. Novel 3D printing photopolymerization-based techniques create the possibility for designing individual, patient-tailored DDS. Poly(ethylene glycol) diacrylate`s (PEGDA`s) chemical and biological properties make it a suitable photopolymerisable resin for the creation of DDS. This study describes the in vitro release of the antiseptic drug chlorhexidine (CHX) from UV-cured PEGDA and its copolymers (butanediol diacrylate, pentaerythritol triacrylate and pentaerythritol tetraacrylate) samples. A substantial decrease in CHX release with increasing concentration of the copolymers in comparison to pure PEGDA was obtained only for butanediol diacrylate. For pentaerythritol triacrylate and pentaerythritol tetraacrylate only a tendency of decreased CHX release with increasing concentration was detected. Therefore, release profiles of the low molecular drug CHX from PEGDA samples could be modified by the addition of copolymers with a different number of acrylate groups and PEGDA can be considered as a promising candidate for the preparation of novel DDS.

Micro-electrode array (MEA) systems are noninvasive platforms for the investigation of electrophysiological properties of cell layers, such as spontaneously active cardiomyocytes. An MEA chip is composed of two-dimensional grids of dot-like electrodes embedded into glass. Here we present a test setup featuring a customised two-chamber silicone overlay. The overlay is designed to be placed on an MEA with two separate electrode fields and enables the seeding of two distinct cell sub-types on the MEA for synchronised drug testing applications while giving the possibility of analysing intersubtype-specific cellular interactions. The overlay has a full size of 10 x 10 x 5 mm (width x length x height), each chamber has a size of 2.5 x 6 x 5 mm (V = 75 mm³). The chambers are separated by a wall with a thickness of 0.3 mm. The overlay was manufactured via silicone-casting, utilising a 3D printed model. The model is 3D printed via high accurate digital light processing (DLP). In addition, a DLP 3D printed cover optimises the attachment of the overlay on an MEA. A proofof- principle of the utilisation of the overlay is demonstrated.

Enhanced multipoint moulding with additive attachments (EMMA) is a process combining vacuum-assisted multipoint moulding (VAMM) and additively manufactured moulding attachments for carbon fibre reinforced plastics (CFRP) component production. The aim of this initial study is to investigate the mouldability of the additively manufactured attachments on the multipoint tool. For this purpose, two different test specimens were defined, the VAMM machine was adjusted, the attachments were additively built with the robot on the curved silicone interpolation layer and lastly, the CFRP specimens were moulded. The fabrication results were analysed with surface comparisons to check that there was no displacement of the attachments during moulding. A visual evaluation of the manufactured components was carried out, and the overall dimensional accuracy was assessed by comparing the surface with the target geometry. The results showed a very good agreement between the shapes before and after the moulding and thus prove that the attachments were not postponed in the moulding process. The optical evaluation confirms good moulding results for the parts manufactured with the enhanced multipoint moulding with additive attachments. Moreover, the evaluation shows that the major parts of the specimens comply with the permissible tolerance of t = 6 mm defined in ISO 20457. To the authors’ best knowledge, this is the first study that has investigated the entire EMMA process and systematically proved the mouldability of the additively manufactured attachments on multipoint tools.

Lateral adhesion forces are a fundamental property of liquid-solid interactions and a key aspect of dynamic droplet mobility. But, commonly applied conventional wetting analysis is limited to static and quasi-static methods and cannot resolve dynamic and spatial liquid-solid interactions. However, droplet mobility is assumed to be affected by chemical and topographic surface inhomogeneities introduced by femtosecond laser treatment.In this study, we used a customized droplet adhesion force instrument to determine lateral adhesion forces on various femtosecond laser-structured surface designs to obtain a deeper understanding of the dynamic droplet motion with regard to chemical and topographic surface features.We show that the droplet motion was highly affected by the chemical and topographical surface design and local inhomogeneities. The droplet mobility on femtosecond laser-structured surfaces could be classified into a static, a transfer, and a kinetic regime, which is essential for designing surfaces with extreme wetting characteristics and a wide range of scientific and industrial processes. Furthermore, with proper tailoring of surface structures and chemical modification, we were able to provoke adhesion forces on self-organized laser microstructures similar to those found on the natural lotus leaves.

A method of mathematical modeling of the ordered surface relief of titanium alloy Ti6Al4V after femtosecond laser treatment is proposed, which allowed obtaining the informative signs of the self-organized surface irregularities, taking into account the stochastic and cyclic nature of this process. An algorithm has been developed, and a package of computer programshas been created based on the proposed mathematical model. These methods make it possible to analyze the zone-spatial two-dimensional structure of the cyclic relief of the modified surface. They are also the basis for creating the specialized software forthe automated profilometric diagnostic systems.

