Clinical applicability of optogenetic gene regulation

The field of optogenetics is rapidly growing in relevance and number of developed tools. Among other things, the optogenetic repertoire includes light-responsive ion channels and methods for gene regulation. This review will be confined to the optogenetic control of gene expression in mammalian cells as suitable models for clinical applications. Here optogenetic gene regulation might offer an excellent method for spatially and timely regulated gene and protein expression in cell therapeutic approaches. Well-known systems for gene regulation, such as the LOV-, CRY2/CIB-, PhyB/PIF-systems, as well as other, in mammalian cells not yet fully established systems, will be described. Advantages and disadvantages with regard to clinical applications are outlined in detail. Among the many unanswered questions concerning the application of optogenetics, we discuss items such as the use of exogenous chromophores and their effects on the biology of the cells and methods for a gentle, but effective gene transfection method for optogenetic tools for in vivo applications

Vascular implants – new aspects for in situ tissue engineering

Conventional synthetic vascular grafts require ongoing anticoagulation, and autologous venous grafts are often not available in elderly patients. This review highlights the development of bioartificial vessels replacing brain-dead donor- or animal-deriving vessels with ongoing immune reactivity. The vision for such bio-hybrids exists in a combination of biodegradable scaffolds and seeding with immune-neutral cells, and here different cells sources such as autologous progenitor cells or stem cells are relevant. This kind of in situ tissue engineering depends on a suitable bioreactor system with elaborate monitoring systems, three-dimensional (3D) visualization and a potential of cell conditioning into the direction of the targeted vascular cell phenotype. Necessary bioreactor tools for dynamic and pulsatile cultivation are described. In addition, a concept for design of vasa vasorum is outlined, that is needed for sustainable nutrition of the wall structure in large caliber vessels. For scaffold design and cell adhesion additives, different materials and technologies are discussed. 3D printing is introduced as a relatively new field with promising prospects, for example, to create complex geometries or micro-structured surfaces for optimal cell adhesion and ingrowth in a standardized and custom designed procedure. Summarizing, a bio-hybrid vascular prosthesis from a controlled biotechnological process is thus coming more and more into view. It has the potential to withstand strict approval requirements applied for advanced therapy medicinal products

Recent advances in melt electro writing for tissue engineering for 3D printing of microporous scaffolds for tissue engineering

Melt electro writing (MEW) is a high-resolution 3D printing technique that combines elements of electro-hydrodynamic fiber attraction and melts extrusion. The ability to precisely deposit micro- to nanometer strands of biocompatible polymers in a layer-by-layer fashion makes MEW a promising scaffold fabrication method for all kinds of tissue engineering applications. This review describes possibilities to optimize multi-parametric MEW processes for precise fiber deposition over multiple layers and prevent printing defects. Printing protocols for nonlinear scaffolds structures, concrete MEW scaffold pore geometries and printable biocompatible materials for MEW are introduced. The review discusses approaches to combining MEW with other fabrication techniques with the purpose to generate advanced scaffolds structures. The outlined MEW printer modifications enable customizable collector shapes or sacrificial materials for non-planar fiber deposition and nozzle adjustments allow redesigned fiber properties for specific applications. Altogether, MEW opens a new chapter of scaffold design by 3D printing

High unawareness of chronic kidney disease in Germany

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular events, hospitalizations, end stage renal disease and mortality. Main risk factors for CKD are diabetes, hypertension, and older age. Although CKD prevalence is about 10%, awareness for CKD is generally low in patients and physicians, hindering early diagnosis and treatment. We analyzed baseline data of 3305 participants with CKD Stages 1–4 from German cohorts and registries collected in 2010. Prevalence of CKD unawareness and prevalence ratios (PR) (each with 95%-confidence intervals) were estimated in categories of age, sex, CKD stages, BMI, hypertension, diabetes and other relevant comorbidities. We used a log-binomial regression model to estimate the PR for CKD unawareness for females compared to males adjusting for CKD stage and CKD risk factors. CKD unawareness was high, reaching 71% (68–73%) in CKD 3a, 49% (45–54%) in CKD 3b and still 30% (24–36%) in CKD4. Prevalence of hypertension, diabetes or cardiovascular comorbidities was not associated with lower CKD unawareness. Independent of CKD stage and other risk factors unawareness was higher in female patients (PR = 1.06 (1.01; 1.10)). Even in patients with CKD related comorbidities, CKD unawareness was high. Female sex was strongly associated with CKD unawareness. Guideline oriented treatment of patients at higher risk for CKD could increase CKD awareness. Patient–physician communication about CKD might be amendable. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

A promising protocol for the endothelialization of vascular grafts in an instrumented rotating bioreactor towards clinical application

