Translational Aspects of 3D and 4D Printing and Bioprinting.

Three-dimensional (3D) printed medical devices include orthopedic and craniofacial implants, surgical tools, and external prosthetics that have been directly used in patients. While the advances of additive manufacturing techniques in the production of medical devices have been on the rise, clinical translation of living cellular constructs face significant limitations in terms of regulatory affairs, process technology, and materials development. In this perspective, the current status-quo of 3D and four-dimensional (4D) (bio)printing is summarized, current advancements are discussed and the challenges that need to be addressed for improved industrial translation and clinical applications of bioprinting are highlighted.

FRESH Bioprinting of Dynamic Hydrazone-Cross-Linked Synthetic Hydrogels.

Dynamic covalent chemistry is an attractive cross-linking strategy for hydrogel bioinks due to its ability to mimic the dynamic interactions that are natively present in the extracellular matrix. However, the inherent challenges in mixing the reactive precursor polymers during printing and the tendency of the soft printed hydrogels to collapse during free-form printing have limited the use of such chemistry in 3D bioprinting cell scaffolds. Herein, we demonstrate 3D printing of hydrazone-cross-linked poly(oligoethylene glycol methacrylate) (POEGMA) hydrogels using the freeform reversible embedding of suspended hydrogels (FRESH) technique coupled with a customized low-cost extrusion bioprinter.

Hydrogels for Tissue Engineering: Addressing Key Design Needs Toward Clinical Translation.

While the soft mechanics and tunable cell interactions facilitated by hydrogels have attracted significant interest in the development of functional hydrogel-based tissue engineering scaffolds, translating the many positive results observed in the lab into the clinic remains a slow process. In this review, we address the key design criteria in terms of the materials, crosslinkers, and fabrication techniques useful for fabricating translationally-relevant tissue engineering hydrogels, with particular attention to three emerging fabrication techniques that enable simultaneous scaffold fabrication and cell loading: 3D printing, tissue engineering, and cell electrospinning. In particular, we emphasize strategies for manufacturing tissue engineering hydrogels in which both macroporous scaffold fabrication and cell loading can be conducted in a single manufacturing step - electrospinning, 3D printing, and tissue engineering.

Click Chemistry Hydrogels for Extrusion Bioprinting: Progress, Challenges, and Opportunities.

The emergence of 3D bioprinting has allowed a variety of hydrogel-based "bioinks" to be printed in the presence of cells to create precisely defined cell-loaded 3D scaffolds in a single step for advancing tissue engineering and/or regenerative medicine. While existing bioinks based primarily on ionic cross-linking, photo-cross-linking, or thermogelation have significantly advanced the field, they offer technical limitations in terms of the mechanics, degradation rates, and the cell viabilities achievable with the printed scaffolds, particularly in terms of aiming to match the wide range of mechanics and cellular microenvironments. Click chemistry offers an appealing solution to this challenge given that proper selection of the chemistry can enable precise tuning of both the gelation rate and the degradation rate, both key to successful tissue regeneration; simultaneously, the often bio-orthogonal nature of click chemistry is beneficial to maintain high cell viabilities within the scaffolds.

A Hybrid Soluble gp130/Spike-Nanobody Fusion Protein Simultaneously Blocks Interleukin-6 -Signaling and Cellular Infection with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce mild to life-threatening symptoms. Especially individuals over 60 years of age or with underlying comorbidities, including heart or lung disease and diabetes, or immunocompromised patients are at a higher risk. Fatal multiorgan damage in coronavirus disease 2019 (COVID-19) patients can be attributed to an interleukin-6 (IL-6)-dominated cytokine storm.

Fabricating Degradable Thermoresponsive Hydrogels on Multiple Length Scales via Reactive Extrusion, Microfluidics, Self-assembly, and Electrospinning.

While various smart materials have been explored for a variety of biomedical applications (e.g., drug delivery, tissue engineering, bioimaging, etc.

Dynamically Cross-Linked Self-Assembled Thermoresponsive Microgels with Homogeneous Internal Structures.

The internal morphology of temperature-responsive degradable poly(N-isopropylacrylamide) (PNIPAM) microgels formed via an aqueous self-assembly process based on hydrazide and aldehyde-functionalized PNIPAM oligomers is investigated. A combination of surface force measurements, small angle neutron scattering (SANS), and ultrasmall angle neutron scattering (USANS) was used to demonstrate that the self-assembled microgels have a homogeneously cross-linked internal structure. This result is surprising given the sequential addition process used to fabricate the microgels, which was expected to result in a densely cross-linked shell-diffuse core structure.