Three-dimensional (3D) printing technology enables the design of personalized scaffolds with tunable pore size and composition. Combining decellularization and 3D printing techniques provides the opportunity to fabricate scaffolds with high potential to mimic native tissue. The aim of this study is to produce novel decellularized bone extracellular matrix (dbECM)-reinforced composite-scaffold that can be used as a biomaterial for bone tissue engineering. Decellularized bone particles (dbPTs, ∼100 ​μm diameter) were obtained from rabbit femur and used as a reinforcement agent by mixing with gelatin (GEL) in different concentrations. 3D scaffolds were fabricated by using an extrusion-based bioprinter and crosslinking with microbial transglutaminase (mTG) enzyme, followed by freeze-drying to obtain porous structures. Fabricated 3D scaffolds were characterized morphologically, mechanically, and chemically. Furthermore, MC3T3-E1 mouse pre-osteoblast cells were seeded on the dbPTs reinforced GEL scaffolds (GEL/dbPTs) and cultured for 21 days to assess cytocompatibility and cell attachment. We demonstrate the 3D-printability of dbPTs-reinforced GEL hydrogels and the achievement of homogenous distribution of the dbPTs in the whole scaffold structure, as well as bioactivity and cytocompatibility of GEL/dbPTs scaffolds. It was shown that Young's modulus and degradation rate of scaffolds were enhanced with increasing dbPTs content. Multiphoton microscopy imaging displayed the interaction of cells with dbPTs, indicating attachment and proliferation of cells around the particles as well as into the GEL-particle hydrogels. Our results demonstrate that GEL/dbPTs hydrogel formulations have potential for bone tissue engineering.

To use regeneratively active cells for cell therapeutic applications, the cells must be isolated from their resident tissues. Different isolation procedures subject these cells to varying degrees of mechanical strain, which can affect the yield of cell number and viability. Knowledge of cell volumetric mass density is important for experimental and numerical optimization of these procedures. Although methods for measuring cell volumetric mass density already exist, they either consume much time and cell material or require a special setup. Therefore, we developed a user-friendly method that is based on the use of readily available instrumentation. The newly developed method is predicated on the linear relationship between the volumetric mass density of the cell suspension and the volumetric mass density, number, and diameter of the cells in the suspension. We used this method to determine the volumetric mass density of mesenchymal stem cells (MSCs) and compared it to results from the established density centrifugation.

Novel fabrication techniques based on photopolymerization enable the preparation of complex multi-material constructs for biomedical applications. This requires an understanding of the influence of the used reaction components on the properties of the generated copolymers. The identification of fundamental characteristics of these copolymers is necessary to evaluate their potential for biomaterial applications. Additionally, knowledge of the properties of the starting materials enables subsequent tailoring of the biomaterials to meet individual implantation needs. In our study, we have analyzed the biological, chemical, mechanical and thermal properties of photopolymerized poly(ethyleneglycol) diacrylate (PEGDA) and specific copolymers with different photoinitiator (PI) concentrations before and after applying a post treatment washing process. As comonomers, 1,3-butanediol diacrylate, pentaerythritol triacrylate and pentaerythritol tetraacrylate were used. The in vitro studies confirm the biocompatibility of all investigated copolymers. Uniaxial tensile tests show significantly lower tensile strength (82% decrease) and elongation at break (76% decrease) values for washed samples. Altered tensile strength is also observed for different PI concentrations: on average, 6.2 MPa for 1.25% PI and 3.1 MPa for 0.5% PI. The addition of comonomers lowers elongation at break on average by 45%. Moreover, our observations show glass transition temperatures (Tg) ranging from 27 °C to 56 °C, which significantly increase with higher comonomer content. These results confirm the ability to generate biocompatible PEGDA copolymers with specific thermal and mechanical properties. These can be considered as resins for various additive manufacturing-based applications to obtain personalized medical devices, such as drug delivery systems (DDS). Therefore, our study has advanced the understanding of PEGDA multi-materials and will contribute to the future development of tools ensuring safe and effective individual therapy for patients.

Photopolymerizing, high-resolution 3D printing methods such as Stereolithography (SLA) or Digital Light Processing (DLP) are very promising for the manufacturing of drug-incorporated, patient specific implants. However, a drug-load may be limited by adequately solubility of the active pharmaceutical ingredient (API) in the photopolymer. Furthermore, a drug-load may affect the mechanical properties of the material negatively. Here, we investigate the DLP 3D printing of drugincorporated photopolymers. Polyethylene glycol diacrylate (PEGDA, Mn = 700 g/mol) is used as matrix polymer and Dexamethasone (DEX) is used for drug-loading (10 g/L and 20 g/L). Compressive properties, drug release and drug stability of 3D printed test samples were analyzed. DEX was found to be sparingly soluble in the PEGDA-based photopolymer. Not all drug particles can be dissolved at a concentration of 20 g/L and a slurry-like suspension is formed. Drug-incorporated photopolymers of 10 g/L (solution) and 20 g/L (suspension) were processed successfully via DLP. The higher the drug-load, the lower the compressive strength. Mechanical properties can be improved via a post-curing in a UV light curing box. Drug-incorporated 3D printed test samples show burst-release of DEX. The post-curing process does not affect drug release. DEX degrades in 3D-printed test samples significantly (~ 30 %) over a several days time period.

Vascularization of bioprinted constructs to ensure sufficient nutrient supply still remains to be a significant task in the tissue engineering community. In order to mimic functional tissue, it is necessary to be able to print vessels in various size scales, which places particularly high demands on the 3D printing technology and materials. In this preliminary study, we focused on the production of small hollow structures for the application in small functional units of living tissue. To fabricate hollow structures, the freeform reversible embedding of suspended hydrogels (FRESH) - method was utilized (Hinton et al.). A sodium alginate solution (5 % w/v) was used as a bioink. The scaffolds were fabricated with the Allevi 1 (Allevi Inc., PA, USA), a pneumatic extrusion-based bioprinter and plotted into a gelatine slurry serving as fugitive support. For first cell experiments, the bioink was loaded with immortalized mouse HL1-cells. A proof of concept could be shown since we were able to reliably create vessel-like structures with an inside diameter of 1.2 to 1.6 mm, a length of up to 8 mm and a wall thickness of 0.4 to 0.6 mm. In this study, the geometric requirements to print hollow structures for small functional tissues could be achieved. To expand the field of applications the resolution of the printing process has to be further improved. Moreover, the cell density should be increased to reach physiological cell numbers and extended with endothelial cells.

