In tissue engineering, the production of well-defined scaffolds with a porous architecture from degradable polymers is of great interest. Detailed designs have become feasible through the development of additive manufacturing. A small nozzle size is needed to obtain detailed scaffold structures, and careful control of the rheological properties is therefore required during production. A lower viscosity of the melt allows for easier printability, but a high molar mass is required to produce scaffolds that can retain mechanical properties over the time needed for tissue regeneration. An additional challenge of using degradable polymers with high molar mass in any melt-based processing is that thermal degradation can reduce the molar mass during the production stage. To utilise medical grade degradable polymers whilst limiting the thermal degradation a rheological analysis of the most commonly used commercial medical-grade degradable synthetic polymers was performed. Their rheological behaviours aided in setting process parameters for two different melt-based additive manufacturing routes. The variation in thermal degradation in the two routes was assessed, and the parameters were adjusted to minimise it.

A nondegradative additive manufacturing method was designed, and knowledge regarding printability was developed based on rheological analysis and polymer characterisation methods. This knowledge was applied to the copolymer poly(e-caprolactone-co-p-dioxanone) developed within the group to fabricate pliable scaffolds for tissue engineering with an increased rate of hydrolysis in comparison to poly(e-caprolactone). In addition to the selection of the polymer and process parameters, the mechanical properties were also controlled through the structural design. Poly(e-caprolactone) was used as a model material to show how the mechanical properties of scaffolds could be controlled based on the design solely. The results showed that the stiffness could be reduced by more than a factor of 10 through tuning of the design, resulting in soft pliable scaffold structures.

Food contact materials (FCMs) i.e. materials that food is packaged or handled in, must be safe for their intended use. European FCM legislation uses a risk-based approach, with a cornerstone of FCM’s safety evaluation being measurement of migration of substances from FCMs to food simulants. The standard methods mainly developed for plastic FCMs are not always suitable for less inert and moisture sensitive materials such as paper and board. However, these are becoming increasingly common as FCMs e.g. to replace single-use plastics. In addition, there is a drive to further use recycled materials. To support this development, new methods for assessing the safety of these materials are needed. In the present feasibility study, a hydrogel crosslinked through freeze-thawing of poly(vinyl alcohol) was evaluated as a food simulant for moist foods. The migration of surrogate compounds from a spiked paperboard to the hydrogel was determined and compared to the migration to a real moist food (a slice of apple), the commonly used modified polyphenylene oxide (MPPO) and a water extract. Migration of polar surrogates to the hydrogel correlated well with the migration to the apple slice. However, our results indicate that the hydrogel is less suitable as simulant for non-polar surrogates. Overall, the study demonstrates the potential of this hydrogel-based simulant for improving risk assessment of less inert FCMs. 

We examine the influence of surface charge on the percolation, gel-point and phase behavior of cellulose nanocrystal (CNC) suspensions in relation to their nonlinear rheological material response. Desulfation decreases CNC surface charge density which leads to an increase in attractive forces between CNCs. Therefore, by considering sulfated and desulfated CNC suspensions, we are comparing CNC systems that differ in their percolation and gel-point concentrations relative to their phase transition concentrations. The results show that independently of whether the gel-point (linear viscoelasticity, LVE) occurs at the biphasic - liquid crystalline transition (sulfated CNC) or at the isotropic - quasi-biphasic transition (desulfated CNC), the nonlinear behavior appears to mark the existence of a weakly percolated network at lower concentrations. Above this percolation threshold, nonlinear material parameters are sensitive to the phase and gelation behavior as determined in static (phase) and LVE conditions (gel-point). However, the change in material response in nonlinear conditions can occur at higher concentrations than identified through polarized optical microscopy, suggesting that the nonlinear deformations could distort the suspensions microstructure such that for example a liquid crystalline phase (static) suspension could show microstructural dynamics similar to a biphasic system.

