An Intelligent and Efficient Workflow for Path-Oriented 3D Bioprinting of Tubular Scaffolds.

Modern 3D printing is a valuable tool for tissue engineering (TE), and the fabrication of complex geometries such as tubular scaffolds with adaptable structure, for example, as replacements for intestines, bronchi, esophagus, or vessels, could contribute to standardized procedures in the future of regenerative medicine. However, high-precision bioprinting of scaffolds for tubular TE applications remain a major challenge and is an arduous endeavor with currently available three-axis bioprinters, which are limited to planar, layer-by-layer printing processes. In this work, a novel, straightforward workflow for creating toolpaths and command sets for tubular scaffolds is presented. By combining a custom software application with commercial 3D design software, a comparatively large degree of design freedom was achieved while ensuring ease of use and extensibility for future research needs. As a hardware platform, two commercial 3D bioprinters were retrofitted with a rotary axis to accommodate cylindrical mandrels as print beds, overcoming the limitations of planar print beds. The printing process using the new method was evaluated in terms of the mechanical, actuation, and synchronization characteristics of the linear and rotating axes, as well as the stability of the printing process. In this context, it became clear that extrusion-based printing processes are very sensitive to positioning errors when used with small nozzles. Despite these technical difficulties, the new process can produce single-layer, multilayer, and multimaterial structures with a wide range of pore geometries. In addition, extrusion-based printing processes can be combined with melt electrowriting to produce durable scaffolds with features in the micrometer to millimeter range. Overall, the suitability of this setup for a wide range of TE applications has thus been demonstrated.

Mobile SARS­CoV­2 screening facilities for rapid deployment and university-based diagnostic laboratory.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a public crisis. Many medical and public institutions and businesses went into isolation in response to the pandemic. Because SARS-CoV-2 can spread irrespective of a patient's course of disease, these institutions' continued operation or reopening based on the assessment and control of virus spread can be supported by targeted population screening. For this purpose, virus testing in the form of polymerase chain reaction (PCR) analysis and antibody detection in blood can be central. Mobile SARS-CoV-2 screening facilities with a built-in biosafety level (BSL)-2 laboratory were set up to allow the testing offer to be brought close to the subject group's workplace. University staff members, their expertise, and already available equipment were used to implement and operate the screening facilities and a certified diagnostic laboratory. This operation also included specimen collection, transport, PCR and antibody analysis, and informing subjects as well as public health departments. Screening facilities were established at different locations such as educational institutions, nursing homes, and companies providing critical supply chains for health care. Less than 4 weeks after the first imposed lockdown in Germany, a first mobile testing station was established featuring a build-in laboratory with two similar stations commencing operation until June 2020. During the 15-month project period, approximately 33,000 PCR tests and close to 7000 antibody detection tests were collected and analyzed. The presented approach describes the required procedures that enabled the screening facilities and laboratories to collect and process several hundred specimens each day under difficult conditions. This report can assist others in establishing similar setups for pandemic scenarios.

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.

Automated Bioreactor System for the Cultivation of Autologous Tissue-Engineered Vascular Grafts.

In an aging society, diseases associated with irreversible damage of organs are frequent. An increasing percentage of patients requires bioartificial tissue or organ substitutes. Tissue engineering products depend on a well-defined process to ensure successful cultivation while meeting high regulatory demands. The goal of the presented work is the development of a bioreactor system for the cultivation of tissue-engineered vascular grafts (TEVGs) for autologous implantation and transition from a lab scale setup to standardized production. Key characteristics include (i) the automated reliable monitoring and control of a wide-range of parameters regarding implant conditioning, (ii) easy and sterile setup and operation, (iii) reasonable costs of disposables, and (iv) parallelization of automated cultivation processes. The presented prototype bioreactor system provides comprehensive physiologically conditioning, sensing, and imaging functionality to meet all requirements for the successful cultivation of vascular grafts on a productional scale.