Hydrostatic high-pressure technology (HHD) devitalizes tissue quickly and gently, without negatively affecting the structural properties. HHD-treated tissues must be cleaned from devitalized cells. A partially automated, gentle, reproducible and timesaving rinsing test setup utilizing ultrasound is demonstrated in this study. The test setup is used to clean HHD-treated bone allografts of tissue residues and prevent microbiological contamination. A rinsing procedure is investigated. Residual DNA content determination is utilized to analyze cleaned bone allograft tissue for rinsing procedure evaluation.

Novel fabrication techniques based on photopolymerization enable the preparation of complex multi-material constructs for biomedical applications. This requires an understanding of the influence of the used reaction components on the properties of the generated copolymers. The identification of fundamental characteristics of these copolymers is necessary to evaluate their potential for biomaterial applications. Additionally, knowledge of the properties of the starting materials enables subsequent tailoring of the biomaterials to meet individual implantation needs. In our study, we have analyzed the biological, chemical, mechanical and thermal properties of photopolymerized poly(ethyleneglycol) diacrylate (PEGDA) and specific copolymers with different photoinitiator (PI) concentrations before and after applying a post treatment washing process. As comonomers, 1,3-butanediol diacrylate, pentaerythritol triacrylate and pentaerythritol tetraacrylate were used. The in vitro studies confirm the biocompatibility of all investigated copolymers. Uniaxial tensile tests show significantly lower tensile strength (82% decrease) and elongation at break (76% decrease) values for washed samples. Altered tensile strength is also observed for different PI concentrations: on average, 6.2 MPa for 1.25% PI and 3.1 MPa for 0.5% PI. The addition of comonomers lowers elongation at break on average by 45%. Moreover, our observations show glass transition temperatures (T

Drop-on-demand (DOD) inkjet printing enables exact dispensing and positioning of single droplets in the picoliter range. In this study, we investigate the long-term reproducibility of droplet formation of piezoelectric inkjet printed drug solutions using solvents with different volatilities. We found inkjet printability of EtOH/ASA drug solutions is limited, as there is a rapid forming of drug deposits on the nozzle of the printhead because of fast solvent evaporation. Droplet formation of c = 100 g/L EtOH/ASA solution was affected after only a few seconds by little drug deposits, whereas for c = 10 g/L EtOH/ASA solution, a negative affection was observed only after t = 15 min, while prominent drug deposits form at the printhead tip. Due to the creeping effect, the crystallizing structures of ASA spread around the nozzle but do not clog it necessarily. When there is a negative affection, the droplet trajectory is affected the most, while the droplet volume and droplet velocity are influenced less. In contrast, no formation of drug deposits could be observed for highly concentrated, low volatile DMSO-based drug solution of c = 100 g/L even after a dispensing time of t = 30 min. Therefore, low volatile solvents are preferable to highly volatile solvents to ensure a reproducible droplet formation in long-term inkjet printing of highly concentrated drug solutions. Highly volatile solvents require relatively low drug concentrations and frequent printhead cleaning. The findings of this study are especially relevant when high droplet positioning precision is desired, e.g., drug loading of microreservoirs or drug-coating of microneedle devices.

Beam–column connections are the most critical components of reinforced concrete (RC) structures. They serve as a load transfer path and take a significant portion of the overall shear. Joints in RC structures constructed with no seismic provisions have an insufficient capacity and ductility under lateral loading and can cause the progressive failure of the entire structure. The joint may fail in the shear prior to the connecting beam and column elements. Therefore, several modeling techniques have been devised in the past to capture the non-linear response of such joints. Modeling techniques used to capture the non-linear response of reinforced-concrete-beam–column joints range from simplified lumped plasticity models to detailed fiber-based finite element (FE) models. The macro-modeling technique for joint modeling is highly efficient in terms of the computational effort, analysis time, and computer memory requirements, and is one of the most widely used modeling techniques. The non-linear shear response of the joint panel and interface bond–slip mechanism are concentrated in zero-length linear and rotational springs while the connecting elements are modeled through elastic elements. The shear response of joint panels has also been captured through rigid panel boundary elements with rotational springs. The computational efficiency of these models is significantly high compared to continuum models, as each joint act as a separate supe-element. This paper aims to provide an up-to-date review of macro-modeling techniques for the analysis and assessment of RC-beam–column connections subjected to lateral loads. A thorough understanding of existing models is necessary for developing new mechanically adequate and computationally efficient joint models for the analysis and assessment of deficient RC connections. This paper will provide a basis for further research on the topic and will assist in the modification and optimization of existing models. As each model is critically evaluated, and their respective capabilities and limitations are explored, it should help researchers to improve and build on modeling techniques both in terms of accuracy and computational efficiency.