The current global sodium consumption exceeds recommended daily intakes and there is a great need to reduce the sodium content in foods for a healthier society. The current study investigated the effect of combining sensory interaction principles and heterogeneous distribution of NaCl in bread on sensory properties, structure, and NaCl distribution. Breads were prepared in three different arrangements of NaCl distribution: homogenous, layered, and layered with lactic acid. Within each arrangement, four NaCl levels were tested. The breads were evaluated by a sensory panel for perceived saltiness, sourness, and qualitative texture, measured for stiffness, and the NaCl distribution was determined by X-ray fluorescence microscopy (XFM). Perceived saltiness was significantly enhanced in breads beyond heterogeneous NaCl distribution when lactic acid was added. Stiffness measurements were affected by layering of bread, the layers without NaCl were stiffer with an increase in overall salt concentration. The heterogeneous distribution of NaCl in layered breads could be visualised by XFM and textural consequences of layering bread are discussed. The current study demonstrates the potential of combining principles of pulsation of taste and sensory interactions together to enhance salt perception, and hence suggesting the approach as a possible further strategy for NaCl reduction in bread.

Current standard wound care involves dressings that provide moisture and protection; however, dressings providing active healing are still scarce and expensive. We aimed to develop an ecologically sustainable 3D printed bioactive hydrogel-based topical wound dressing targeting healing of hard-to-heal wounds, such as chronic or burn wounds, which are low on exudate. To this end, we developed a formulation composed of renewable marine components; purified extract from unfertilized salmon roe (heat-treated X, HTX), alginate from brown seaweed, and nanocellulose from tunicates. HTX is believed to facilitate the wound healing process. The components were successfully formulated into a 3D printable ink that was used to create a hydrogel lattice structure. The 3D printed hydrogel showed a HTX release profile enhancing pro-collagen I alpha 1 production in cell culture with potential of promoting wound closure rates. The dressing has recently been tested on burn wounds in Göttingen minipigs and shows accelerated wound closure and reduced inflammation. This paper describes the dressings development, mechanical properties, bioactivity, and safety. 

As life expectancy increases so do age related problems such as swallowing disorders, dysphagia, which affects 10%–30% of people over 65 years old. For dysphagia patients the texture and rheological properties of the food, and the bolus, is critical to avoid choking and pneumonia. Texture modified foods, timbals, are often served to these patients due to their ease of swallowing. The main concern with these foods is that they do not look visually alike the food they replace, which can decrease the patient’s appetite and lead to reduced food intake and frailty. This study aims to improve both the visual appearance of texturized food as well as the energy density and fiber content of the timbal formulation. 3D scanning and additive manufacturing (3D Printing) were used to produce meals more reminiscent of original food items, increasing their visual appeal. Rheology was used to ensure the original flow profile was maintained as the timbal was reformulated by reducing starch contents and partially replacing with dietary fibers. The amount of starch was reduced from 8.7 wt% in the original formulation to 3.5 wt% and partially replaced with 3 wt% citrus fiber, while maintaining properties suitable for both swallowing and 3D printing. The resulting formulation has improved nutritional properties, while remaining suitable for constructing visually appealing meals, as demonstrated by 3Dprinting a chicken drumstick from a model generated with 3D scanning.

Additive manufacturing is suitable for producing complex geometries; however, variation in thermo-mechanical properties are observed during one batch cycle when degradable aliphatic polyesters of medical grade are used in melt extrusion-based methods. This is one important reason for why additive manufacturing has not yet been fully utilised to produce degradable medical implants. Herein, the internal variation has been minimised during one batch cycle by assessing the effect of different processing parameters when using commercially available medical grade copolymers. To minimise the molar mass, thermal and mechanical variation within one batch cycle, the rheological fingerprint of the commercially available medical grade poly(L-lactide-co-ε-caprolactone) and poly(L-lactide-co-trimethylene carbonate) has been correlated to the process parameters of the ARBURG Plastic Freeforming. An increase in the temperature up to 220°C and the associated increase in pressure are beneficial for the viscoelastic and thermally stable poly(L-lactide-co-ε-caprolactone). In contrast, a temperature below 220°C should be used for the poly(L-lactide-co-trimethylene carbonate) to reduce the variation in strain at break during one batch cycle. The residence time is decreased through the increase of the discharge parameter. An increase in temperature is however required to reduce the viscosity of the polymer and allow the pressure to stay within the machine limitations at higher discharge parameters. The results are highly relevant to the development of additive manufacturing for the production of degradable medical devices with identical properties. In fact, Food and Drug Administration guidelines for additive manufacturing of medical implants specify the need to control changes in material properties during the process.