Pre-endothelialization of a tissue-engineered vascular graft before implantation aims to prevent thrombosis and immunoreactions. This work demonstrates a standardized cultivation process to build a confluent monolayer with human aortal endothelial cells on xenogenous scaffolds. Pre-tested dynamic cultivation conditions in flow slides with pulsatile flow (1 Hz) representing arterial wall conditions were transferred to a newly designed multi-featured rotational bioreactor system. The medium was thickened with 1% methyl cellulose simulating a non-Newtonian fluid comparable to blood. Computational fluid dynamics was used to estimate the optimal volume flow and medium distribution inside the bioreactor chamber for defined wall-near shear stress levels. Flow measurements were performed during cultivation for constant monitoring of the process. Three decellularized porcine arteries were seeded and cultivated in the bioreactor over six days. 1% MC turned out to be the optimal percentage to achieve shear stress values ranging up to 10 dyn/cm2. Vascular endothelial cells formed a continuous monolayer with significant cell alignment in the direction of flow. The presented cultivation protocol in the bioreactor system thus displays a promising template for graft endothelialization and cultivation. Therefore, establishing a key step for future tissue-engineered vascular graft development with a view towards clinical application

Mobile Corona-Analytik made in Hannover : Universitäre Forschungslabore im Einsatz zur Pandemiebekämpfung

An der Leibniz Universität Hannover wurden in enger Kooperation mit dem NIFE und der Medizinischen Hochschule Hannover mobile SARS-CoV-2 Teststationen entwickelt und betrieben. Dank dieses Projekts konnten wichtige Bereiche öffentlicher Institutionen, medizinischer Einrichtungen und kritischer Infrastruktur im südlichen Niedersachsen ihren Betrieb fortführen und Forschungsfragen unter anderem zur Verbreitung des Corona-Virus untersucht werden

Lebensretter Nierentransplantation : Zur Entwicklung von Schnelltests, die eine frühzeitige Abstoßung erkennen

Für eine eindeutige Diagnostik nach einer Nierentransplantation sind bisher schmerzhafte Biopsien notwendig. Wissenschaftlerinnen vom Institut für Technische Chemie arbeiten in Kooperation mit Sartorius und der Fassisi GmbH an Schnelltests, die ohne Eingriff in den Körper spezifische und immunologisch bedeutsame Biomarker identifizieren können

Smart multifunctional nanoparticles in nanomedicine

Recent advances in nanotechnology caused a growing interest using nanomaterials in medicine to solve a number of issues associated with therapeutic agents. The fabricated nanomaterials with unique physical and chemical properties have been investigated for both diagnostic and therapeutic applications. Therapeutic agents have been combined with the nanoparticles to minimize systemic toxicity, increase their solubility, prolong the circulation half-life, reduce their immunogenicity and improve their distribution. Multifunctional nanoparticles have shown great promise in targeted imaging and therapy. In this review, we summarized the physical parameters of nanoparticles for construction of "smart" multifunctional nanoparticles and their various surface engineering strategies. Outlook and questions for the further researches were discussed. © 2016 by De Gruyter

Low impact of regular PCR testing on presence at work site during the COVID-19 pandemic: experiences during an open observational study in Lower Saxony 2020-21

Background: Since social distancing during the COVID-19-pandemic had a profound impact on professional life, this study investigated the effect of PCR testing on on-site work. Methods: PCR screening, antibody testing, and questionnaires offered to 4,890 working adults in Lower Saxony were accompanied by data collection on demographics, family status, comorbidities, social situation, health-related behavior, and the number of work-related contacts. Relative risks (RR) with 95 % confidence intervals were estimated for the associations between regular PCR testing and other work and health-related variables, respectively, and working on-site. Analyses were stratified by the suitability of work tasks for mobile office. Results: Between April 2020 and February 2021, 1,643 employees underwent PCR testing. Whether mobile working was possible strongly influenced the work behavior. Persons whose work was suitable for mobile office (mobile workers) had a lower probability of working on-site than persons whose work was not suitable for mobile office (RR = 0.09 (95 % CI: 0.07 – 0.12)). In mobile workers, regular PCR-testing was slightly associated with working on-site (RR = 1.19 (0.66; 2.14)). In those whose working place was unsuitable for mobile office, the corresponding RR was 0.94 (0.80; 1.09). Compared to persons without chronic diseases, chronically ill persons worked less often on-site if their workplace was suitable for mobile office (RR = 0.73 (0.40; 1.33)), but even more often if their workplace was not suitable for mobile office (RR = 1.17 (1.04; 1.33)). Conclusion: If work was suitable for mobile office, regular PCR-testing did not have a strong effect on presence at the work site. Trial registration: An ethics vote of the responsible medical association (Lower Saxony, Germany) retrospectively approved the evaluation of the collected subject data in a pseudonymized form in the context of medical studies (No. Bo/30/2020; Bo/31/2020; Bo/32/2020)

Heilen durch Licht : Der Einsatz optogenetischer Proteinexpression bei Cochlea-Implantaten

Cochlea-Implantate (CI) werden bei Menschen, die kaum oder gar nicht mehr hören können, in die Hörschnecke eingesetzt. Die anschließende Heilung ist entscheidend für den Erfolg der Operation. Das Institut für Technische Chemie (TCI) erforscht im Rahmen des Exzellenzclusters „Hearing4all“ wie die Einheilung von Cochlea- Implantaten mittels lichtgesteuerter Modulation zellulärer Funktionen verbessert werden kann