The objective of this study is the investigation of the transferability of the material extrusion process from conventional to robotic fabrication on silicone build plates for use in Enhanced Multipoint Moulding with Additive Attachments. Therefore, the study is based on two series of experiments. The first series of tests used a conventional plant extended by a silicone construction platform. In comparison, a six-axis industrial robot was chosen to produce the test specimens in the second series of tests. The comparisons of adhesion strengths and relative shape deviations are used to validate the transferability. The results of the tests show a very good transferability of the process from conventional to robotic production. Whilst angular specimen geometries can be transferred directly, for round specimen geometries, the results show a need for further adaptation to the robot kinematics. The round specimen geometries showed deviations in the surface quality caused by an over-extrusion in the robotic manufacturing. This over-extrusion results from the slicing process in combination with the robot control and may be avoided through further optimisation of the process parameters. Overall, to the best of our knowledge, this study is the first that successfully demonstrates the transfer of Fused Filament Fabrication (FFF) from a conventional system to manufacturing using robots on silicone build plates for the use in Enhanced Multipoint Moulding with Additive Attachments.

Temperature is an important abiotic factor that modulates all aspects of ectotherm physiology, including sensitivity to pollutants. Nanoparticles are emerging pollutants in coastal environments, and their potential to cause toxicity in marine organisms is a cause for concern. Here we studied the interactive effects of temperature (including seasonal and experimental warming) on sublethal toxicity of ZnO nanoparticles (nano-ZnO) in a model marine bivalve, the blue mussel Mytilus edulis. Molecular markers were used to assess the pollutant-induced cellular stress responses in the gills and the digestive gland of mussels exposed for 21 days to 10 μg l−1 and 100 μg l−1 of nano-ZnO or dissolved Zn under different temperature regimes including ambient temperature (10 °C and 15 °C in winter and summer, respectively) or experimental warming (+5 °C). Exposure to high concentration (100 μg l−1) of nano-ZnO caused oxidative injury to proteins and lipids and induced a marked apoptotic response indicated by increased transcript levels of apoptosis-related genes p53, caspase 3 and the MAPK pathway (JNK and p38) and decreased mRNA expression of anti-apoptotic Bcl-2. No significant induction of inflammatory cytokine-related response (TGF-β and NF-κB) of tissues was observed in nano-ZnO exposed-mussels. Furthermore, the oxidative injury and apoptotic response could differentiate the effects of nano-ZnO from those of dissolved Zn in the mussels. This study revealed that oxidative stress and stress-related transcriptional responses to nano-ZnO were strongly modified by warming and season in the mussels. No single biomarker could be shown to consistently respond to nano-ZnO in all experimental groups, which implies that multiple biomarkers are needed to assess nano-ZnO toxicity to marine organisms under the variable environmental conditions of coastal habitats.

Blockchain solutions offer efficient approaches for trustworthy data management, especially in the medical field when storing and processing sensitive patient data. Many institutional and industrial facilities have already recognized the importance of the technology for the health sector and have also formulated basic ideas, concepts and main use cases, but concrete implementations and executions are comparatively rare. This mini review examines current research on specific blockchain implementations in healthcare that go beyond the state of concept studies or theoretical implementation ideas and describes the most promising systems based on systematic literature research. The review shows that secure storage and easy access to complete patient data is becoming increasingly important. Blockchain technology can be used as a secure, transparent and digital way to meet these needs. Hybrid solutions consisting of conventional data storage and blockchain-based access management are increasingly being developed and implemented. The automation of blockchain processes through smart contracts is also recommended. The review further reveals ambiguities in the use of permissioned and permissionless blockchain frameworks, machine learning (ML) integration as well as the question of which data should be stored in the blockchain and how this should be viewed legally. Therefore, there is still a need for further research, especially on these aspects, in order to further establish the use of blockchains in healthcare.

Individually tailored drug delivery systems (DDSs) are considered one of the most promising therapeutic tools for the creation of safe and effective treatments. DDSs as a novel approach should be beneficial in curing systemic as well as local ailments, where a high topical concentration of the drug and a reduction of side effects are desirable. It could also be favorable for patients requiring customized treatments, showing atypical profiles of drug metabolism. Development of particular drug delivery devices require the selection of a suitable scaffold material, which should exhibit proper mechanical and biological properties, but also enable adjustment of the drug release according to a specific need. Thus, it is extremely important to expand the knowledge concerning potential DDS components. Poly(ethylene glycol) diacrylate (PEGDA) according to its properties can be easily used as a DDS resin and shaped into a desired structure with the employment of techniques based on photopolymerization, including some novel 3D printing techniques. As a continuation of our previous works, in this paper drug release studies from conventionally prepared PEGDA scaffolds are presented. We have shown that in PEGDA materials, the release profile of the low molecular weight model drug acetylsalicylic acid can be altered by water content. PEGDA as a delivery material should be further investigated to specify its potential as a comonomer and a matrix for pharmaceutical agents.

Digital Light Processing (DLP) enables high precision 3D-printing of photopolymers and holds promising potential for patient-specific implant solutions. On the material side, Poly(ethylene glycol) diacrylate (PEGDA) has emerged as an interesting material for use in biomedical applications. For adequate photopolymerization, a photoinitiator and a light absorber are necessary, using welldefined concentrations. This study shows preliminary results of DLP 3D-printing of different PEGDA hydrogel compositions with varying water content (90; 70; 50; 30; 10; 0 % w/w) as well as varying concentrations of a photoinitiator and a light absorber. Printing performance and accuracy are investigated by printing rectangular test samples as well as an anatomically customised tubular frontal sinus implant prototype. For basic mechanical characterisation, the hardness of the printed hydrogels is investigated using a Shore A durometer. The results show a decrease in printing accuracy and hardness with an increasing water content of the composition. There is a need to use a light absorber to reach high printing accuracy. This leads to a need for increasing photoinitiator concentration and prolonged light exposure to achieve proper printing performance.