The advancement of 3D printing technologies in the fabrication of degradable scaffolds for tissue engineering includes, from the standpoint of the polymer chemists, an urgent need to develop new materials that can be used as ink and are suitable for medical applications. Here, we demonstrate that a copolymer of epsilon-caprolactone (CL) with low amounts of p-dioxanone (DX) (15 mol %) is a degradable and printable material that suits the requirements of melt extrusion 3D printing technologies, including negligible degradation during thermal processing. It is therefore a potential candidate for soft tissue regeneration. The semicrystalline CL/DX copolymer is processed at a lower temperature than a commercial polycaprolactone (PCL), shaped as a filament for melt extrusion 3D printing and as porous and pliable scaffolds with a gradient design. Scaffolds have Young's modulus in the range of 60-80 MPa, values suitable for provision of structural support for damaged soft tissue such as breast tissue. SEM and confocal microscope indicate that the CL/DX copolymer scaffolds support adipose stem cell attachment, spreading, and proliferation.

Degradable porous polymeric structures are attractive candidates for biological tissue scaffolds, and adequate mechanical, transport, chemical and biological properties determine their functionality. Aside from the properties of polymer-based materials, the scaffold's meso-structure controls its elasticity at the organ length-scale. This study investigated the effect of the meso-structure on scaffolds' mechanical and transport properties using finite element analysis (FEA) and computational fluid dynamics (CFD). A number of poly (ε-caprolactone) (PCL) - based scaffolds were 3D printed, analyzed by microcomputed tomography (micro-CT) and mechanically tested. We found that the gradient (G) and gradient and staggered (GS) meso-structure designs led to a higher scaffold permeability, a more homogeneous flow inside the scaffold, and a lower wall shear stress (WSS) in comparison with the basic (B) meso-structure design. The GS design resulted in scaffold stiffness as low as 1.07/0.97 MPa under compression/tension, figures that are comparative with several soft tissues. Image processing of micro-CT data demonstrated that the imposed meso-structures could have been adequately realized through 3D printing, and experimental testing validated FEA analysis. Our results suggest that the properties of 3D-printed PCL-based scaffolds can be tuned via meso-structures toward soft tissue engineering applications. The biological function of designed scaffolds should be further explored in-situ studies.

This paper investigates a strategy to convert hydrophilic cellulose nanofibrils (CNF) into a hydrophobic highly cross-linked network made of cellulose nanofibrils and inorganic nanoparticles. First, the cellulose nanofibrils were chemically modified through an esterification reaction to produce a nanocellulose-based macroinitiator. Barium titanate (BaTiO3, BTO) nanoparticles were surface-modified by introducing a specific monomer on their outer-shell surface. Finally, we studied the ability of the nanocellulose-based macroinitiator to initiate a single electron transfer living radical polymerization of stearyl acrylate (SA) in the presence of the surface-modified nanoparticles. The BTO nanoparticles will transfer new properties to the nanocellulose network and act as a cross-linking agent between the nanocellulose fibrils, while the monomer (SA) directly influences the hydrophilic-lipophilic balance. The pristine CNF and the nanoparticle cross-linked CNF are characterized by FTIR, SEM, and solid-state 13C NMR. Rheological and dynamic mechanical analyses revealed a high dregee of cross-linking.

A challenge in the extrusion-based bioprinting is to find a bioink with optimal biological and physicochemical properties. The aim of this study was to evaluate the influence of wood-based cellulose nanofibrils (CNF) and bioactive glass on the rheological properties of gelatin-alginate bioinks and the initial responses of bone cells embedded in these inks. CNF modulated the flow behavior of the hydrogels, thus improving their printability. Chemical characterization by SEM-EDX and ion release analysis confirmed the reactivity of the BaG in the hydrogels. The cytocompatibility of the hydrogels was shown to be good, as evidenced by the viability of human osteoblast-like cells (Saos-2) in cast hydrogels. For bioprinting, 4-layer structures were printed from cell-containing gels and crosslinked with CaCl2. Viability, proliferation and alkaline phosphatase activity (ALP) were monitored over 14 days. In the BaG-free gels, Saos-2 cells remained viable, but in the presence of BaG the viability and proliferation decreased in correlation with the increased viscosity. Still, there was a constant increase in the ALP activity in all the hydrogels. Further bioprinting experiments were conducted using human bone marrow-derived mesenchymal stem cells (hBMSCs), a clinically relevant cell type. Interestingly, hBMSCs tolerated the printing process better than Saos-2 cells and the ALP indicated BaG-stimulated early osteogenic commitment. The addition of CNF and BaG to gelatin-alginate bioinks hold great potential for bone tissue engineering applications.