Microfluidic production of degradable thermoresponsive poly(N-isopropylacrylamide)-based microgels.

Highly monodisperse and hydrolytically degradable thermoresponsive microgels on the tens-to-hundreds of micron size scale have been fabricated based on simultaneous on-chip mixing and emulsification of aldehyde and hydrazide-functionalized poly(N-isopropylacrylamide) precursor polymers. The microfluidic chip can run for extended periods without upstream gelation and can produce monodisperse (<10% particle size variability) microgels on the size range of ∼30-90 μm, with size tunable according to the flow rate of the oil continuous phase. Fluorescence analysis indicates a uniform distribution of each reactive pre-polymer inside the microgels while micromechanical testing suggests that smaller microfluidic-produced microgels exhibit significantly higher compressive moduli compared to bulk hydrogels of the same composition, an effect we attribute to improved mixing (and thus crosslinking) of the precursor polymer solutions within the microfluidic device.

A transdisciplinary account of water research.

Water research is introduced from the combined perspectives of natural and social science and cases of citizen and stakeholder coproduction of knowledge. Using the overarching notion of transdisciplinarity, we examine how interdisciplinary and participatory water research has taken place and could be developed further. It becomes apparent that water knowledge is produced widely within society, across certified disciplinary experts and noncertified expert stakeholders and citizens.

Applicability of salt reduction strategies in pizza crust.

In an effort to reduce population-wide sodium intake from processed foods, due to major health concerns, several different strategies for sodium reduction in pizza crust without any topping were evaluated by sensory analyses. It was possible to reduce sodium by 10% in one single step or to replace 30% of NaCl by KCl without a noticeable loss of salty taste. The late addition of coarse-grained NaCl (crystal size: 0.

Temperature-Induced Assembly of Monodisperse, Covalently Cross-Linked, and Degradable Poly(N-isopropylacrylamide) Microgels Based on Oligomeric Precursors.

A simple, rapid, solvent-free, and scalable thermally driven self-assembly approach is described to produce monodisperse, covalently cross-linked, and degradable poly(N-isopropylacrylamide) (PNIPAM) microgels based on mixing hydrazide (PNIPAM-Hzd) and aldehyde (PNIPAM-Ald) functionalized PNIPAM precursors. Preheating of a seed PNIPAM-Hzd solution above its phase transition temperature produces nanoaggregates that are subsequently stabilized and cross-linked by the addition of PNIPAM-Ald. The ratio of PNIPAM-Hzd:PNIPAM-Ald used to prepare the microgels, the time between PNIPAM-Ald addition and cooling, the temperature to which the PNIPAM-Hzd polymer solution is preheated, and the concentration of PNIPAM-Hzd in the initial seed solution can all be used to control the size of the resulting microgels.

Dopaminergic foundations of schizotypy as measured by the German version of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)-a suitable endophenotype of schizophrenia.

The concept of schizotypy or "psychosis proneness" captures individual differences in perceptual, cognitive, and affective experiences that may relate to a range of psychotic disorders. The concept is an important way to assess the contribution of pre-existing psychological and genetically based biological features to the development of illnesses such as schizophrenia (so called endophenotypes). The Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) is a widely used multi-dimensional measure of the construct and consists of four scales which mirror several groups of psychotic symptoms: Unusual Experiences (UnEx; positive symptoms), Cognitive Disorganization (CogDis; cognitive symptoms), Introvertive Anhedonia (IntAn; negative symptoms), and Impulsive Nonconformity (ImpNon; impulsive and antisocial symptoms).

Genetic variants within the dopaminergic system interact to modulate endocrine stress reactivity and recovery.

Catecholamines modulate endocrine stress reactivity by affecting regulatory influences of extra-hypothalamic brain structures on hypothalamus-pituitary-adrenal (HPA)-axis. Therefore, we aimed to investigate combined effects of functional allelic variations that affect dopamine availability in both cortical (COMT Val¹⁵⁸Met polymorphism) and subcortical (DAT1 VNTR) brain regions on HPA-axis reactivity to psychosocial stress. By using a standardized laboratory stress task (public speaking) we obtained saliva cortisol samples during stress exposure and an extended recovery period in 100 healthy male adults.

The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.

Background: Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity.

Aggression--interactions of serotonin and testosterone in healthy men and women.

Serotonin (5-HT) and testosterone (T) have both been implicated in the regulation of aggression. Findings in humans however are very inconclusive, with respect to main effects of either system. Animal models implicate T to modulate 5-HT system activity, and furthermore have shown behaviorally relevant interactions of T and 5-HT with respect to aggression.