Endoprostheses such as hip replacements are subject to wear. Lubrication of the joint interface plays a key role in the wear process, but the mechanisms of lubrication is challenging to understand. The main issue is the three-body abrasion which leads to a shorter life cycle. In order to improve the life cycle, the surfaces of the articulating components can be modified, for example by pulsed femtosecond-laser microstructuring. By microstructuring of the implant surface, the viscosity of the synovial fluid between the joint can be increased due to the non-Newtonian properties of the synovia. This leads to better lubrication and therefore lower particle abrasion. The objective of this study was to evaluate the impact of different microstructures on the viscosity of a joint fluid substitute. Various microstructures were investigated in a modified rheometer setup featuring a decreased gap size. As a test fluid, a synovial fluid substitute was used. The results show that an increase in the viscosity of the synovial fluid substitute can be achieved by microstructuring. An increase of viscosity of up to 20 % compared to the unstructured reference was observed with ring-structures with a diameter of 100 μm and a depth of 20 μm.

Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli‐responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin‐content oxidized alginate‐gelatin (ADA‐GEL) hydrogel is reported, offering 3D‐printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA‐GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D‐printability, and cytocompatibility. It is possible to prepare open‐porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D‐printable ADA‐GEL can be rendered conductive (ADA‐GEL‐PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical‐stimulation assisted tissue engineering.

This study presents a detailed characterization of self-organized nano- and microstructures on Ti6Al4V evoked by different scanning strategies and fluences with a 300 fs laser operating at a laser wavelength of 1030 nm. The resulting surface morphology was visualized via field emission scanning electron microscopy (FEG-SEM) images of the surface and cross-sections. X-ray diffraction (XRD)-analysis was performed to analyse changes in crystal structures. The chemical surface composition of the near-surface layer was determined by X-ray photoelectron spectroscopy (XPS). Results show a significant influence of heat accumulation while processing with high laser repetition rates on the formation, crystallinity and chemical composition of self-organized structures depending on the scanning strategy. The ablation with different laser scanning strategies led to varying dynamics of growth-mechanisms of self-organized structures, formation of intermetallic phases (Ti3Al), sub-oxides and oxides (Ti6O, TiO) as well as ions (Ti3+, Ti4+) in surface layer reliant on applied fluence. Furthermore, investigations revealed a heat-affected zone up to several micrometers in non-ablated material. © 2021 The Authors

Advanced engineering materials 23(11), 2001188 (2021). doi:10.1002/adem.202001188 special issue: "Neutrons and Synchrotron Radiation - Unique Tools for the Characterization of Materials", The 3D structural investigation of soft tissue samples under near physiological conditions is challenging as most established techniques require embedding, staining, or cutting samples. Such manipulations can induce artifacts or result in a tremendous workload by, e.g., the preparation of multiple 2D images to retrieve the volume information. A non-invasive technique allowing to image the soft tissue in a 3D fashion is propagation-based phase contrast computed tomography. We explore the methods' unique properties to assess the 3D distribution and size of human chondrocytes within collagen scaffolds in a liquid environment without embedding. To seek if the identification of differences in cell distribution is possible, we have seeded cartilage cells on collagen scaffolds that were unstimulated or stimulated by alternating electric fields for 7 days. Analysis of the 3D cell distributions reveals that the migration depth of the chondrocytes into the scaffold is nearly doubled along with the total number of cells due to the applied electric field. Further analysis shows no specific size distribution of the chondrogenic cells. Our results indicate that propagation-based phase contrast computed tomography is a suitable tool to determine the 3D distribution of cells within a biomaterial investigated under aqueous conditions., Published by Deutsche Gesellschaft fu��r Materialkunde, Frankfurt, M.

In cell-based therapies for cartilage lesions, the main problem is still the formation of fibrous cartilage, caused by underlying de-differentiation processes ex vivo. Biophysical stimulation is a promising approach to optimize cell-based procedures and to adapt them more closely to physiological conditions. The occurrence of mechano-electrical transduction phenomena within cartilage tissue is physiological and based on streaming and diffusion potentials. The application of exogenous electric fields can be used to mimic endogenous fields and, thus, support the differentiation of chondrocytes in vitro. For this purpose, we have developed a new device for electrical stimulation of chondrocytes, which operates on the basis of capacitive coupling of alternating electric fields. The reusable and sterilizable stimulation device allows the simultaneous use of 12 cavities with independently applicable fields using only one main supply. The first parameter settings for the stimulation of human non-degenerative chondrocytes, seeded on collagen type I elastin-based scaffolds, were derived from numerical electric field simulations. Our first results suggest that applied alternating electric fields induce chondrogenic re-differentiation at the gene and especially at the protein level of human de-differentiated chondrocytes in a frequency-dependent manner. In future studies, further parameter optimizations will be performed to improve the differentiation capacity of human cartilage cells.

The effect of chemical solvents on the wetting state of laser-structured surfaces over time is systematically examined in this paper. By using a 300-fs laser, nanostructures were generated on Ti6Al4V, subsequently cleaned in an ultrasonic bath with different solvents and stored in ambient air. The static contact angle showed significant differences for cleaning with various solvents, which, depending on the applied cleaning and time, amounted up to 100��. X-ray photoelectron spectroscopy analyses reveal that the cleaning of the laser-structured surfaces affects the surface chemistry and the aging behavior of the surfaces, even with highly volatile solvents. The effect of the chemical surface modification is particularly noticeable when using alcohols for cleaning, which, due to their OH groups, cause highly hydrophilic behavior of the surface after one day of storage. Over the course of 14 days, enrichment with organic groups from the atmosphere occurs on the surface, which leads to poorer wetting on almost every structured surface. In contrast, the cleaning in hexane leads to a fast saturation of the surface with long-chain carbon groups and thus to a time-independent hydrophobic behavior.

The prevalence of large bone defects is still a major problem in surgical clinics. It is, thus, not a surprise that bone-related research, especially in the field of bone tissue engineering, is a major issue in medical research. Researchers worldwide are searching for the missing link in engineering bone graft materials that mimic bones, and foster osteogenesis and bone remodeling. One approach is the combination of additive manufacturing technology with smart and additionally electrically active biomaterials. In this study, we performed a three-dimensional (3D) printing process to fabricate piezoelectric, porous barium titanate (BaTiO3) and hydroxyapatite (HA) composite scaffolds. The printed scaffolds indicate good cytocompatibility and cell attachment as well as bone mimicking piezoelectric properties with a piezoelectric constant of 3 pC/N. This work represents a promising first approach to creating an implant material with improved bone regenerating potential, in combination with an interconnected porous network and a microporosity, known to enhance bone growth and vascularization.

Bone defects can be the result of physiological atrophy, diseases, or medical intervention. Bone regeneration under electrical stimulation has been proven to be a promising approach in cell experiments. However, there is a lack of evidence of the respective effect in animal trials. This is limited because there are no fully implantable stimulators at hand. Therefore, the aim of our present study is the description of requirements and design of an implantable electrical stimulator for bone regeneration experiments.

Reconstruction of bone defects represents a serious issue for orthopaedic and maxillofacial surgeons, especially in extensive bone loss. Adipose-derived mesenchymal stem cells (ADSCs) with tri-calcium phosphates (TCP) are widely used for bone regeneration facilitating the formation of bone extracellular matrix to promote reparative osteogenesis. The present study assessed the potential of cell-scaffold constructs for the regeneration of extensive mandibular bone defects in a minipig model. Sixteen skeletally mature miniature pigs were divided into two groups: Control group and scaffolds seeded with osteogenic differentiated pADSCs (n = 8/group). TCP-PLGA scaffolds with or without cells were integrated in the mandibular critical size defects and fixed by titanium osteosynthesis plates. After 12 weeks, ADSCs seeded scaffolds (n = 7) demonstrated significantly higher bone volume (34.8% ± 4.80%) than scaffolds implanted without cells (n = 6, 22.4% ± 9.85%) in the micro-CT (p

Critical size bone defects are regularly treated by auto- and allograft transplantation. However, such treatments require to harvest bone from patient donor sites, with often limited tissue availability or risk of donor site morbidity. Not requiring bone donation, three-dimensionally (3D) printed implants and biomaterial-based tissue engineering (TE) strategies promise to be the next generation therapies for bone regeneration. We present here polylactic acid (PLA)-bioactive glass (BG) composite scaffolds manufactured by fused deposition modeling (FDM), involving the fabrication of PLA-BG composite filaments which are used to 3D print controlled open-porous and osteoinductive scaffolds. We demonstrated the printability of PLA-BG filaments as well as the bioactivity and cytocompatibility of PLA-BG scaffolds using pre-osteoblast MC3T3E1 cells. Gene expression analyses indicated the beneficial impact of BG inclusions in FDM scaffolds regarding osteoinduction, as BG inclusions lead to increased osteogenic differentiation of human adipose-derived stem cells in comparison to pristine PLA. Our findings confirm that FDM is a convenient additive manufacturing technology to develop PLA-BG composite scaffolds suitable for bone tissue engineering.

During the last years substantial effort was taken in order to provide an effective and safe pharmacotherapy that can be adjusted to the individual needs of patients. Stereolithography is a simple and accurate additive manufacturing technology. According to these characteristics, it may offer unique opportunities for the industrial fabrication of structured drug delivery systems (DDS), which can be tailored to individual needs. During the stereolithographic process photopolymerizable biomaterial is transformed, layer by layer, into the designed polymer DDS. Combined with inkjet printing in an innovative 3D building system it enables selective and precise incorporation of the drug depot into the basic body of the DDS. Poly(ethylene glycol) diacrylate (PEGDA), a hydrophilic and low-immunogenic compound, is a suitable material as drug depot in a photopolymerizable basic biomaterial for this purpose. By combination of PEGDA with other acrylates, the physical properties of the DDS can be adjusted towards the desired characteristics. Therefore, it should be possible to modify the drug release profile through the positioning of drug depots and the diffusion of the drug and adjust it for a wide range of applications. In this study we investigated basic biological and thermodynamic properties of conventionally photocured systems consisting of PEGDA and its coacrylates: 1,3-butanediol diacrylate and pentaerythritol triacrylate. Our preliminary outcomes demonstrate the hydrophilic character of the samples and the importance of a rinsing process. They also show that the addition of different amounts of co-monomers influence the glass transition temperature, which increases with increasing content of coacrylate. Therefore, PEGDA/comonomer composition can be used as a tool for the modification of drug release properties. Consequently, these materials may be regarded as interesting and promising components for DDS via novel additive manufacturing with the ability of highly controlled drug release.

Process and environmental parameters that influence manufacturing processes and results are of great importance in additive manufacturing processes such as Fused Deposition Modeling (FDM). The recording and analysis of these parameters is an important task of quality assurance (QA). For this purpose, sensors are increasingly used, which continuously record the environmental data during the printing process. Subsequently, algorithms for machine learning (ML) are suitable for the data analysis of data sequences as well as for the intelligent classification of the results in defined 3D printing condition classes. In this paper different state-of-the-art ML algorithms are presented, which enable a supervised learning classification approach of environmental sensor data (temperature, humidity, air pressure, gas particles) in the FDM process. For this purpose, a new data preparation method was developed which sequences different sensor time series data. FDM sensor parameters of various 3D printing conditions were recorded, preprocessed accordingly and saved in two differently sized datasets. Furthermore, a sensitivity analysis was carried out in order to examine the influence of the individual sensor parameters on the ML analyses. Interestingly, the air pressure values were characterized as being most relevant to the analyses. Better results were always achieved with the air pressure values than without. The air pressure values have a stabilizing effect on the analyses and reduce overfitting. In the further course of the investigations, tests were carried out on the two datasets of different sizes with all considered ML algorithms as well as tests with and without the air pressure values. There, the modern XceptionTime architecture has proven to be the most effective and robust against overfitting. XceptionTime can achieve excellent results with a minimum of 95% accuracy with both a small and a large database. The Macro F1-Scores are also always above 89% and indicate a good classification for all 3D printing conditions examined. The ML investigations were then compared in a proof of concept with 3D scan examinations established in quality assurance. The 3D scans of the printed FDM components could not provide any clear information about the different printing conditions and only the component surface could be analyzed. The ML analyses, especially with the XceptionTime architecture, enable an effective alternative to quickly and easily differentiate between different 3D printing conditions. The ML time series classification presented in this work is accordingly well suited for use in an industrial environment and, with special optimizations, can be effectively applied in practice to support quality assurance in additive manufacturing. This quality assurance approach is completely new and offers immense potential to increase trust in and acceptance of additive manufacturing processes.

Current research activities focus on personalized, comfortable and safe products for systemic or local drug application in patients. Poly(ethylene glycol) diacrylate is in particular interest as a drug delivery material, as it shows appropriate biological properties such as hydrophilicity and low toxicity. Additionally, as an easily photopolymerizable compound it can be also utilized for the production of scaffolds with the use of different techniques such as stereolithography. Even though it is often used as a biomaterial or as a copolymer in many photopolymer systems for drug delivery, thermomechanical analysis and basic understanding are rare. Therefore, we investigated the tensile stress and the glass transition temperature of pure PEGDA and of its copolymers with 1,3-butanediol diacrylate or pentaerythritol triacrylate, as a function of the photoinitiator (PI) or acrylate concentration. Additionally, we demonstrated that the washing procedure decreases the tensile stress values. We showed, that by the means of composing PEGDA with these, it is possible to influence thermomechanical properties of the sample. Our outcomes have revealed, that there is no clear influence of the PI concentration on the thermomechanical properties. However there is an influence of the monomer concentration. Therefore, it should be possible to modify drug release profiles in future experiments.

Inkjet printing has become essential for pharmaceutical research as well as biomedical applications. It is a promising tool to meet future challenges in patientindividual designed pharmaceuticals and implants. In this context, the main areas of use are high-throughput screening (HTS), drug-loaded microparticles, drug formulation and oral dose development, 3D-printing/bioprinting as well as coating of implants. This study deals with the latter. In view of promising applications for localized coating and functionalization of implant surfaces this work shows preliminary results on inkjet printing of the polymer poly(2- ethyl-2-oxazoline) (PetOx), a protein repellent polymer (PRP). To deposit single droplets with small volumes (~500 pl) of aqueous PetOx solution (50 g/l), printing parameters were determined for the piezo-driven drop-ondemand inkjet printhead NanoTip J, operating in a Nanoplotter 2.1 (both from GeSiM mbH, Germany). Different printing strategies are demonstrated by varying droplet spacing and drying time while printing on hydrophilic glass substrate. Printing and stacking of almost uniform polymer lines (width ~ 200 μm) is demonstrated.

Three-dimensional (3D) printing has become a popular technique in many areas. One emerging field is the use of 3D printing for the development of 3D drug delivery systems (DDS) and drug-loaded medical devices. This article describes a novel concept for the fabrication of timecontrolled drug delivery systems based on stereolithography combined with inkjet printing. An inkjet printhead and an UV-LED light source have been integrated into an existing stereolithography system. Inkjet printing is used to selectively incorporate active pharmaceutical ingredients (API) during a stereolithographic 3D printing process. In an initial experimental study, poly (ethylene glycol) diacrylate (PEGDA) was used as polymer whereas 2-Hydroxy-4´-(2- hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) and Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) were used as photoinitiators. Basic structures could be manufactured successfully by the new hybrid 3D printing system.

The technology of pharmaceutical drug delivery systems (DDS) as an individual and adjustable tool for drug administration has been intensively developed in the last years. Additive manufacturing (AM) techniques, such as stereolithography, are a promising approach towards DDS scaffold manufacturing. Stereolithography, by using layerby- photo-polymerisation, creates DDS scaffolds with highly controlled 3D geometry. Combined with inkjet printing it allows a very precise positioning of the drug depot in the basic scaffold and therefore also a better control of the drug release. Furthermore, this hybrid AM technique also allows for the creation of a multi-drug DDS with a several drug depots localized in desired positions within the scaffold. Determination of the scaffold and drug depot material properties is one of the initial steps for such novel DDS development. Basic characteristics, such as stiffness, elasticity or glass transition temperature (Tg), are important for designing and adapting the material for biomedical application. The photosensitive poly(ethylene glycol) diacrylate (PEGDA) can be easily formed into a desired biocompatible scaffold geometry via stereolithography. In this study we have focused on the evaluation of PEGDA (Mn=700 g/mol) as a pure and copolymer system in combination with other acrylates (butanediol diacrylate, pentaerythritol triacrylate) as possible materials for DDS using this novel hybrid AM technique. Irgacure 2959, a biocompatible photoinitiator (PI), was used as a radical starter for photopolymerisation. Samples varying in PI and coacrylate concentration were prepared by conventional photopolymerisation. Physico-chemical analyses of the samples were performed and several parameters, such as stiffness, elongation at break and glass transition temperatures, were determined.

The deep understanding of cancer and tumor genesis, as well as the development of new therapy strategies still remains one of the emerging challenges in modern medicine. To meet these challenges it seems to be absolutely necessary to overcome the drawbacks of the established 2D in vitro models. Especially the missing microenvironment of the tumor, which means the absence of stroma and immune cells, results in a missing cell-cell and cell-stroma interaction as well as disrupted functional communication pathways. Modern 3D culture systems and 3D printing or rather bioprinting technologies attempt to solve this issue and aim to closely mimic natural tumor microenvironment. In this preliminary work we are going to present the first steps of establishing an artificial 3D tumor model utilising a low cost 3D printer. Therefore the printer had been modified with an open-source syringe pump to become a functional bioprinter using viscosity modulated alginate hydrogel. In the first attempts L929 mouse fibroblasts, which are an integral component of natural stroma, had been incorporated into the hydrogel matrix and printed into scaffolds. Subsequent to the printing process the scaffolds got ionically crosslinked with a 5% w/v aqueous solution of CaCl2 to become mechanically stable. After three days of cultivation viability testing had been performed by utilising FDG staining and PET CT to obtain a volumetric viability measurement. The viability imaging showed vital cells homogeneously distributed in the scaffold and therefore stands as an evidence for a working low cost bioprinting process and a successful first step for the development of an artificial 3D tumor model.

For the development of a novel, user-friendly and low cost point-of-care diagnostic device for the detection of disease specific biomarker a flow optimised design of the test system has to be investigated. The resulting test system is characterised by a reduced execution period, a reduction of execution steps and an integrated waste management. Based on previous results, the current study focused on the design implementation of the fluidic requirements, e. g. tightness, inside the test device. With the help of fluid flow simulations (CFD – computational fluid dynamics) the flow behaviour inside the test device was analysed for different designs and arrangements. Prototypes generated from additive manufacturing technologies (PolyJet modeling) are used for validating the simulation results and further experimental tests.

This study investigated the wetting behavior of Ti6Al4V surfaces that were groove-structured by means of femtosecond laser irradiation. The material was treated under ambient air conditions by use of a laser wavelength of 1030 nm and a pulse duration of 300 fs. Highly accurate structures with a gap width of 20 &micro, m, a gap depth of 10 &micro, m, and varying strut widths (1&ndash, 300 &micro, m) were generated and the contact angles in parallel and perpendicular direction were determined using sessile drop method with ultrapure water 1, 8, and 15 days after irradiation. All deterministic surfaces exhibited a pronounced contact angle change over time. The structures showed a strong anisotropic wetting behavior with a maximum contact angle aspect ratio of 2.47 at a strut width of 40 &micro, m and a maximum difference between the parallel and perpendicular contact angle of 47.9&deg, after 1 day.

Nano- and microstructured titanium surfaces have recently attracted attention in the field of regenerative medicine because of the influence which surface characteristics such as roughness and wettability can have on cellular processes. This study focuses on the correlation of surface properties (wettability and nano/micro texture) of laser-structured Ti6Al4V samples with pronounced cell adhesion. Samples were structured with multiple laser parameters in order to create a range of surface properties. Surface characterization was performed by contact angle measurements 1 and 7 days after laser processing. The arithmetic mean roughness of the material surface in an area (Sa) was determined by means of confocal laser scanning microscopy (CLSM). Immediately after wettability tests of the laser-structured surfaces, in vitro experiments with human MG-63 osteoblasts were carried out. For this purpose, the cell morphology and actin cytoskeleton organization were analyzed using CLSM and scanning electron microscopy. On rough microstructures with deep cavities, the cell growth and spreading were inhibited. An improved cellular adhesion and growth on nanostructured and sinusoidal microstructured surfaces could be demonstrated, regardless of hydrophilicity of the surfaces.